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The effects of XanthigenTM in the weight management of obese premenopausal women with non-alcoholic fatty liver disease and normal liver fat
Abstract
To investigate the effects of Xanthigen (brown marine algae fucoxanthin + pomegranate seed oil (PSO)) on body weight, body fat, liver lipids, and blood biochemistry; and Xanthigen and its individual components on resting energy expenditure (REE) in obese, non-diabetic female volunteers with non-alcoholic fatty liver disease (NAFLD) and normal liver fat (NLF) content.
Sixteen-week, double-blind, randomized, placebo-controlled study. Food record data, body composition, REE (only 41 volunteers with NAFLD) and blood sample analysis were assessed weekly for 16 weeks in 151 non-diabetic, obese premenopausal women with liver fat content above 11% (NAFLD) n = 113, and below 6.5% (NLF) n = 38.
Xanthigen-600/2.4 mg (300 mg PSO + 300 mg brown seaweed extract containing 2.4 mg fucoxanthin) resulted in statistically significant reduction of body weight (5.5 +/- 1.4 kg NAFLD group and 4.9 +/- 1.2 kg NLF group, p < 0.05), waist circumference (NAFLD group only), body (3.5 +/- 1.9 kg NAFLD group, p < 0.001; 3.6 +/- 0.7 kg NLF group, p < 0.05) and liver fat content, liver enzymes (NAFLD group only), serum triglycerides and C-reactive protein. Weight loss and reduction in body and liver fat content occurred earlier in patients with NLF than in patients with NAFLD. Fucoxanthin (> 2.4 mg) and Xanthigen-400/1.6 mg (200 mg PSO + 200 mg brown seaweed extract containing 1.6 mg fucoxanthin) significantly increased REE in NAFLD subjects compared to placebo.
Xanthigen promoted weight loss, reduced body and liver fat content, and improved liver function tests in obese non-diabetic women. Xanthigen and Fucoxanthin also increased REE. This product may be considered a promising food supplement in the management of obesity.
... These include skin inflammation (Rodrıǵuez-Luna et al., 2018;Spagolla Napoleão Tavares et al., 2020), ulcerative colitis (Yang et al., 2020), and contact hypersensitivity (Sakai et al., 2011). It has also been a research hotspot for its anti-diabetic (Maeda et al., 2007;Sakai et al., 2011;Kong et al., 2019) and anti-obesity (Abidov et al., 2010;Hu et al., 2012;Hitoe and Shimoda, 2017;Gille et al., 2019;Koo et al., 2019) efficacy. Non-alcoholic steatohepatitis (Takatani et al., 2020;Shih et al., 2021;Ye et al., 2022), Alzheimer's disease Xiang et al., 2017;Alghazwi et al., 2019;Shih et al., 2021;Yang et al., 2021;, and other biological activities [e.g., antiviral (Tsushima et al., 1995;Tamama, 2021)] have also been proven. ...
... The study showed a significant reduction in relative body weight and BMI with no observed abnormalities (Hitoe and Shimoda, 2017). Another clinical trial revealed an increase in resting energy expenditure (REE), in obese patients who were supplemented with 4 mg of fucoxanthin per day (Abidov et al., 2010). It was observed that 8 mg fucoxanthin demonstrated an even higher REE expenditure, suggesting that its efficacy may be dose-dependent (Abidov et al., 2010). ...
... Another clinical trial revealed an increase in resting energy expenditure (REE), in obese patients who were supplemented with 4 mg of fucoxanthin per day (Abidov et al., 2010). It was observed that 8 mg fucoxanthin demonstrated an even higher REE expenditure, suggesting that its efficacy may be dose-dependent (Abidov et al., 2010). ...
Background
Fucoxanthin is a carotenoid found in seaweed. Its unique chemical structure gives it a variety of properties. Thus fucoxanthin have attracted the attention of companies and researchers.
Methods
Scientific papers were collected from the database. Duplicates and unavailable literature were excluded first. Then the remaining literature was categorized for referencing in the review.
Results
This article contains a summary of the microalgae species producing fucoxanthin and their progress in breeding and cultivation modes. Additionally, the review summarized the progress of research on physiological activities and organized the experimental models used in these studies.
Conclusions
These present findings may provide information for the upstream production of fucoxanthin from algal species selection to process optimization. The analysis of the physiological activity results will help advance subsequent physiological and biochemical experiments. Furthermore, it intends to pique researchers’ enthusiasm for fucoxanthin and enrich related research data to accelerate the development of this natural product.
... kg reported in previous studies. [15][16][17] Consequently, a significant reduction in BMI was also reported in those patients. Fucoxanthin may regulate BW gain and fat accumulation in adipose tissue because it prevents adipocyte differentiation from brown adipose tissue (BAT) to white adipose tissue, which has greater proinflammatory activity. ...
... This result coincides with previous reports in populations with overweight and obesity. [15][16][17] These significant findings suggest that fucoxanthin almost doubles the effect of physical exercise and a low-sodium diet on normotensive subjects and it has a marginally superior effect in hypertensive patients with the same lifestyle changes. 21 The mechanism for blood pressure improvement is not yet clear. ...
... No changes in FPG or in 2-h postload plasma glucose levels were observed in any group. These results are in line with previous clinical trials [15][16][17] ...
The aim of this study was to evaluate the effect of fucoxanthin on metabolic syndrome (MetS), insulin sensitivity, and insulin secretion. A randomized, double-blind, placebo-controlled clinical trial was conducted in 28 patients diagnosed with MetS. Patients were randomly assigned to receive 12 mg of fucoxanthin or placebo once a day for 12 weeks. Before and after the intervention, the components of MetS, insulin sensitivity (Matsuda index), first phase of insulin secretion (Stumvoll index), and total insulin secretion were evaluated during a 2-h oral glucose tolerance test. After fucoxanthin administration, significant differences were observed in body weight (BW) (80.6 ± 11.2 vs. 79.16 ± 12.3 kg, P < .01), body mass index (BMI) (31.1 ± 3.6 vs. 30.3 ± 3.7 kg/m2, P < .01), waist circumference (WC) (101.2 ± 9.1 vs. 98.9 ± 9.3 cm, P < .01), systolic blood pressure (SBP) (126.1 ± 10.3 vs. 120.8 ± 9.7 mmHg, P < .01), diastolic blood pressure (DBP) (81.5 ± 6.5 vs. 78.6 ± 6.3 mmHg, P < .01), triglycerides (TG) (2.2 ± 0.7 vs. 2.1 ± 0.7 mmol/L, P < .01), Stumvoll index (2403 ± 621 vs. 2907 ± 732, P < .05), and total insulin secretion (0.84 ± 0.31 vs. 1.02 ± 0.32, P < .05). In conclusion, fucoxanthin administration leads to a decrease in BW, BMI, WC, SBP, DBP, TG, as well as increase in the first phase of insulin secretion and total insulin secretion in patients with MetS. Clinical Trial Registration number: NCT03613740.
... A lot of studies confirmed the usefulness of using functional foods in the context of NAFLD treatment. Among beneficial outcomes, improvements in anthropometric measures, liver function, hepatic fat amounts, and glucose maintenance parameters can be specified [206][207][208]. To provide better clarity, we will present the composition of the given nutraceuticals and their impact on the condition of patients with NAFLD in the form of a table. ...
... The study by Abidov et al. [208] on the nutraceutical XanthigenTM revealed its antiobesity properties in obese women with NAFLD. As a factor that contributes to reductions in body fat and liver fat, it may play an essential role in the prevention and treatment of NAFLD. ...
... The authors indicate that its anti-inflammatory effect may be facilitated by weight loss. In addition, XanthigenTM increased resting energy expenditure, which may be an important driver leading to weight loss [208]. ...
There is a need to introduce standardized treatment options for non-alcoholic fatty liver disease (NAFLD) due to its global prevalence and the complications of this disease. Many studies have revealed that food-derived substances may be beneficial in dealing with this disease. Therefore, this review aims to evaluate the recently published studies on the food-derived treatment options for NAFLD. A comprehensive search of the PubMed database using keywords such as “NAFLD”, “nutrition”, “food”, “derived”, “therapy”, and “guidelines” yielded 219 relevant papers for our analysis, published from 2004 to 2023. The results show the significant benefits of food-derived treatment in NAFLD therapy, including improvements in liver histology, hepatic fat amounts, anthropometric measures, lipid profile, and other metabolic measures. The availability of the substances discussed makes them a significant adjuvant in the treatment of this disease. The usefulness of Viusid as additional therapy to diet and physical activity should be emphasized due to improvements in liver histology; however, many other substances lead to a decrease in liver fat amounts including, e.g., berberine or omega-3 fatty acids. In addition, the synbiotic Protexin seems to be useful in terms of NAFLD treatment, especially because it is effective in both obese and lean subjects. Based on the latest research results, we suggest revising the therapeutic recommendations for patients suffering from NAFLD.
... Outro ensaio, comparou os dados obtidos com humanos com os dados obtidos com ratos e concluíram que administrando uma dose sete vezes superior em humanos, a concentração de fucoxantinol detectada no plasma alcançava apenas um terço ou metade daquela encontrada em ratos com doses inferiores administradas. Outros estudos obtiveram resultados semelhantes, mostrando que um suplemento dietético diário de 0,024 mg de fucoxantina por quilo foi suficiente para reduzir o tecidos adiposo branco abdominal em humanos [73] enquanto para alcançar os mesmos resultados em ratos obesos foi necessária uma dose diária superior a 100 mg de fucoxantina por quilo [74,75]. A menor concentração de fucoxantina ou fucoxantinol detectada ou as altas doses necessárias para ter efeitos em ratos podem ocorrer devido ao metabolismo mais rápido característico de animais pequenos e com ciclos de vida curtos, bem como às taxas de absorção diferenciadas de moléculas semelhantes à fucoxantina de cada espécie [76]. ...
... A etapa de esterificação, além de permitir o transporte e distribuição da fucoxantina, transforma-a numa molécula apolar de maior biodisponibilidade, reduzindo assim os seus possíveis efeitos tóxicos e protegendo o organismo [64,65]. Conforme explicado na seção III-B: 1 diferenças entre espécies foram observadas por poucos autores que destacaram que, para obter resultados semelhantes, os ratos necessitaram a administração de doses mais altas de fucoxantina do que os humanos [72,73,75]. A explicação das diferenças entre a dose efectiva em humanos e ratos pode dar-se por diferentes razões. ...
... The formulation of these products was made with ecological ingredients, using algae wildly recollected in a sustainable way in the Galician Coast Lines. The three products have a recommended daily dose of 32 g per day (or 4 tablespoons) which will correspond to 8 mg of daily bioactive fucoxanthin intake, which is the daily recommended dose, according to in vivo studies [73,234,235]. These formulations were created in a fine powder preparation that can be added to juices, milkshakes, smoothies, cereals, fruit bowls, soups, salads, stews, meats, fishes, desserts, sandwiches and more. ...
In recent decades, numerous marine organisms have been shown to be a promising source of compounds of interest to the food industry, such as vitamins, minerals, polyunsaturated fatty acids, peptides, phenolic compounds, pigments, etc. Algae are among these organisms and have been used as food and traditional remedies, initially in Asian countries but are currently used all around the world. In addition to its good nutritional values, the presence of bioactive compounds has drawn the attention of different areas of research and several industries with the aim of promoting its application as a sustainable raw material for the obtention of new ingredients. Taking this into account, the general objective of this doctoral thesis was to explore the potential of macroalgae from the Galician coastline as a source of bioactives, which resulted as a final purpose to define the optimal conditions for different methodologies for the extraction of fucoxanthin from Undaria pinnatifida.
In an initial screening stage, eight species of macroalgae were considered as possible sources of active compounds: Ulva rigida and Codium tomentosum from the Cholophyta group (green algae), Palmaria palmata and Porphyra purpurea from the Rodophyta group (red algae) and Himanthalia elongata, Laminaria ochroleuca, S. latissima and U. pinnatifida from the Ochrophyta group (brown algae), which are widely present on the Galician coastline and are currently used in the food industry. The chemical composition, nutritional analysis and antioxidant and anti-inflammatory properties of these species were analyzed, revealing a great variability between species and groups. However, the four species of brown algae showed a higher extraction yield, which is a fundamental parameter for the design of subsequent industrial processes. Based on this, brown algae were selected as the study group for future analyses.
In a second stage, it was decided to assess the potential of algae group as a source of bioactive compounds. For this a few more species of brown algae were added to the ones previously used, whose use is not currently widespread, in order to increase the range of evaluation. The added species were Ascophyllum nodosum, Bifurcaria bifurcata, Fucus spiralis, Pelvetia canaliculata and Sargassum muticum, which are all species you can also find in the Galician coastline. In this study, the pigment composition and biological properties of these nine species of brown algae was carried out, using different solvents (ethanol, acetone, hexane, chloroform and ethyl acetate), in order to evaluate the suitability of each one and select the most appropriate. The pigment analysis showed the presence of a wide variety of pigments, highlighting fucoxanthin, which was found in large quantities in all studied species but specially in U. pinnatifida. This carotenoid has gained relevance for a few decades, due to its numerous biological properties, corroborated both in vitro and in vivo. In fact, it has been considered as a functional ingredient for the development of various nutraceutical products, so this molecule was selected as the target compound and the algae U. pinnatifida as the principal extraction matrix. Additionally, ethanol and acetone were able to obtain higher yields, and they are both suitable to be used in the food industry, so they were chosen as extraction solvents.
Once the target compound, matrix, and extraction solvents had been selected, the next step was to design a rapid method HPLC-DAD to quantify fucoxanthin from a large number of samples, in a simple way. This method was used for the optimization stage of the fucoxanthin extraction methods. Firstly, two kinetic studies were carried out to compare the efficiency of both solvents in fucoxanthin extraction. Based on the results, the most efficient solvent for its extraction was ethanol, which is considered a green solvent, suitable for the development of respectable industrial processes with the environment.
Next, the extraction of fucoxanthin from U. pinnatifida was also carried out using innovative extraction techniques as MAE and UAE. This, methodology was used to determine on a laboratory scale, the conditions that allowed the best fucoxanthin extraction performance based on the previously selected factors. In the optimization, variables like power, extraction time and solvent concentration were evaluated, using a response surface methodology. This procedure was used with two different technologies: MAE and UAE, to contrast its effectiveness, and they were compared with a conventional method using a standard SAE. The results showed that through UAE technology the obtained yield was much higher than the one obtained with conventional techniques and also the ones reported in literature.
Lastly, once the best conditions for extraction were determined and the kinetic of fucoxanthin’s extraction was known, the results were discussed with an algae factory and a pilot plant was designed, according to their preferences and specifications, to obtain extracts rich in fucoxanthin at a larger scale. In the pilot plant designed, the alga is washed, desiccated and pulverized preparing it to the extraction in an industrial reactor. After the extraction, the content is filtered, obtaining an extract rich in fucoxanthin, which is finally dehydrated and stored. The final extract was later incorporated into a food product with added nutritional value.
... All of the studies were conducted on a small sample (N < 100) with a randomized controlled trial (RCT) type of study conducted on NAFLD patients who were not diagnosed with diabetes or undergoing antidiabetic treatment or treatment with other medications. Most of the studies were conducted in Asia [25][26][27][28] and one study was from Europe [29]. The study focused on an adult population between 36 and 59 years of age with the majority of the sample being women. ...
... All studies showed significant improvement of liver injury in the intervention group regardless of the type of intervention and its combination with placebo The effects of seaweed supplementation consumption for improvement of liver injury in patients with non-alcoholic fatty liver disease: a systematic review Record exclude: -not full text -review or systematic review -meta-analysis -case study Exclude the following: -not in English -multiple report on the same study -main outcome not liver enzyme -study not conducted in humans (Table 2). Three studies [27][28][29] used extracts from brown seaweed (fucoxanthin and fucoidan) with different study durations (12 weeks vs. 16 weeks) which can reduce liver enzyme levels. Two of the three studies [27,28] used two different extraction combinations which resulted in different potencies, but the extraction from brown seaweed produced a significant reduction in liver injury. ...
... In one study [27], the significant change in liver enzyme did not affect CAP, the parameter of liver steatosis. One study [29] reported that there is no adverse effect from all participants while other studies did not report the adverse effect. Details of secondary outcomes are presented at Table 2. ...
Seaweed is a food that is widely consumed by Asian people and has many health benefits, including lipid and glycemic reduction, but the effect of seaweed on non-alcoholic fatty liver disease (NAFLD) has not been widely discussed. This study aims to compare the effect of seaweed consumption on improving liver injury in NAFLD patients. The primary outcome is the change of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and g-glutamyl transferase [GGT]), while the secondary outcome includes body weight, waist circumstance, body mass index (BMI), lipid profile, insulin level, and insulin sensitivity and any related metabolic indicators. There was significant liver improvement in the intervention group, but some parameters from secondary outcomes showed no significant effect. Further studies with larger and heterogeneous populations are still needed to confirm the effectiveness of seaweed supplementation in NAFLD patients.
... Fucoxanthinol was found in plasma at a concentration of 0.8 nM by Asai et al. (2008)), following one week of daily consumption of the brown seaweed wakame (Undaria pinnatifida), which contains 6.1 mg fucoxanthin. Abidov et al. (2010) conducted a 16-week clinical research with 151 obese women using xanthigen, a dietary supplement made of brown seaweed extract with 2.4 mg of fucoxanthin and pomegranate seed oil. The results showed that patients with body mass indices (BMI) greater than 30 kg/m 2 experienced significant weight loss and a reduction in belly circumference (Abidov et al., 2010). ...
... Abidov et al. (2010) conducted a 16-week clinical research with 151 obese women using xanthigen, a dietary supplement made of brown seaweed extract with 2.4 mg of fucoxanthin and pomegranate seed oil. The results showed that patients with body mass indices (BMI) greater than 30 kg/m 2 experienced significant weight loss and a reduction in belly circumference (Abidov et al., 2010). A study was carried out by Hashimoto et al. (2012) on 18 human participants who took an oral kombu extract containing 31 mg of fucoxanthin. ...
Fucoxanthin is a unique carotenoid present in brown seaweed due to the presence of an allenic bond in its structure. Its chemical composition consists of a central core that is cyclic, many conjugated double bonds, and several functional groups. Fucoxanthin plays a critical role in photosynthesis, absorbing light energy and transferring it to chlorophyll a. It has been demonstrated to have a variety of health advantages as well as protective effects against conditions including diabetes, liver cirrhosis, obesity, and malignant cancer, etc. Therefore, fucoxanthin can be employed as a strong pharmaceutical and dietary components to stop the spread of a wide array of infectious disorders. The present review focuses on the most recent research related to the pharmaceutical properties of fucoxanthin including antibacterial, antioxidant, anti-inflammatory, skin-protective, anti-obesity, anti-diabetic, and other qualities, including bioavailability and stability traits. This review seeks to support future biochemical research in order to create new pharmaceutical and dietary supplements that work with fucoxanthin and its many metabolites.
... The Fx molecule (C 42 H 58 O 6 , 658.9 g/mol) comprises a polyene chain, an allenic bond, a 5,6-monoepoxide group, and a carbonyl group (Supplementary Figure S1). Toxicological and interventional studies have suggested that Fx is a safe compound with no adverse effects in humans or rodents [15][16][17][18][19][20]. Fx is easily converted into deacetylated fucoxanthinol (FxOH) in the intestines of humans and mice and FxOH is one of the main metabolites detected in blood and tissues [21,22]. ...
... However, data on the clinical safety of Fx in humans are scarce. Oral administration of Fx-rich algal extracts (1.0−8.0 mg Fx/human/day for 1−4 months) has been shown to exert anti-obesity and anti-diabetes effects in humans without serious adverse effects [18][19][20]. Thus, there is a need for further investigations to determine the safe dose of Fx in humans. ...
Pancreatic cancer (PC) is one of the most fatal cancers, and there is an urgent need to develop new anticancer agents with fewer side effects for the treatment of this condition. A patient-derived xenograft (PDX) mouse model transplanted with cancer tissue from patients is widely accepted as the best preclinical model for evaluating the anticancer potential of drug candidates. Fucoxanthin (Fx) is a highly polar carotenoid contained in edible marine brown algae and possesses anticancer activity. However, there is a lack of data on the effects of Fx in PDX models. We investigated the anticancer effects of Fx in PDX mice transplanted with cancer tissues derived from a patient with PC (PC-PDX) using comprehensive protein expression assay. Fx administration (0.3%Fx diet) ad libitum for 27 days significantly abrogated tumor development (0.4-fold) and induced tumor differentiation in PC-PDX mice, as compared to those in the control mice. Fx significantly upregulated the expression of non-glycanated DCN (2.4-fold), tended to increase the expressions of p-p38(Thr180/Tyr182) (1.6-fold) and pJNK(Thr183/Tyr185) (1.8-fold), significantly downregulated IGFBP2 (0.6-fold) and EpCAM (0.7-fold), and tended to decrease LCN2 (0.6-fold) levels in the tumors of the PC-PDX mice, as compared to those in the control mice. Some of the protein expression patterns were consistent with the in vitro experiments. That is, treatment of fucoxanthinol (FxOH), a prime metabolite derived from dietary Fx, enhanced non-glycanated DCN, p-p38(Thr180/Tyr182), and pJNK(Thr183/Tyr185) levels in human PC PANC-1 and BxPC-3 cells.These results suggested that Fx exerts anticancer and differentiation effects in a PC-PDX mice through alterations of some multifunctional molecules.
... Green seaweed has a protein content ranging from 10 to 26 %, according to studies. Red seaweeds with the highest protein content, such as Phorphyra tenure and Palmaria palmata, had a protein content of around 47 % [62] . There are numerous compounds isolated from various seaweed species that inhibit -glucosidase activity. ...
... Fucoidan, a watersoluble polysaccharide, inhibited the activities ofglucosidase and -amylase differently depending on the collection period and target enzyme Fucoidan extracted from A. nodosum inhibited both -glucosidase andamylase, whereas fucoidan extracted from F. vesiculosus inhibited only -glucosidase. Fucoidan from A. nodosum also reduced -amylase activity by 7 to 100 % at 5 mg/ml, with IC50 values ranging from 0.12 to 4.64 mg/ml depending on the seaweed collection period [61][62][63][64] . ...
Type 2 diabetes is a long-term disease that impairs the body's ability to process blood sugar (glucose). Insulin resistance occurs when the body either produces insufficient insulin or resists insulin. The majority of diabetes cases worldwide are Type II diabetes mellitus (T2DM), which is caused by an unhealthy diet, sedentary lifestyle, and population obesity, necessitating the search for new preventive and treatment strategies. Seaweeds contain a lot of dietary fibre, unsaturated fatty acids, and polyphenolic compounds. Seaweed bioactive components help to improve glucose tolerance while also lowering circulating lipid levels. As a result, taking seaweed supplements that are reducing the risk of type 2 diabetes complications and their composition affects type 2 diabetes.
... Washed and dried barley was roasted at 80-100 • C in a roaster (Shri Venkateshwara Industries, India) for 20-30 min and ground the barley and dried seaweed using a hammer mill (Pilot Smith India Pvt. Ltd., India). The powdered seaweed (as per RDI of Fx) [20]and barley flour were mixed in a 1:4 ratio and blended with table salt (5 %) and cumin seed powder (3 %). The blend was dispersed in warm water to form a slurry and drum dried (double drum dryer-Germany) at 110 • C by steam condensing (230 kPa). ...
... Group 3 received lowdose LPS with anti-inflammatory Food (LPS + AIF) (63 mg/kg of AIF, was gavaged in water) and group 4 animals were administered LPS and Diclofenac (LPS + DF) and hence was considered the positive control group (100 μg/kg BW) intraperitoneally to LPS induced mice. The dosage of AIF (RDI of Fx, 2.3 mg/60 kg adult) and diclofenac was determined based on earlier findings [14,20]. The entire animal trial lasted for 10 weeks (Fig. 2). ...
... Another study reported the administration of fucoxanthin capsules to 115 nondiabetic, premenopausal, obese women with a liver fat composition >11% for over a period of 16 weeks [246]. One capsule with dried, brown seaweed extract (300 mg) with fucoxanthin (2.4 mg) in combination with pomegranate seed oil (300 mg) was given daily. ...
... Fucoxanthin, which is a major carotenoid observed in brown seaweeds, exhibited anti-obesity potential, particularly in obese individuals with non-alcoholic fatty liver disease and increased levels of chronic inflammation [246]. The fucoxanthin aids in the decrease of body weight through (1) improving resistance to insulin [247], (2) reduction of plasma insulin and blood glucose [248], (3) production of heat in white adipose tissue (WAT20) [247,249], (4) fatty acids oxidation, (5) causing increased resting energy expenditure, by uncoupling step during cell metabolism [250] and (6) up-regulation of mitochondrial uncoupling protein 1 (UCP1) gene expression in WAT [249]. ...
Edible algae, including seaweeds, are a source of functional food, dietary supplements, metabolites and bioactive compounds. Algal-based functional foods have potential health benefits, and their commercial value depends on their applications in the food and nutraceutical industries.
This book covers several aspects of algal-based functional foods. It informs the reader about algal cultivation techniques, environmental impact, habitat, nutraceutical potential, extraction of bioactive metabolites, functional-food composition, bio-prospection, culture-induced nutraceutical compounds, algae-based bio-packaging, algal-biorefinery, toxicity, trends and future prospects.
The editors present the topics in a research-oriented format while citing scholarly references.
This book is a comprehensive resource for anyone interested in the nutritional benefits and industrial utilization of algae as a sustainable food source.
... In animal studies, fucoxanthin results in weight reduction qualities through stimulation of mitochondrial uncoupling protein 1 (UCP1), which functions as metabolic thermogenesis to prevent excessive fat and lipid formation as well as inhibition of adipocyte differentiation. It can inhibit the glycerol-3-phosphate dehydrogenase action and downregulate peroxisome proliferator-activated receptor γ (PPARγ) which is important for the expression of the adipogenic gene [128,129]. ...
... According to Gille, Stojnic, Derwenskus, Trautmann, Schmid-Staiger, Posten, Briviba, Palou, Bonet and Ribot [130], fucoxanthin can downregulate mRNA levels of lipolysis-related genes (Lipe and Plin1), fatty acid uptake-related gene (Cd36), lipogenesis-related genes (Srebf1), and lipoprotein lipase coding (Lpl) in mice visceral WAT. In a human clinical trial by Abidov, Ramazanov, Seifulla and Grachev [129], an intake of 2.4 mg/d of fucoxanthin for 16 weeks was reported to significantly decrease body weight, body fat, waist circumference, serum triglycerides level, plasma aminotransferase enzymes level, and blood pressure level while increasing resting energy expenditure (REE). Stimulation of REE was partly responsible for the loss of body weight and body fat reduction, combined with wide anti-inflammatory and metabolism-normalising activities. ...
Fucoxanthin is an algae-specific xanthophyll of aquatic carotenoid. It is prevalent in brown seaweed because it functions as a light-harvesting complex for algal photosynthesis and photoprotection. Its exceptional chemical structure exhibits numerous biological activities that benefit human health. Due to these valuable properties, fucoxanthin’s potential as a potent source for functional food, feed, and medicine is being explored extensively today. This article has thoroughly reviewed the availability and biosynthesis of fucoxanthin in the brown seaweed, as well as the mechanism behind it. We included the literature findings concerning the beneficial bioactivities of fucoxanthin such as antioxidant, anti-inflammatory, anti-obesity, antidiabetic, anticancer, and other potential activities. Last, an additional view on its potential as a functional food ingredient has been discussed to facilitate a broader application of fucoxanthin as a promising bioactive compound.
... Studies by the National Institutes of Health (NIH) have further revealed that HRT may increase the risk of breast cancer, venous thromboembolism, coronary artery disease, and stroke [21,22]. Thus, there is an urgent need to develop natural or composite agents capable of mitigating menopausal symptoms and preventing chronic diseases, and current research is exploring these possibilities [23,24]. For instance, Quynh et al. reported the estrogenic activity of silkworm extracts obtained using 30% ethanol [25]. ...
Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.
... Antioxidant properties, neuroprotective properties and protection against chronic diseases are just a few of the health advantages of microalgal pigments and carotenoids (Pangestuti and Kim 2011). Another microalgal pigment with beneficial nutritional properties for managing weight is called fucoxanthin (Abidov et al. 2010). Proteins derived from microalgae also play a major role in the nutraceutical characteristics of microalgal dietary supplements, maybe because of their therapeutic potential in treating a range of chronic diseases. ...
Microalgae, tiny photosynthetic organisms found in diverse aquatic environments, have emerged as promising sources of bioactive compounds with potential health benefits having medicinal, anticancerous and pharmaceutical applications. The invention of several genetic tools along with omics studies such as proteomics, genomics, metabolomics and transcriptomics has made it easier to understand the proper metabolic pathways as well as downstream processes. The microbial omics approach has transformed our understanding of human health. It enables the comprehensive analysis of microalgal communities and their functional capabilities, providing insights into disease mechanisms and potential therapeutic targets. In this chapter, we will enlighten the various components of microalgal origin having direct or indirect role on human health. Several cyanobacteria-derived secondary metabolites having pharmaceutical applications will also be discussed. It is also important to highlight the latest advancements in molecular alterations and how they can be used in algae to produce high-yield bioactive chemicals that are suitable for human consumption by enhancing algal target strains. For the purpose of directing the improvement of culture conditions, understanding the molecular pathways of bioactive substances under abiotic stress is of enormous practical importance. Such knowledge facilitates the development of personalised interventions and therapeutics to enhance human health outcomes. By continuing to advance these techniques, we can further unlock the potential of the microbiome in improving human health.
... Recent investigations have identified that commercially available thermogenic supplements and ingredients typically contained in such products positively induce acute the inhibition of fat cell proliferation and improvements in glucose control in diabetic populations [21]. In a previous randomized, placebo-controlled, clinical trial, significant reductions in body weight, waist circumference and body fat were observed with chronic supplementation of fucoxanthin [22]. ...
There has been a rise in popularity of “stimulant-free” or caffeine-free fat loss supplements, but it is not well understood whether those fat loss supplements are effective at enhancing thermogenesis without caffeine’s influence. The purpose of this study was to examine the effects of a caffeinated and non-caffeinated commercially available fat loss supplement on resting energy expenditure (REE), hunger, and hemodynamic variables in healthy adults. Twenty-five healthy male and female participants completed three separate laboratory visits after overnight fasts. Baseline assessments of REE, subjective hunger, heart rate (HR), and blood pressure (BP) were followed by ingestion of a caffeinated (Phoenix, Legion®; CAF), non-caffeinated (Phoenix Caffeine-Free, Legion®; NCAF), or placebo (PL) fat loss supplement. REE, hunger, HR, and BP assessments were repeated at 60-, 120-, and 180-min post-ingestion. CAF, but not NCAF, significantly elevated REE greater than PL at all time points (p < 0.05). NCAF significantly reduced hunger compared to CAF and PL at the 120-min time point (p = 0.006). CAF significantly increased diastolic BP 60-min post-ingestion and significantly increased systolic BP 120- and 180-min post-ingestion compared to NCAF and PL. Further research is warranted with respect to investigating non-caffeinated ingredients and their effects on REE.
... The bioactive polyphenolic compounds of pomegranate appear to play a crucial role also in reducing the body weight and improving the body composition in overweight or obese subjects [67,68]. In fact, a study conducted on obese non-diabetic premenopausal female patients, who daily assumed 300 mg of PSO, for 16 weeks, showed a significant reduction in body weight, waist circumference and liver fat content, as well as in serum triglycerides and C-reactive protein (CRP) levels, of treated women compared to control group [69]. ...
Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, Middle East and USA areas. While in the ancient time pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, up to consider pomegranate as a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs) and its consumption appears to exert numerous healthy beneficial effects, in particular, in several pathological conditions, namely in patients affected by metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and in dentistry represents a promising field, as it could permit the development of innovative natural adjuvant therapies, able to empower the standard pharmaceutical therapies.
... The aforementioned findings provide additional evidence for this result [25,26], indicating that FUC can regulate ALT and AST activities, thereby reducing PAC-induced liver injury. Very few published studies have examined the effects of fucoxanthin on patients with liver injury [27][28][29]. A randomized, placebo-controlled clinical trial with a 24-week follow-up was previously conducted on 42 patients [30]. ...
Paracetamol or acetaminophen (PAC) is a commonly used analgesic and antipyretic drug. It has been shown that overdoses beyond the therapeutic range can cause hepatotoxicity and acute liver injury. The most common cause of drug-induced liver injury (DILI) in Saudi Arabia and worldwide is paracetamol overdose. Fucoxanthin (FUC) is an allenic carotenoid that is found in edible brown seaweeds, and it has antioxidant and anti-inflammatory effects. Several studies have shown the potential therapeutic effects of FUC in diabetes, cancers, and inflammatory disorders. This study aims to investigate the protective effect of FUC against PAC-induced acute liver injury in rats. FUC was administered (100, 200, and 500 mg/kg, p.o.) for 7 days, and then the liver injury was induced by the administration of PAC (2000 mg/kg, oral). Blood and liver tissue samples were collected from PAC-positive untreated, treated, and negative control rats. Biochemical and inflammatory parameters in the blood were measured. In addition, RT-PCR, Western blotting, and immunohistochemistry were performed for liver tissue. The serum levels of liver biomarkers (ALT, AST, and ALP) increased after PAC-induced liver toxicity; FUC-treated rats showed lower levels compared to the positive control. There was an increase in the expression of TNF-α, IL-1, IL-6, NF-kB, INF-γ, and iNOS and a decrease in IL-10, IL-22, and IL-10R expression after the FUC treatment of injured liver rats. For the hepatic inflammation and PAC-toxicity-induced oxidative stress genes and proteins, FUC-treated rats (100, 200, and 500 mg/kg) showed a reduction in the expression of oxidative stress genes. These results showed that FUC protected the liver against PAC-induced injury through antioxidant and anti-inflammatory actions. However, further clinical studies are required to confirm the findings.
... But after menopause, estrogen levels in a female's body drop, which can also increase a female's risk of alcoholic liver disease (Park et al., 2006;An, 2022). Obesity has also been linked to alcoholic liver disease, a condition in which an overweight person has high levels of body fat, which burdens the liver and makes it vulnerable to damage from alcohol and other harmful substances (Abidov et al., 2010). In addition, obesity can cause metabolic syndrome, a syndrome that includes high blood pressure, high blood sugar, triglycerides and low HDL cholesterol, all of which can have an adverse effect on the liver. ...
... 66,74 Despite the recent advances in successfully modulating miRNA levels to combat miRNA-related diseases, the outcome is invariably associated with severe adverse effects that force its discontinuation in clinical settings. 66,74 Due to this uncertainty in pharmacologic management, advances are being made in an organic treatment approach to halt the progression of NAFLD via targeting microRNAs, 61 such as the inclusion of extra virgin olive oil combined with a low caloric diet, 61,75 curcumin, 61,63,76 Xanthigen, a blend of Wakame (brown seaweed) and pomegranate seed oil, 61,77 and soy milk. 61,78 We advise further investigation into synthetic and natural compounds for the treating NAFLD via targeting miRNAs. ...
Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver condition that affects people who do not overconsume alcohol. Uncertainties exist over how microRNAs (miRNAs) in the blood and liver relate to NAFLD. The aim of this narrative review was to investigate the role of miRNAs in the onset and progression of non-alcoholic steatohepatitis (NASH) from NAFLD, and explore their potential as diagnostic tools and treatment targets for NAFLD patients. Liver miRNA-34a levels were found to accurately represent the degree of liver damage, with lower levels suggesting more damage. In patients with NAFLD and severe liver fibrosis, higher levels of miRNA-193a-5p and miRNA-378d were found. Moreover, miRNA-34a, miRNA-122, and miRNA-192 levels might aid in differentiating NASH from NAFLD. Similar to this, miRNA-21 and miRNA-27 levels in rats were able to distinguish between steatosis and steatohepatitis. High-fat diets enhanced the expression of 15 distinct miRNAs in rats, and there were substantial differences in the miRNA expression patterns between obese and lean people. The results from the present review imply that miRNA microarrays and sequencing may be helpful diagnostic tools, and miRNAs may be a possible treatment target for patients with NAFLD.
... Fucoxanthin treatment in diabetes with hypertension rat has prevented these secondary complications. Fucoxanthin is known to protect liver function against oxidative stress, spontaneous liver tumorigenesis and non-alcoholic fatty liver disease [41][42][43][44]. Also, fucoxanthin is known to protect heart against various toxicities [4,30,31]. ...
In a previous study from our laboratory, fucoxanthin purified from brown algae, Sargassum wightii Greville has found to exhibit antioxidant activity and inhibition of angiotensin-I-converting enzyme (ACE) in vitro. The present study aims in understanding the protective effect of fucoxanthin purified from S. wightii against diabetes with hypertension in in vivo. Diabetes and hypertension were induced in rat by streptozotocin and sodium chloride treatment, respectively. In diabetes with hypertension rat, the blood pressure was increased along with hyperglycemia. Administration of fucoxanthin significantly reduced the blood pressure and ACE activity in diabetes with hypertension rat. Furthermore, administration of fucoxanthin significantly reduced the hyperglycemic state. The activity of various enzymes in the liver (hexokinase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase and fructose-1, 6-phosphatase) and serum (creatine kinase) were normalized to that of control level. The level of glycogen, glycoprotein component and lipid profile were equivalent to control level by fucoxanthin administration in diabetes with hypertension rats. Fucoxanthin ameliorated the oxidative stress by preserving the endogenous antioxidant levels in diabetes with hypertension rats. Also, the pancreatic histological integrity was similar to that of control level in diabetes with hypertension rats by fucoxanthin treatment. Altogether, fucoxanthin showed dual antidiabetic and antihypertensive activity in vivo.
... The composition of the oil content of the seed oils of 25 pomegranate varieties from two different regions of Iran has ranged from 6.6% to 19.3% with linolenic acid (C18:3) as the major fatty acid (31.8% to 86.6%), followed by linoleic [0.7% to 24.4%] and oleic acid [0.4% to 17.4%] [13]. Here are some properties of punicic acid: antidiabetic and antiobesity (14), hypolipidemic [15], anti-inflammatory [16], anticancer [17], anti-oxidative and hypolipemic activities [18[, protection against sodium arsenite toxicity [19], anti-nephrotoxic [20], lipid peroxidation [21], antiestrogen on estrogen receptors [22], lipid-lowering effects and cause of significant fat loss in human subjects [23]. As noted, pomegranate seed oil is very rich in punicic acid, a known inhibitor of prostaglandin biosynthesis, specifically by inhibiting cyclooxygenase (Cox 1 and Cox 2) and lipoxygenase [24]. ...
Gastric ulcers have affected a large number of people around the world. Generally, the development of this disease results from an imbalance between mucosal defense mechanisms such as mucosal, bicarbonate, prostaglandin, and mucosal blood flow, and degrading factors including acid and pepsin in the luminal level of the gastric mucosa. Among these factors, two major causes of gastric ulcer and gastric ulcer healing are H. pylori infection and long-term use of nonsteroidal anti-inflammatory drugs (NSIADs) 1. Due to the side effects of these drugs (such as gastrointestinal complications), the use of alternative drugs is unavoidable and, given that the herbal remedies have little complications, the use of medicinal herbs for the treatment of this disease was also noted. Nigella sativa (Family Ranunculaceae) is a widely used medicinal plant throughout the world. Seeds and oil have a long history of folklore usage in various systems of medicines and food. In Islamic literature, it is considered as one of the greatest forms of healing medicine. It has been recommended for using on regular basis in Tibb-e-Nabwi (Prophetic Medicine). It has been widely used as antihypertensive, liver tonics, diuretics, digestive, anti-diarrheal, appetite stimulant, analgesics, anti-bacterial and in skin disorders, antidiabetic, anticancer, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, bronchodilator, hepato-protective, renal protective, gastro-protective, antioxidant properties, etc. Due to its miraculous power of healing, Nigella sativa has got the place among the top ranked evidence based herbal medicines. In this research, the effect of alcoholic extract of Nigella sativa L. (AENS) 2 on the expression of Cycloxygenase-1 (COX-1) 3 gene on KATO III cells and Cycloxygenase-2 (COX-2) 4 gene on bovine fibroblast-like synoviocyte (BFLSc) 5 was investigated.
... Key records such as food habits, body composition, resting energy expenditure (REE) with 41 volunteers with fatty liver disease and analysis of blood samples were conducted over 16 weeks in 151 non-diabetic and obese premenopausal women with liver fat content above 11%. The results showed that Xanthigen at a dose of 300 mg PSO + 300 mg brown algae extract (2.4 mg fucoxanthin) was able to reduce body weight, waist circumference, and liver fat content as well as liver enzymes, serum triglycerides and C-reactive protein compared to placebo (Abidov et al. 2010). ...
Nonalcoholic fatty liver disease (NAFLD) is estimated to impact between 13% and 32% of the global population. NAFLD has been more clearly described as having 5% or more hepatic steatosis without hepatocellular damage. Hepatic steatosis or the buildup of extra adipose tissue in the liver is a condition inducing NAFLD. The disease development of NAFLD was also known as nonalcoholic steatohepatitis which characterized by inflammatory changes that can lead to progressive liver injury, cirrhosis, and hepatocellular carcinoma. Some species of brown algae were reported and proven to content phytocomplex with polysaccharides, phlorotannins and other polyphenols, and sulfolipids as discussed. The mechanisms of action underlying the preventative effects of brown algae on NAFLD have been the subject of very few investigations. However, the ideal conditions for determining the potential health benefits that these algae may have cannot be established. Moreover, the advantageous benefits of algae reported in rodents must also be proven in humans in future studies and investigations. The aim of this review is to provide scientific information on the therapeutic benefits of brown algae on fatty liver in preclinical and clinical studies, along with the mechanisms of action involved.
... For example, in mice with type 2 diabetes, fucoxanthin at the dose of 400 mg/kg body weight exhibited an anti-diabetic effect and improved the lipid profile [15]. Furthermore, in obese premenopausal women who were non-diabetic and had non-alcoholic fatty liver disease, administration of 7.2 mg/day of fucoxanthin as a supplement resulted in increased energy expenditure and significant weight loss after 16 weeks [16]. In addition, in a 4-week clinical trial on Japanese adults, administration of fucoxanthin capsules (3 mg/day) reduced body weight, body mass index, and abdominal fats [17]. ...
The food industry has increasingly added nutrients and other ingredients to products to enhance their health benefits. Fucoxanthin is recognized for its benefits in mitigating obesity, diabetes, hypertension, and inflammation. Therefore, addition of fucoxanthin into goat milk yogurt, its stability, and the physicochemical properties of yogurt during processing and storage was investigated. Yogurts with and without fucoxanthin were manufactured by mixing goat whole milk (82.85%, w/w), powdered goat milk (10.68%, w/w), and sugar (6.47%, w/w). Fucoxanthin (0.052 mg/g of yogurt mix) was added to the treatment. The mix was heated at 80 °C for 30 min, cooled, inoculated with a culture, and incubated at 43 °C for 5 h. Fucoxanthin in the yogurt mix and yogurt was quantified by an HPLC method. The recoveries of fucoxanthin from the mix before and after heating were 98.25% and 98.83%, respectively. However, less fucoxanthin (90.13%) was recovered from the freshly prepared yogurt than from the mix. Heating the yogurt mix did not affect the concentration of fucoxanthin but adding the inoculum to the mix reduced its concentration during fermentation. During the storage period, the concentration of fucoxanthin in yogurt remained the same. Fucoxanthin did not adversely affect the chemical composition and physicochemical properties of yogurt, but it influenced the color, decreasing lightness (81.47 ± 0.09), and increasing redness (7.67 ± 0.09) and yellowness (38.24 ± 0.09). Thus, goat milk yogurt can be an effective food matrix to deliver fucoxanthin to human diet.
... • Has antioxidant and anti-obesity properties [198,199] Astaxanthin ...
Carotenoids are isoprenoid compounds that play a role as pigments in photosynthetic and non-photosynthetic organisms. Carotenoids are essential in biological systems by acting as antioxidants. Thus, carotenoids have numerous applications in the environment, food, and medical sectors. Presently, most of the commercially available carotenoids are either extracted from different plants or produced synthetically using chemicals. The need to develop naturally derived pigments made it indispensable to discover alternate sources of carotenoids. Microbes have immense potential to produce carotenoids and thus, act as promising substitutes for chemically synthesized carotenoids. Microbial carotenoid production offers advantages, such as controlled cultivation and minimized production period. Moreover, the capability of microbes to utilize lignocellulosic waste as a substrate for the synthesis of carotenoids makes the overall process more sustainable. This review highlights the production of carotenoids from bacterial, fungal, and algal sources, followed by genetic modification of carotenogenic and non-carotenogenic species. Lastly, the review summarizes the extraction process and the applications of carotenoids in different fields.
... Fucoxanthin may be found at small concentrations in plasma and other tissues only after prolonged daily administration, i.e., at least a week [120]. Larger absorption of fucoxanthin may be obtained if administered along with edible oil or lipid [122,123], while it is only poorly adsorbed when ingested as a component of seaweed [124]. A further interesting aspect of use of fucoxanthin as a nutrient in the market is its lack of toxicity. ...
The search for novel sources of nutrients is among the basic goals for achievement of sustainable progress. In this context, microalgae are relevant organisms, being rich in high-value compounds and able to grow in open ponds or photobioreactors, thus enabling profitable exploitation of aquatic resources. Microalgae, a huge taxon containing photosynthetic microorganisms living in freshwater, as well as in brackish and marine waters, typically unicellular and eukaryotic, include green algae (Chlorophyceae), red algae (Rhodophyceae), brown algae (Phaeophyceae) and diatoms (Bacillariophyceae). In recent decades, diatoms have been considered the most sustainable sources of nutrients for humans with respect to other microalgae. This review focuses on studies exploring their bio-pharmacological activities when relevant for human disease prevention and/or treatment. In addition, we considered diatoms and their extracts (or purified compounds) when relevant for specific nutraceutical applications.
... Similarly, in humans, FX had a significant effect on weight loss. Indeed, the consumption of a mixture of 300 mg pomegranate seed oil and 300 mg brown seaweed extract containing 2.4 mg FX notably reduced obese women's body weight and body and liver fat contents, and liver function tests were improved after 16 days of treatment [104]. Meanwhile, the daily intake of 3 mg FX displayed a positive weight loss effect in patients with obesity [105]. ...
Owing to its unique structure and properties, fucoxanthin (FX), a carotenoid, has attracted significant attention. There have been numerous studies that demonstrate FX’s anti-inflammatory, antioxidant, antitumor, and anti-obesity properties against inflammation-related diseases. There is no consensus, however, regarding the molecular mechanisms underlying this phenomenon. In this review, we summarize the potential health benefits of FX in inflammatory-related diseases, from the perspective of animal and cellular experiments, to provide insights for future research on FX. Previous work in our lab has demonstrated that FX remarkably decreased LPS-induced inflammation and improved survival in septic mice. Further investigation of the activity of FX against a wide range of diseases will require new approaches to uncover its molecular mechanism. This review will provide an outline of the current state of knowledge regarding FX application in the clinical setting and suggest future directions to implement FX as a therapeutic ingredient in pharmaceutical sciences in order to develop it into a treatment strategy against inflammation-associated disorders.
... Marine activity products from marine organisms such as algae, fish, and crustaceans, are attracting a lot of attention as new medicines and functional supplements are decreasing the risk of disease. Many active marine products have been confirmed to be safe and effective in the treatment of obesity [17,29]. In this study, we researched how the PFK complex could reduce body weight, lipid disorder, and risk of arteriosclerosis in 6 weeks of treatment. ...
Phycobiliproteins, fucoxanthin, and krill oil are natural marine products with excellent activities. In the study, we prepared the complex of phycobiliproteins, fucoxanthin, and krill oil (PFK) and assessed the anti-obesity, lipid-lowering, and antioxidant activities in high-fat diet rats. The results showed that the rats significantly and safely reduced body weight gain and regulated serum biochemical parameters at 50 mg/kg phycobiliproteins, 10 mg/kg fucoxanthin, and 100 mg/kg krill oil. Furthermore, the molecular mechanism study suggested that the complex of PFK confined the enzyme activities of lipid synthesis and enhanced antioxidant activity to improve obesity indirectly. The conclusions demonstrated that the complex of PFK has potent anti-obesity and hypolipidemic effects which have potential use as a natural and healthy food and medicine for anti-obesity and lowering blood lipids in the future.
... Specifically, for high-value streams like nutraceuticals and bioactive peptide research, the higher cost to produce purer protein powder can be acceptable for the health market application. Seaweed powders enriched with polyphenols and phlorotannins (Paradis et al. 2011), fucoidan (Myers et al. 2011), and fucoxanthin (Abidov et al. 2010) has been reported to benefit human subjects metabolically. Antihypertensive peptides from Wakame (Undaria pinnatifida) and Nori (Porphyra yezoensis) are commercially available in Japan as beverage, jelly, and powder (Hayes and Tiwari 2015). ...
Previous work on Pacific dulse (Devaleraea mollis), a fast-growing protein-rich red algae, revealed that protein recovery can be significantly improved with cellulase pretreatment and sequential extraction approach. Since solubilized protein fractions need to be precipitated out of solution for enrichment and pellet recovery for downstream applications, this study aimed to evaluate the effects of precipitation strategies on macroalgal protein yield. Extracted protein fractions were precipitated using trichloroacetic acid (TCA) or pH-shift method (HCl/NaOH), and protein concentrations were assessed using three quantification methods, namely modified Lowry, Dumas, and total amino acid analysis (TAA). Specific to each Osborne fraction (albumin, globulin, glutelin and prolamin), the pH-shift precipitation approach was optimized in consideration to the amount of protein pellet recovered, protein retained in supernatant, and volume of acid required for pH adjustment. This work shows that the optimized pH-shift method has competitive yield compared to that of TCA precipitation. Ethanol wash post-pellet collection improved purity of the freeze-dried powders in both precipitation approaches but had more pronounced effects to TCA pellets. This then suggests that a single step precipitation using the optimized pH-shift method can be employed as a food-grade method in the recovery of extracted Pacific dulse proteins. Overall, this work provides a pioneering insight on the recovery of Pacific dulse protein using a pH-shift approach, and how three protein quantification methods were streamlined for protein recovery assessment. As a promising complementary food protein and potential bioactive peptide (BAP) source, this work offers an upscalable and ecologically sustainable recovery approach for seaweed protein from an abundant natural resource on the Pacific coast.
... Providing food with a high antioxidant capacity, thermogenic ingredients and a hypocaloric diet is fundamental to reduce fat mass. In a 16-week, doubleblind, randomized, placebo-controlled study that investigated the effects of Xanthigen ® , a product combining fucoxanthin with punicic acid from pomegranate seed oil, Xanthigen ® promoted weight loss, reduced body and liver fat content, and improved liver function tests in obese non-diabetic premenopausal women [45]. However, there is limited data of studies assessing the effects of PE supplementation on body composition in healthy volunteers, and most of the research has been carried out in animal models with results comparable to those obtained in our study. ...
Pomegranates are known to possess anti-hypertensive, anti-atherogenic and cardioprotective effects mainly due to their pleiotropic effects on various cellular pathways, especially those triggered by oxidative stress. The aim of this study was to investigate the effect of natural standardized pomegranate (PE) extract on cardiovascular risk factors in 24 healthy volunteers who participated in a randomized, single-blind placebo-controlled study. There were 12 subjects in the PE group and 12 in the placebo group. Variables were measured at baseline and after 14 and 28 days of supplementation are anthropometry, BP, pulse wave velocity, fat and lean body mass, salivary and urinary cortisol, and cortisone, total phenolics, antioxidant capacity and lipid peroxidation. Urinary total phenolics excretion and antioxidant capacity were significantly increased after 14 and 28 days of PE intake. At day 28, there were also statistically significant decreases in systolic and diastolic blood pressure (BP), pulse wave velocity, body fat and fat mass, as well as an increase in lean body mass. Significant changes in the placebo group were not found. Glucocorticoid levels showed a significant decrease in saliva cortisol at day 28 (morning) in the PE group, and cortisol/cortisone ratio was significantly decreased following 28 days of PE intake at morning, noon, and evening. Urine free cortisol was significantly reduced at day 14. These findings suggest that pomegranate extract intake may improve antioxidant and oxidative stress status and play a beneficial role in the attenuation of some cardiovascular risk factors. Future studies should concentrate on overweight and older people.
... In a study of 151 obese premenopausal women who were given supplements containing fucoxanthin from brown seaweed and pomegranate seed oil extracts at various doses for almost 16 weeks, the group receiving 300 mg pomegranate seed oil and 300 mg seaweed extract (2.4 mg fucoxanthin) had a statistically significant decrease in waist circumference, body weight and body fat, without any side effects. Moreover, the group that received more than 2.4mg fucoxanthin showed an increase in resting energy expenditure compared to the placebo [65]. ...
Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: β-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean.
... Xanthigen is an anti-obesity fucoxanthin-based product (https://nektium.com/branded-ingredient/xanthigen/, accessed on 8 June 2022), which has been proven to reduce the body and liver fat content, as well as enhance liver function in human trials [56,57]. On the other hand, FucoVital is the first fucoxanthin-based product that obtained approval from the United States Food and Drug Administration (NDI1048, 2017) (Algatechnologies Ltd., Kibbutz Ketura, Israel). ...
Fucoxanthin is one of the light-harvesting pigments in brown microalgae, which is increasingly gaining attention due to its numerous health-promoting properties. Currently, the production of microalgal fucoxanthin is not yet feasible from an economic perspective. However, the cultivation of microalgae at favourable conditions holds great potential to increase the viability of this fucoxanthin source. Hence, this study aimed to review the fucoxanthin production of microalgae under different conditions systematically. A literature search was performed using the Web of Science, Scopus and PubMed databases. A total of 188 articles were downloaded and 28 articles were selected for the current review by two independent authors. Microalgae appeared to be a more reliable fucoxanthin source compared to macroalgae. Overall, a consensus fucoxanthin production condition was obtained and proposed: light intensity ranging from 10 to 100 µmol/m2/s could achieve a higher fucoxanthin content. However, the optimal light condition in producing fucoxanthin is species-specific. The current review serves as an antecedent by offering insights into the fucoxanthin-producing microalgae response to different culture factors via a systematic analysis. With the current findings and recommendations, the feasibility of producing fucoxanthin commercially could be enhanced and possibly achieve practical and sustainable fucoxanthin production.
... Furthermore, amarouciaxanthin A showed the strongest e ect, followed by fucoxanthinol and FUC, on the di erentiation of murine pre-adipocytes and adipocytes ( Maeda et al., 2006 ). In a human trail study conducted to test the anti-obesity e ect of FUC, a combination of pomegranate seed oil (300 mg) and brown seaweed extract (300 mg) containing FUC (2.4 mg) supplemented for 16 days resulted in the signifi cant reduction of body weight and liver fat content in obese women (Abidov et al., 2010). Overall, the fi ndings of the literature suggested that FUC and its metabolites from marine seaweed are a potential tool for obesity management. ...
... We have reported that dietary fucoxanthin exhibits beneficial functions to health such as anti-obesity and anti-diabetic effects in animal models [1,2]. Human studies have also shown a reduction in white adipose tissue weight and HbA1c level related to blood glucose regulation by fucoxanthin [3,4]. Therefore, there is interest towards fucoxanthin, for its utilization as a nutraceutical ingredient in the food industry. ...
Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-Ay mice. After 4 weeks of feeding with the experimental diets, the serum fucoxanthinol concentrations of the mice fed 0.2% SO and 0.5% monocaprin were higher than those of the 0.2% SO-fed mice. Furthermore, fucoxanthinol accumulation in the liver and small intestine tended to increase in a combination diet of 0.2% SO and 0.125–0.5% monocaprin compared with a diet of 0.2% SO alone, although amarouciaxanthin A accumulation was not different among the 0.2% SO-fed groups. These results suggest that a combination of monocaprin with fucoxanthin-containing SO is an effective treatment for improving the bioavailability of fucoxanthin.
... The expressions of lipogenic enzymes ACC, FAS, and G6PDH and the transcriptional factor of SREBP-1c are significantly reduced while the expression of lipid-metabolizing enzymes CPT1 and CYP7A1 are significantly increased after Fx treatments [247]. Abidov also reported that Fx significantly reduces body weight, body and liver fat content and serum triglycerides (TG) [248]. Besides, Jeon reported that Fx exerts anti-obesity effects by reducing the activities of the enzymes involved in fatty acid (FA) synthesis, FA oxidation and TG synthesis in both liver and epididymal adipose tissue. ...
Breast cancer (BC) is one of the most common cancers diagnosed and the leading cause of cancer-related death in women. Although there are first-line treatments for BC, drug resistances and adverse events have been reported. Given the incidence of BC keeps increasing, seeking novel therapeutics is urgently needed. Fucoxanthin (Fx) is a dietary carotenoid commonly found in seaweeds and diatoms. Both in vitro and in vivo studies show that Fx and its deacetylated metabolite fucoxanthinol (Fxol) inhibit and prevent BC growth. The NF-κB signaling pathway is considered the major pathway contributing to the anti-proliferation, anti-angiogenesis and pro-apoptotic effects of Fx and Fxol. Other signaling molecules such as MAPK, MMP2/9, CYP and ROS are also involved in the anti-cancer effects by regulating the tumor microenvironment, cancer metastasis, carcinogen metabolism and oxidation. Besides, Fx also possesses anti-obesity effects by regulating UCP1 levels and lipid metabolism, which may help to reduce BC risk. More importantly, mounting evidence demonstrates that Fx overcomes drug resistance. This review aims to give an updated summary of the anti-cancer effects of Fx and summarize the underlying mechanisms of action, which will provide novel strategies for the development of Fx as an anti-cancer therapeutic agent.
Background
Fucoxanthin has been widely investigated owing to its beneficial biological properties, and the model diatom Phaeodactylum tricornutum , possessing fucoxanthin (Fux) chlorophyll proteins as light-harvesting systems, is considered to have the potential to become a commercial cell factory for the pigment production.
Results
Here, we compared the pigment contents in 10 different P. tricornutum strains from the globe, and found that strain CCMP631 (Pt6) exhibited the highest Fux content but with a low biomass. Comparison of mRNA levels revealed that higher Fux content in Pt6 was related with the higher expression of gene violaxanthin de-epoxidase-like (VDL) protein 1 ( VDL1 ), which encodes the enzyme catalyzing the tautomerization of violaxanthin to neoxanthin in Fux biosynthesis pathway. Single nucleotide variants of VDL1 gene and allele-specific expression in strains Pt1 (the whole genome sequenced strain CCMP632) and Pt6 were analyzed, and overexpressing of each of the 4 VDL1 alleles, two from Pt1 and two from Pt6, in strain Pt1 leads to an increase in downstream product diadinoxanthin and channels the pigments towards Fux biosynthesis. All the 8 VDL1 overexpression (OE) lines showed significant increases by 8.2 to 41.7% in Fux content without compromising growth, and VDL1 Allele 2 OE lines even exhibited the higher cell density on day 8, with an increase by 24.2–28.7% in two Pt1VDL1-allele 2 OE lines and 7.1–11.1% in two Pt6VDL1-allele 2 OE lines, respectively.
Conclusions
The results reveal VDL1, localized in the plastid stroma, plays a key role in Fux over-accumulation in P. tricornutum . Overexpressing VDL1 , especially allele 2 , improved both the Fux content and growth rate, which provides a new strategy for the manipulation of Fux production in the future.
Background: Microalgae like Phaeodactylum tricornutum (PT) contain the carotenoid, fucoxanthin, which has been purported to promote fat loss, lower blood lipids, and improve glucose management. This study examined whether dietary supplementation with microalgae extracts from PT containing 4.4 mg/d of fucoxanthin affects changes in body composition or health markers in overweight women during an exercise and diet intervention. Materials and Methods: A total of 37 females (28.6 ± 7.9 years, 80.2 ± 14.9 kg, 29.6 ± 3.8 kg/m², 41.4 ± 4.2% fat) fasted for 12 h, donated a fasting blood sample, completed health and mood state inventories, and undertook body composition, health, and exercise assessments. In a counterbalanced, randomized, and double-blind manner, participants ingested a placebo (PL), or microalgae extract of Phaeodactylum tricornutum standardized to 4.4 mg of fucoxanthin (FX) for 12 weeks while participating in a supervised exercise program that included resistance-training and walking (3 days/week) with encouragement to accumulate 10,000 steps/day on remaining days of the week. The diet intervention involved reducing energy intake by about −300 kcal/d (i.e., ≈1400–1600 kcals/d, 55% carbohydrate, 30% fat, 15% protein) to promote a −500 kcal/d energy deficit with exercise. Follow-up testing was performed at 6 and 12 weeks. A general linear model (GLM) with repeated measures statistical analysis was used to analyze group responses and changes from baseline with 95% confidence intervals. Results: Dietary supplementation with microalgae extract from PT containing fucoxanthin for 12 weeks did not promote additional weight loss or fat loss in overweight but otherwise healthy females initiating an exercise and diet intervention designed to promote modest weight loss. However, fucoxanthin supplementation preserved bone mass, increased bone density, and saw greater improvements in walking steps/day, resting heart rate, aerobic capacity, blood lipid profiles, adherence to diet goals, functional activity tolerance, and measures of quality of life. Consequently, there appears to be some benefit to supplementing microalgae extract from PT containing fucoxanthin during a diet and exercise program. Registered clinical trial #NCT04761406.
Punica granatum L., commonly known as pomegranate, is a typical fruit of Asia, Mediterranean countries, the Middle East and the USA. While in ancient times pomegranate was considered an ornamental plant, nowadays numerous scientific studies have highlighted its antioxidant and anti-radical activities, making it a “superfood”. Pomegranate presents a high content of natural bioactive compounds (NBCs), and its consumption appears to exert numerous healthy effects, in particular, in several pathological conditions as metabolic syndrome, cancer, nephrolithiasis, urinary tract infections and neurodegenerative diseases. Moreover, recent studies have pointed out the possible beneficial action of pomegranate on oral health. For these reasons, the utility of pomegranate in internal medicine and dentistry represents a promising field, as it could enable the development of innovative natural adjuvant therapies and empower standard pharmaceutical therapies.
Background: Myocardial ischemia and reperfusion injury (MIRI) is an severe complication during revascularization therapy in patients with myocardial infarction. It is urgent to find more therapeutic target to MIRI. Recently,...
The color difference in human subcutaneous fat (SF) and orbital fat (OF) is apparent, but the reasons have been rarely elaborated. We speculate that differences in carotenoid and lipid contents may account for the discrepancy in color. In this study, the intrinsic differences in SF and OF were analyzed using ultrahigh-performance liquid chromatography coupled with Q-Exactive liquid chromatography mass spectrometry/mass spectrometry (UPLC-QE Plus LC-MS/MS). Lipid profiling was performed in an independent batch. The morphology between orbital septum and SF differed statistically in the size of adipocytes and the distribution area of adipocytes. We compared carotenoid contents between two groups (seven samples) and found that lutein was more abundant in SF than that in OF with a p-value of 0.0409, suggesting that lutein could be mainly responsible for the yellow color of adipose tissue. Lipidomic results proved that SF and OF were well differentiated. Totally, 402 lipid features were detected, with 349 features in the positive ion mode and 53 features in the negative ion mode. Features (99.9%) in the positive ion mode and features (98.7%) in the negative ion mode well described various separation patterns in principal component analysis. Thirty-two features selected by variable importance in projection might account for the diversity of compounds in SF and OF. In conclusion, SF and OF differed from each other in carotenoids and lipidome. It is helpful to study the metabolism process of lipid droplets in adipocytes.
Millions of dollars have been spent on nutritional and herbal supplements, which are used by many overweight people to lose weight. However, there are concerns about the effectiveness and safety of several supplements. By boosting energy expenditure, satiety, fat oxidation, inhibiting dietary fat absorption, moderating carbohydrate metabolism, raising fat excretion, increasing water elimination, and improving mood, supplements are thought to aid in weight reduction. This study provides an overview of the present status of the research on a few particular dietary supplements, herbal combinations, and combination products, as this field is evolving quickly. More studies on numerous supplements are required to verify their efficacy because they have not been examined in randomised controlled trials. Nutritionists and medical experts should go through dietary supplement use with patients and notify the FDA of any negative side effects. Additional rules would be required for the manufacture, sale, and marketing of these supplements.
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease. Fucoxanthin, a red-orange marine carotenoid, is found in natural marine seaweeds with high antioxidant activity and several other remarkable biological features. The aim of this review is to gather evidence of the positive benefits of fucoxanthin on NAFLD. Fucoxanthin provides an extensive list of physiological and biological properties, such as hepatoprotective, anti-obesity, anti-tumor, and anti-diabetes properties, in addition to antioxidant and anti-inflammatory properties. This review focuses on published research on the preventative effects of fucoxanthin on NAFLD from the perspective of human clinical trials, animal experiments in vivo, and in vitro cell investigations. Using a variety of experimental designs, including treatment dosage, experiment model, and experimental periods, the positive effects of fucoxanthin were demonstrated. Fucoxanthin’s biological activities were outlined, with an emphasis on its therapeutic efficacy in NAFLD. Fucoxanthin showed beneficial effects in modulating lipid metabolism, lipogenesis, fatty acid oxidation, adipogenesis, and oxidative stress on NAFLD. A deeper comprehension of NAFLD pathogenesis is essential for the development of novel and effective therapeutic strategies.
Hypertension, type-2-diabetes (T2D) and obesity are contributory risk factors for the development of metabolic syndrome. Peptides, polyphenols and polysaccharides may inhibit enzymes involved in the disease pathways of this disorder. Peptide hydrolysates (PEP), polyphenol (PP) and polysaccharide (PS) extracts generated from the Australian seaweeds Phyllospora comosa (Labillardière) C. Agardh, Ecklonia radiata (C. Agardh) J. Agardh, and Ulva ohnoi M. Hiraoka & S. Shimada were screened in vitro for their potential to inhibit enzymes important in the control of diseases associated with metabolic syndrome. These enzymes include angiotensin-I-converting enzyme (ACE-1; EC 3.4.15.1) which affects the development of hypertension in mammals, α-amylase (EC 3.2.1.1) and lipase (EC 3.1.1.3) which play a role in the development of T2D and dietary lipid absorption, respectively. The inhibitory activity of each seaweed extract was determined using established in vitro colorimetric methods with mammalian-derived enzymes and their respective substrates. The ACE-1 half-maximal inhibitory (IC50) concentrations of generated bioactive extracts ranged from 167.52 ± 3.17 µg mL⁻¹ (U. ohnoi PEP) to 713.84 ± 12.45 µg mL⁻¹ (E. radiata PS). None of the extracts screened displayed IC50 values comparable to the positive control drug Captopril (8.87 ± 0.04 µg mL⁻¹). IC50 values determined for extracts that inhibited α-amylase ranged from 58.31 ± 1.41 µg mL⁻¹ (P. comosa PP) to 515.24 ± 10.53 µg mL⁻¹ (E. radiata PEP). All PS and PP had significantly lower IC50 values than the α-amylase inhibitor control, Acarbose (89.90 ± 0.15 µg mL⁻¹). Lipase IC50 values determined for extracts ranged from 52.14 ± 2.77 µg mL⁻¹ (P. comosa PP) to 876.30 ± 34.92 µg mL⁻¹ (E. radiata PEP). All PP had significantly lower IC50 values than the lipase inhibitory drug Orlistat (70.83 ± 0.07 µg mL⁻¹). To the authors’ knowledge there are no published values for the inhibitory potential of P. comosa, E. radiata or U. ohnoi extracts against the enzymes ACE-1, α-amylase, or lipase. These findings demonstrate the functional food potential of P. comosa, E. radiata and U. ohnoi polyphenols, polysaccharides and peptides.
Diabetes is prevailing in pandemic proportions, as nearly half a billion population is affected by diabetes worldwide. The expenditure on diabetes healthcare is estimated to grow to $845 billion by 2045. However, identifying an efficient drug for completely curing diabetes and its complications is still unattainable. Given these challenges, we have discussed the range of storage molecules and pigments derived from microalgae, macroalgae, and cyanobacteria and explored their promising potential as antidiabetic drugs. Further, in silico studies have also been investigated for elucidating plausible molecular mechanisms of the most promising algal compounds. It is noteworthy that the chemical synthesis of bulky compounds is a cumbersome and less efficient process, whereas naturally occurring bulky compounds have complex stereospecific ornamentation of chemical groups executed by the number of stereospecific enzymes. On the other hand, growing algae in controlled conditions is an easy method to get various algal metabolites with a diverse array of chemical structures exhibiting pleiotropic antidiabetic activities. This review highlights the promising potential of algal metabolites to treat diabetes by targeting a variety of molecular mechanisms involved in the pathogenesis of diabetes.
Background: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer with an extremely dismal prognosis and few treatment options. As a desmoplastic tumor, tumor cells are girdled by stroma composed of tumor-associated fibroblasts (CAFs) and their secreted stromal components. The rapidly proliferating tumor cells, together with the tumor stroma, exert additional solid tissue pressure on tumor vasculature and surrounding tissues, severely obstructing therapeutic agent from deep intratumoral penetration, and resulting in tumor metastasis and treatment resistance. Fucoxanthin (FX), a xanthophyll carotenoid abundant in marine algae, has attracted widespread attention as a promising alternative candidate for tumor prevention and treatment. Twist is a pivotal regulator of epithelial to mesenchymal transition (EMT), and its depletion has proven to sensitize antitumor drugs, inhibit metastasis, reduce CAFs activation and the following interstitial deposition, increase tumor perfusion, and allow more drugs to be delivered across the tumor stroma.
Results: Herein, our studies proposed a novel self-assembled polymer nanoparticle (siTwist/FX@HES-CH NPs) based on the amino-modified hydroxyethyl starch (HES-NH2) grafted with hydrophobic segment cholesterol (CH). Systematic studies demonstrated that the co-delivery strategy of natural product FX and nucleic acid drug Twist siRNA (siTwist) could not only synergistically kill tumor cells, but also inhibit the CAFs activation and extracellular matrix synthesis. Loose tumor stroma further facilitated transvascular transport and deep penetration of nanoparticles, obviously alleviating the primary tumor burden and inhibiting lung metastasis.
Conclusions: This dually functional nanomedicine that targets both tumor cells and tumor microenvironment (TME) could form a potent anti-TNBC therapeutic cyclical feedback loop, providing a new paradigm for TNBC treatment.
Brown and beige adipocytes are equipped with abundant mitochondrial uncoupling protein 1 (UCP1) to dissipate energy in the form of heat. Activation of brown adipocytes or inducing white adipocyte browning in rodents and humans is associated with significant inprovements in glucose and lipid metabolism. Therefore, stimulating brown or beige adipogenesis offers an attractive therapeutic strategy in combating the growing epidemic of obesity and related diseases. In addition to cold exposure, a well-defined stimuli for brown adipocytes tissue thermogenesis, some food-derived components serve as an environmental inducer for UCP1-mediated thermogenesis. This chapter will be focused on the role of UCP1 in regulating energy homeostasis and how fucoxanthin, a carotenoid in edible seaweeds, promotes the expression and activity of UCP1 to combat obesity.
Brown algae have been considered a potential source of bioactives and used as a dietary supplement to manage obesity and its associated health complications. However, its effective use is limited due to heavy metals and microbial contamination, unawareness of health benefits and limited dietary exploitation. We developed, the Indian brown algae Padina tetrastromatica and barley-based anti-obesity food (AOF) and examined for microbial and heavy metal safety. Additionally, acute [0 (control), 50, 100, 200, 500 g AOF/kg diet] and sub-acute [0, 5, 50 g AOF/kg diet] doses of AOF were fed to C57BL6 mice and toxicity was examined. The physical, locomotory, hematological, biochemical parameters and histopathology were examined. Postprandial plasma and tissue levels of fucoxanthin and its metabolites were analyzed. Feeding AOF did not affect the general behavior, food and water intake, growth or survival of animals. Biochemical indices did not show any differences between AOF-fed and control groups. However, significantly lower levels of plasma cholesterol and triglycerides in groups fed 5 and 50 g of AOF/kg diet were observed. The post-mortem examination revealed no macroscopic/microscopic alteration in the vital organs. Overall, results validate that AOF is a safe and effective dietary supplement (even at higher doses of 500 g AOF/kg) to mitigate obesity.
Graphical abstract:
Supplementary information:
The online version contains supplementary material available at 10.1007/s13197-022-05483-4.
Algae have received substantial consideration as a potential feedstock for extensive applications in the environmental sector, biofuel production, and biomedical engineering. Rapid climate changes, shrinking natural resources, and food crises are on the rise globally. The release of untreated industrial wastewaters containing vast amounts of carbon, nitrogen (N), and phosphorus (P) causes severe pollution and environmental damage. Hence, the recovery of such nutrients is required through a suitable sustainable process. Microalgae-based technologies have gained significant attention compared to other techniques due to their sustainable and cost-effective treatment strategies for removing wastewater nutrients. Algal biomass could potentially be used for bioenergy production and high-value bioproducts. High operational costs and low yield are the main limitations for developing microalgae-based biorefineries. Therefore, most researchers focus on an integrated approach for the cultivation of a suitable algal strain and its downstream processing. Algal biomass production for use as a biofuel is not feasible from a techno-economic perspective. A biorefinery concept could be a more suitable approach for bio-oil extraction, and the remaining biomass could be used for several biomedical applications. This chapter offers an overview of algae and their use in bioremediation, bioenergy production, and biomedical applications. Recent challenges and prospects in the algae-based sector, which has become quite promising at present, have also been discussed.
Dual-photon absorptiometry (DPA) allows separation of body mass into bone mineral, fat, and fat-free soft tissue. This report evaluates the potential of DPA to isolate appendages of human subjects and to quantify extremity skeletal muscle mass (limb fat-free soft tissue). The method was evaluated in 34 healthy adults who underwent DPA study, anthropometry of the limbs, and estimation of whole-body skeletal muscle by models based on total body potassium (TBK) and nitrogen (TBN) and on fat-free body mass (FFM). DPA appendicular skeletal muscle (22.0 +/- 3.1 kg, mean +/- SD) represented 38.7% of FFM, with similar proportions in males and females. There were strong correlations (all p less than 0.001) between limb muscle mass estimated by DPA and anthropometric limb muscle areas (r = 0.82-0.92), TBK (r = 0.94), and total-body muscle mass based on TBK-FFM (r = 0.82) and TBK-TBN (r = 0.82) models. Appendicular skeletal muscle mass estimated by DPA is thus a potentially practical and accurate method of quantifying human skeletal muscle mass in vivo.
We developed a reproducible ELISA for C-reactive protein (CRP), calibrated with WHO Reference Material, for which intra- and interassay CVs were 3.0% and 6.0%, respectively. Analytical recovery was 97.9%. The distribution of CRP in a healthy blood donor population (n = 143) was nongaussian, with 2.5th, 50th, and 97.5th percentile values of 0.08, 0.64, and 3.11 mg/L, respectively. There was no sex-related difference, and the association with age was weak. In a study of variability [by the method of Fraser and Harris (Crit Rev Clin Lab Sci 1989;27:409-37)], the analytical variability was 5.2%; the within-subject variability, CVI, was 42.2%; and the between-subject variability, CVG, was 92.5%. The critical difference for sequential values significant at P < or =0.05 (i.e., the smallest percentage change unlikely to be due to analytical variability or CVI) was calculated as 118%, and the index of individuality, CVI/CVG, was 0.46. This suggests that CRP, like many clinical chemistry analytes, has limited usefulness in detecting early disease-associated changes when used in conjunction with a healthy reference interval. From a molecular epidemiological standpoint, the usefulness of CRP in longitudinal studies is suggested by the small index of individuality and by observations that (a) short-term fluctuations were infrequent, (b) all data stayed within the reference interval, and (c) relative rankings of the subjects over 6 months only moderately deteriorated.
The activities of hepatic enzymes involved in fatty acid synthesis and oxidation were compared in rats fed diets containing different proportions of dried powder of the brown seaweed, Undaria pinnatifida (wakame). Rats were fed diets containing 0, 0.5, 1.0, 2. 0, 5.0 and 10 g/100 g of dried wakame powder. Experimental diets were adjusted to provide consistent amounts of most nutrients, but mineral concentrations were not standardized. After the 21-d feeding period, serum and liver triacylglycerol levels in rats fed diets in which wakame constituted at least 2% were significantly lower than those in rats fed the control diet. The activity of glucose-6-phosphate dehydrogenase was significantly lower in rats fed the 5 and 10% wakame diets than in rats fed the control diet. In contrast, 10% wakame diet increased activities of enzymes involved in the beta-oxidation pathway including hepatic carnitine palmitoyltransferase, acyl-CoA dehydrogenase, acyl-CoA oxidase, enoyl-CoA hydratase and 2,4-dienoyl-CoA reductase. Some differences were detected in rats fed 5% wakame as well. These results suggest that alterations of the activities of enzymes involved in fatty acid metabolism in the liver are responsible for the serum triacylglycerol-lowering effect of dietary wakame. Thus, wakame may be useful as a food to prevent hyperlipidemia.
Use non-pharmacological measures in all hypertensive and borderline hypertensive people. Initiate antihypertensive drug therapy in people with sustained systolic blood pressures (BP) >/=160 mm Hg or sustained diastolic BP >/=100 mm Hg. Decide on treatment in people with sustained systolic BP between 140 and 159 mm Hg or sustained diastolic BP between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease or a 10-year coronary heart disease (CHD) risk of >/=15% according to the Joint British Societies CHD risk assessment programme/risk chart. In people with diabetes mellitus, initiate antihypertensive drug therapy if systolic BP is sustained >/=140 mm Hg or diastolic BP is sustained >/=90 mm Hg. In non-diabetic hypertensive people, optimal BP treatment targets are: systolic BP <140 mm Hg and diastolic BP <85 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some hypertensive people. In diabetic hypertensive people, optimal BP targets are; systolic BP <140 mm Hg and diastolic BP <80 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <140/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some people with diabetes and hypertension. In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or beta-blockers are preferred as first-line therapy for the majority of hypertensive people. In the absence of compelling indications for beta-blockade, diuretics or long acting dihydropyridine calcium antagonists are preferred to beta-blockers in older subjects. Compelling indications and contraindications for all antihypertensive drug classes are specified. For most hypertensives, a combination of antihypertensive drugs will be required to achieve the recommended targets for blood pressure control. Other drugs that reduce cardiovascular risk must also be considered. These include aspirin for secondary prevention of cardiovascular disease, and primary prevention in treated hypertensive subjects over the age of 50 years who have a 10-year CHD risk >/=15% and in whom blood pressure is controlled to the audit standard. In accordance with existing British recommendations, statin therapy is recommended for hypertensive people with a total cholesterol >/=5 mmol/L and established vascular disease, or 10-year CHD risk >/=30% estimated from the Joint British Societies CHD risk chart. Glycaemic control should also be optimised in diabetic subjects. Specific advice is given on the management of hypertension in specific patient groups, ie, the elderly, ethnic subgroups, diabetes mellitus, chronic renal disease and in women (pregnancy, oral contraceptive use and hormone replacement therapy). Suggestions for the implementation and audit of these guidelines in primary care are provided.
Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU. m(-2). min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2). Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis. In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied. Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI. Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients. Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs. -84% in control subjects; P = 0.003). Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal. In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs. 84% in control subjects (P = 0.002). Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP. There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status. Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis. We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity. NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance.
Nonalcoholic fatty liver disease (NAFLD) is common in patients with the metabolic syndrome, and it is expected to become more common in countries where obesity, one of the components of the metabolic syndrome, is increasing.
Conjugated fatty acid, the general term of positional and geometric isomers of polyunsaturated fatty acids with conjugated double bonds, has attracted considerable attention because of its potentially beneficial biological effects. In the present study, dietary effect of pomegranate seed oil rich in punicic acid (9cis, 11trans, 13cis-conjugated linolenic acid; 9c, 11t, 13c-CLNA) on lipid metabolism was investigated in obese, hyperlipidemic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. After 2 weeks feeding period, OLETF rats revealed obesity and hyperlipidemia compared with their progenitor LETO rats. Feeding of the diet supplemented with 9% safflower oil and 1% pomegranate seed oil (9c, 11t, 13c-CLNA diet) did not affect abdominal white adipose tissue weights and serum lipid levels compared with the diet supplemented with 10% safflower oil (control diet) in OLETF rats. However, the accumulated hepatic triacylglycerol was markedly decreased by 9c, 11t, 13c-CLNA diet in OLETF rats. Activities of hepatic enzymes related to fatty acid synthesis and fatty acid beta-oxidation were not altered by 9c, 11t, 13c-CLNA diet. Levels of monounsaturated fatty acid (MUFA), major storage form of fatty acid, in serum triacylglycerol were markedly higher in obese, hyperlipidemic OLETF rats than in lean LETO rats. In addition, 9c, 11t, 13c-CLNA diet significantly decreased MUFA levels in OLETF rats. This is the first study showing that 9c, 11t, 13c-CLNA suppresses delta-9 desaturation in vivo, and we suggest that the alleviation of hepatic triacylglycerol accumulation by 9c, 11t, 13c-CLNA diet was, at least in part, attributable to the suppression of delta-9 desaturation in OLETF rats.
Persons with high intake of polyunsaturated fatty acids (PUFAs) have lower cardiovascular morbidity and mortality. The protective effect of PUFAs is mediated by multiple mechanisms, including their antiinflammatory properties. The association of physiological PUFA levels with pro- and antiinflammatory markers has not been established.
In 1123 persons (aged 20-98 yr), we examined the relationship between relative concentration of fatty acids in fasting plasma and level of inflammatory markers. Adjusting for age, sex, and major confounders, lower arachidonic and docosahexaenoic acids were associated with significantly higher IL-6 and IL-1ra and significantly lower TGFbeta. Lower alpha-linolenic acid was associated with higher C-reactive protein and IL-1ra, and lower eicosapentaenoic acid was associated with higher IL-6 and lower TGFbeta. Lower docosahexaenoic acid was strongly associated with lower IL-10. Total n-3 fatty acids were associated with lower IL-6 (P = 0.005), IL-1ra (P = 0.004), and TNFalpha (P = 0.040) and higher soluble IL-6r (P < 0.001), IL-10 (P = 0.024), and TGFbeta (P = 0.0012). Lower n-6 fatty acid levels were significantly associated with higher IL-1ra (P = 0.026) and lower TGFbeta (P = 0.014). The n-6 to n-3 ratio was a strong, negative correlate of IL-10. Findings were similar in participants free of cardiovascular diseases and after excluding lipids from covariates.
In this community-based sample, PUFAs, and especially total n-3 fatty acids, were independently associated with lower levels of proinflammatory markers (IL-6, IL-1ra, TNFalpha, C-reactive protein) and higher levels of antiinflammatory markers (soluble IL-6r, IL-10, TGFbeta) independent of confounders. Our findings support the notion that n-3 fatty acids may be beneficial in patients affected by diseases characterized by active inflammation.
Fucoxanthin is a major carotenoid found in edible seaweed such as Undaria pinnatifida and Hijikia fusiformis. We investigated the suppressive effects of fucoxanthin and its metabolite, fucoxanthinol, on the differentiation of 3T3-L1 preadipocytes to adipocytes. Fucoxanthin inhibited intercellular lipid accumulation during adipocyte differentiation of 3T3-L1 cells. Furthermore, fucoxanthin was converted to fucoxanthinol in 3T3-L1 cells. Fucoxanthinol also exhibited suppressive effects on lipid accumulation and decreased glycerol-3-phosphate dehydrogenase activity, an indicator of adipocyte differentiation. The suppressive effect of fucoxanthinol was stronger than that of fucoxanthin. In addition, in 3T3-L1 cells treated with fucoxanthin and fucoxanthinol, peroxisome proliferator-activated receptor gamma (PPARgamma), which regulates adipogenic gene expression, was down-regulated in a dose-dependent manner. These results suggest that fucoxanthin and fucoxanthinol inhibit the adipocyte differentiation of 3T3-L1 cells through down-regulation of PPARgamma. Fucoxanthinol had stronger suppressive effects than fucoxanthin on adipocyte differentiation in 3T3-L1 cells.
The aim of this review is to update concepts of the nonalcoholic fatty liver disease (NAFLD) and to establish a relationship between this condition and obesity.
By means of a comprehensive literature review where special attention was devoted to articles published in the last 5 years, NAFLD is discussed in view of new concepts, diagnosis, staging, and treatment.
NAFLD is emerging as one of the main causes of chronic liver disease and it is believed to be the hepatic component of the metabolic syndrome, whose central features include obesity, hyperinsulinemia, peripheral insulin resistance, diabetes, dyslipidemia, and hypertension. The surgical treatment of morbid obesity is one of the options available for the treatment of NAFLD.
Nonalcoholic fatty liver disease is strongly related with obesity.
Moderate hypertriglyceridemia is fairly common, and elevated triglycerides are a risk factor for coronary heart disease. The omega-3 fatty acids EPA and DHA have been shown to lower triglycerides in many clinical studies. Prescription omega-3 fatty acid concentrates (P-OM3) are indicated for use in people with very high triglycerides (> 500 mg/dl). Current guidelines recommend that triglycerides should be less < 150 mg/dl.
This review provides an overview of the use of omega-3 concentrates (both P-OM3 and over-the-counter fish oil) to lower triglycerides in people who have moderate hypertriglyceridemia (triglycerides in the range of 150 - 500 mg/dl). The objectives were to examine clinical evidence, describe the magnitude of effects and predict future clinical use of P-OM3.
Published, peer-reviewed studies of omega-3 concentrates were included if they were placebo-controlled, double-blind, of sufficient size to demonstrate triglyceride lowering, and studied a population described as having a mean baseline triglyceride value of 150 - 500 mg/dl. Studies using the 4-g dose of P-OM3 were used to develop a model of percent triglyceride lowering as a function of baseline levels.
P-OM3 are effective in reducing triglycerides by approximately 30% in this population and are likely to be combined with other drugs (e.g., statins) to treat combined dyslipidemia.
Summary A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.
Reactions between a carotenoid, fucoxanthin and 1,1-diphenyl-2-picrylhydrazyl were investigated both under anoxic and aerobic conditions. Fucoxanthin equimolarly reacted with 1,1-diphenyl-2-picrylhydrazyl under anoxic conditions. Under aerobic conditions, only a part of fucoxanthin consumed 1,1-diphenyl-2-picrylhydrazyl and the degree of reaction fluctuated with repeated trials. β-Carotene or other carotenoids, β-cryptoxanthin, zeaxanthin, licopen and lutein, were also examined in the reaction with 1,1-diphenyl-2-picrylhydrazyl under anoxic conditions. All these compounds scarcely reacted with 1,1-diphenyl-2-picrylhydrazyl.
In order to elucidate the long-term alterations in cholesterol transport and esterification as a part of the changes in the carbohydrate and lipoprotein metabolism subsequent to calorific restriction, 15 obese women were investigated before and after treatment with vertical banded gastroplasty. Insulin resistance and production, lipid levels in plasma, lipoproteins and the lecithin: cholesterol acyl transferase (LCAT) rate were assessed. There was a 60% decrease in mean calorific intake six months after surgery. A slight hyperglycaemia was almost normalized concomitant with a reduction of serum insulin and C-peptide after 1 year. The very low density lipoprotein (VLDL) level was unchanged. The high density lipoprotein (HDL) levels tended to rise after 1 year, when there was a significant increase of the HDL-2 subfraction. The lipid levels in the lipoprotein fractions showed a rise in mean HDL-2 cholesterol. Both the molar and fractional rates of LCAT were decreased. These results suggest that long-term calorific restriction reduces insulin resistance and production, and lowers VLDL levels and VLDL and cholesterol synthesis. However, the low density lipoprotein cholesterol levels are unchanged, probably because of a decrease in the previously elevated fractional cholesterol removal.
The purpose of the present study was to test the validity of the electrical impedance method for estimation of total body water and lean body mass in adult Danes with large differences of obesity and fat distribution, and to develop algorithms for estimation of body water, lean body mass and fat from measurement of impedance. The results of the electrical impedance method were compared in 139 Danes aged 35-65 years, to those of a four-compartment-model based on measurements of both total body potassium (whole body counting) and total body water (dilutometry). The comparison confirmed the validity of the impedance method. Equations for predicting body water and lean body mass in Danes are given. A significant difference was found between two instruments of the same model. In spite of the fact that the test resistance supplied by the manufacturer gave identical measurements, measurements on humans diverged on average by 31 ohm. A cross-validation study showed that most of the algorithms found in the literature for predicting lean body mass from impedance yield reliable results.
Partly desialylated transferrin was measured in the serum of subjects with chronic alcoholism, of patients with non-alcoholic-related steatohepatitis, diabetes, and other non-alcoholic liver diseases, and of healthy controls. In non-alcoholic patients and controls the maximum desialylated transferrin expressed in relation to total transferrin was 1.5%. This value was exceeded in 18 (90%) of the 20 alcoholics. By contrast, gamma-glutamyl transferase was within the reference range in 9 of the alcoholics.
A 54-year-old woman with obesity, type II diabetes mellitus, hyperlipidemia, and massive hepatomegaly was found to have severe steatosis and cirrhosis on liver biopsy. Complete evaluation led to the diagnosis of fatty cirrhosis associated with obesity and diabetic mellitus. She underwent four months of fasting with a protein-carbohydrate and vitamin-mineral liquid supplement to control her weight and metabolic abnormalities and to evaluate the effect of this diet on her liver disease. She lost 40 pounds to ideal body weight, normalized her serum glucose and lipids, and decreased total liver height by one third. Liver biopsy at the completion of her diet showed inactive cirrhosis and complete resolution of steatosis. Supplemented fasting with only modest weight loss can safely resolve fatty liver in obese diabetics with nonalcoholic steatosis and cirrhosis. Aggressive dietary approaches to achieve long-term weight loss deserve study in this subgroup of diabetics with unexplained chronic liver disease.
Nonalcoholic steatohepatitis is a poorly understood and hitherto unnamed liver disease that histologically mimics alcoholic hepatitis and that also may progress to cirrhosis. Described here are findings in 20 patients with nonalcoholic steatohepatitis of unknown cause. The biopsy specimens were characterized by the presence of striking fatty changes with evidence of lobular hepatitis, focal necroses with mixed inflammatory infiltrates, and, in most instances, Mallory bodies; Evidence of fibrosis was found in most specimens, and cirrhosis was diagnosed in biopsy tissue from three patients. The disease was more common in women. Most patients were moderately obese, and many had obesity-associated diseases, such as diabetes mellitus and cholelithiasis. Presence of hepatomegaly and mild abnormalities of liver function were common clinical findings. Currently, we know of no effective therapy.
To identify prognostic metabolic and hormonal markers for long-term weight loss outcome in obese women.
Dietary intervention consisting of 36 weeks treatment by a 4.2 MJ/d low-fat high carbohydrate diet, and follow-up 2 1/2 years after termination of treatment.
Outpatient clinic in Copenhagen.
Forty consecutive female obese patients aged 15 to 62 years.
Weight loss.
The maximum weight loss (mean 16.2 kg, 95% CI 14.2-18.2) was positively associated to pre-treatment 24-h energy expenditure (P < 0.01), fat oxidation (%) (P < 0.02), plasma dihydrotestosterone (DHT) (P < 0.01), and to postprandial noradrenaline concentration (P < 0.04). Together these factors could explain 41% of the variation in maximum weight loss. Only 24-h EE and DHT had predictive power on weight loss after 36 weeks. Weight losses in upper and lower tertiles of DHT concentrations were 17.7 kg (14.1-21.4) and 9.8 kg (6.2-13.3) (P < 0.02). The adjusted relative risk of losing < 10 kg in the upper compared to the lower DHT tertile was 12% (4-32%). At 2 1/2 y follow-up 21 patients had maintained some of the weight loss (54%), while 14 patients had maintained > 5 kg weight loss (36%). High levels of pre-treatment DHT were also associated with better weight loss at 2 1/2 y follow-up.
The study suggests that in particular DHT, but also 24-h EE, fat oxidation, and plasma noradrenaline, may be prognostic markers for weight loss outcome in obese women.
The presence of hepatic steatosis was determined in 180 middle-aged male workers by ultrasonography and was found in 39 (22%) of them. Body mass index (BMI), systolic and diastolic blood pressure (BP) and serum levels of asparate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) were higher in the subjects with hepatic steatosis. Although the volume of alcohol consumed in a week did not differ between the subjects with and without hepatic steatosis, the hepatic steatosis was thought to relate to both increased body mass and alcohol consumption because the elevations of serum AST and gamma-GTP in the subjects depended largely on alcohol consumption but not on BMI. The results of 75 g oral glucose tolerance test showed a higher blood glucose at 120 minutes and a higher plasma immunoreactive insulin at baseline, 60 and 120 minutes in the subjects with hepatic steatosis, being adjusted for age, BMI and alcohol consumption. The significant association between serum gamma-GTP and BP, which had been often observed in alcohol consumers, was no longer significant after adjustment for plasma insulin levels whereas plasma insulin showed a significant association with BP. These results suggest the possibility that hypertension in alcohol consumers, and also in obese people, relates at least partly to hyperinsulinaemia associated with progression in hepatic steatosis.
Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.
The aim of the present study was to investigate whether eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) was responsible for the triglyceride-lowering effect of fish oil. In rats fed a single dose of EPA as ethyl ester (EPA-EE), the plasma concentration of triglycerides was decreased at 8 h after acute administration. This was accompanied by an increased hepatic fatty acid oxidation and mitochondrial 2,4-dienoyl-CoA reductase activity. The steady-state level of 2,4-dienoyl-CoA reductase mRNA increased in parallel with the enzyme activity. An increased hepatic long-chain acyl-CoA content, but a reduced amount of hepatic malonyl-CoA, was obtained at 8 h after acute EPA-EE treatment. On EPA-EE supplementation, both EPA (20:5n-3) and docosapentaenoic acid (DPA, 22:5n-3) increased in the liver, whereas the hepatic DHA (22:6n-3) concentration was unchanged. On DHA-EE supplementation retroconversion to EPA occurred. No statistically significant differences were found, however, for mitochondrial enzyme activities, malonyl-CoA, long-chain acyl-CoA, plasma lipid levels, and the amount of cellular fatty acids between DHA-EE treated rats and their controls at any time point studied. In cultured rat hepatocytes, the oxidation of [1-14C]palmitic acid was reduced by DHA, whereas it was stimulated by EPA. In the in vivo studies, the activities of phosphatidate phosphohydrolase and acetyl-CoA carboxylase were unaffected after acute EPA-EE and DHA-EE administration, but the fatty acyl-CoA oxidase, the rate-limiting enzyme in peroxisomal fatty acid oxidation, was increased after feeding these n-3 fatty acids. The hypocholesterolemic properties of EPA-EE may be due to decreased 3-hydroxy-3-methylglutaryl-CoA reductase activity. Furthermore, replacement of the ordinary fatty acids, i.e., the monoenes (16:1n-7, 18:1n-7, and 18:1n-9) with EPA and some conversion to DPA concomitant with increased fatty acid oxidation is probably the mechanism leading to changed fatty acid composition. In contrast, DHA does not stimulate fatty acid oxidation and, consequently, no such displacement mechanism operates. In conclusion, we have obtained evidence that EPA, and not DHA, is the fatty acid primarily responsible for the triglyceride-lowering effect of fish oil in rats.
The radical scavenging activity of Japanese edible seaweeds was screened by the DPPH (1-diphenyl-2-picrylhydrazyl) assay to evaluate the DPPH radical scavenging activity in organic extracts. The fresh brown alga Hijikia fusiformis showed the strongest DPPH radical scavenging activity, followed by Undaria pinnatifida and Sargassum fulvellum. The major active compound from Hijikia fusiformis in its acetone extract was identified as fucoxanthin by 13C-NMR spectroscopy.
Inflammation has been suggested as a risk factor for the development of atherosclerosis. Recently, some components of the insulin resistance syndrome (IRS) have been related to inflammatory markers. We hypothesized that insulin insensitivity, as directly measured, may be associated with inflammation in nondiabetic subjects.
We studied the relation of C-reactive protein (CRP), fibrinogen, and white cell count to components of IRS in the nondiabetic population of the Insulin Resistance Atherosclerosis Study (IRAS) (n=1008; age, 40 to 69 years; 33% with impaired glucose tolerance), a multicenter, population-based study. None of the subjects had clinical coronary artery disease. Insulin sensitivity (S(I)) was measured by a frequently sampled intravenous glucose tolerance test, and CRP was measured by a highly sensitive competitive immunoassay. All 3 inflammatory markers were correlated with several components of the IRS. Strong associations were found between CRP and measures of body fat (body mass index, waist circumference), S(I), and fasting insulin and proinsulin (all correlation coefficients >0.3, P<0.0001). The associations were consistent among the 3 ethnic groups of the IRAS. There was a linear increase in CRP levels with an increase in the number of metabolic disorders. Body mass index, systolic blood pressure, and S(I) were related to CRP levels in a multivariate linear regression model.
We suggest that chronic subclinical inflammation is part of IRS. CRP, a predictor of cardiovascular events in previous reports, was independently related to S(I). These findings suggest potential benefits of anti-inflammatory or insulin-sensitizing treatment strategies in healthy individuals with features of IRS.
C-reactive protein (CRP) is an inflammatory-response protein that is a strong, independent predictor of cardiovascular mortality. CRP is positively associated with body mass index (BMI). In this study, we investigated the effects of dynamic weight loss on CRP in 83 healthy, obese women (mean BMI, 33.8+/-0.4 kg/m(2); range, 28.2 to 43.8 kg/m(2)). Subjects were placed on very-low-fat, energy-restricted diets (5700 kJ, 15% fat) for 12 weeks. Weight, waist and hip circumferences, plasma lipids, glucose, and CRP were measured at baseline and after 12 weeks. CRP was positively associated with BMI (r=0.281, P=0.01) and waist circumference (r=0.278, P=0.01) but was not related to other atherosclerosis risk factors. BMI was significantly different between groups split above or below the median for CRP (34.8+/-0.6 kg/m(2) vs 33.0+/-0.5 kg/m(2), P=0.02). After 12 weeks, weight loss was 7.9+/-0.3 kg. CRP was significantly decreased by 26% (P<0.001), and a correlation was observed between weight loss and the change in CRP (r=0.309, P=0.005). The variance in the change in CRP was partly explained by initial CRP (13.6%), energy intake (5.4%), and percentage weight loss (4.6%, P=0.001). This study confirms recent observations that BMI is associated with CRP, a marker for low-grade systemic inflammation. Furthermore, we observed that CRP was lowered in proportion to weight loss.
Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes.
A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication.
There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration.
This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.
The physiological effects of 9cis,11trans,13cis-conjugated linolenic acid (9c,11t,13c-CLNA), one of the CLNA isomers, were studied in human hepatoma HepG2 cells. 9c,11t,13c-CLNA significantly decreased apolipoprotein B100 secretion compared with alpha-linolenic acid (alpha-LNA). The uptake of (14)C-oleate into newly synthesized cellular triacylglycerol was also decreased by 9c,11t,13c-CLNA more than by alpha-LNA treatment. This is the first study to show the hypolipidemic effect of 9c,11t,13c-CLNA.
Mitochondrial uncoupling protein 1 (UCP1) is usually expressed only in brown adipose tissue (BAT) and a key molecule for metabolic thermogenesis to avoid an excess of fat accumulation. However, there is little BAT in adult humans. Therefore, UCP1 expression in tissues other than BAT is expected to reduce abdominal fat. Here, we show reduction of abdominal white adipose tissue (WAT) weights in rats and mice by feeding lipids from edible seaweed, Undaria pinnatifida. Clear signals of UCP1 protein and mRNA were detected in WAT of mice fed the Undaria lipids, although there is little expression of UCP1 in WAT of mice fed control diet. The Undaria lipids mainly consisted of glycolipids and seaweed carotenoid, fucoxanthin. In the fucoxanthin-fed mice, WAT weight significantly decreased and UCP1 was clearly expressed in the WAT, while there was no difference in WAT weight and little expression of UCP1 in the glycolipids-fed mice. This result indicates that fucoxanthin upregulates the expression of UCP1 in WAT, which may contribute to reducing WAT weight.
It has been suggested that oxidative stress and endothelial dysfunction could play a role in the higher cardiovascular disease risk noted in the abdominally obese population.
The objective of this study was to describe the associations between abdominal fat accumulation, oxidative stress, and endothelial dysfunction in men.
A complete physical and metabolic profile was assessed in a group of 56 men covering a wide range of adiposity and plasma oxidized low-density lipoprotein (OxLDL), and soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and C-reactive protein concentrations were determined.
We found that abdominal visceral adipose tissue was positively associated with plasma OxLDL (r = 0.52; P < 0.0001) and C-reactive protein (r = 0.60; P < 0.0001) concentrations. We also found significant associations between plasma E-selectin levels and hyperinsulinemia (r = 0.39; P < 0.005) as well as with the homeostasis model assessment index of insulin resistance (r = 0.42; P < 0.005).
Our study showed that plasma OxLDL levels and low-grade systemic inflammation are increased in men with a high visceral adipose tissue accumulation. Furthermore, our results support the notion that insulin resistance is associated with endothelial activation. Overall, our observations give us further insights on the increased cardiovascular disease risk frequently noted among viscerally obese, insulin-resistant individuals.
Gamma-glutamyltransferase (GGT) has been associated with hypertension (HTN); however, the nature of this association remains unclear. GGT is a marker of alcohol consumption, but it is also related to the infiltration of fat in the liver (fatty liver). The association between GGT and HTN was examined in a 6-year longitudinal investigation among 1455 men and women who returned for the follow-up visit. Baseline variables included serum GGT, blood pressure, and anthropometric measures. Incident HTN was defined as blood pressure > or =140/90 or on antihypertensive medication at the follow-up visit. To eliminate individuals with potential liver pathology, analyses focused only on individuals with GGT within its normal range (n=897). Participants were divided in quintiles (Q) based on their baseline GGT levels. Multiple logistic regression analyses [odds ratio (95% confidence intervals)] revealed a significant association of GGT with incident hypertension [2.1 (1.1 to 4.0) Q5 versus Q1]. In subgroup analyses, GGT and HTN were significantly associated among both noncurrent and current drinkers, but only for participants above the median of anthropometric measures [eg, body mass index >26.4, 2.3 (0.9 to 5.7), waist circumference >86.1 cm, 3.7 (1.4 to 9.9), and abdominal height >19.8 cm, 3.1 (1.2 to 8.5), for Q5 versus Q1, in fully adjusted models]. These findings suggest that the association between GGT and hypertension is not caused solely by alcohol consumption and indicate that serum GGT, within its normal range, may predict hypertension among individuals with increased central fat distribution, suggesting that fatty liver may represent an important underlying mechanism for this association.
Nonalcoholic fatty liver diseases are often associated with obesity, insulin resistance, and excessive visceral fat accumulation. The aims of this study were (1) to evaluate the relationship between the severity of fatty liver and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to investigate the relationships of fatty liver with biochemical data and insulin resistance.
One hundred twenty-nine subjects (63 women) with fatty liver diagnosed by ultrasonography were enrolled. Subjects positive for hepatitis B virus, hepatitis C virus, or autoimmune antibodies and those whose alcohol intake was over 20 g/day were excluded. The visceral fat area at the umbilical level and the liver-spleen ratio were evaluated by computed tomography.
The severity of fatty liver evaluated by ultrasonography showed a significant positive relationship with the visceral fat area and waist circumstance (fatty liver severity: mild, 92.0 +/- 30.9 cm(2); moderate, 122.1 +/- 32.6 cm(2); severe, 161.0 +/- 48.4 cm(2); P < 0.0001). The visceral fat area and liver-spleen ratio were negatively correlated (r = -0.605, P < 0.0001). The severity of fatty liver showed strong positive relationships with serum aspartate aminotransferase, alanine aminotransferase, fasting plasma glucose, fasting plasma insulin, and insulin resistance. The severity of fatty liver was positively related to the visceral fat area in 49 nonobese subjects (body mass index <25).
The severity of fatty liver was positively correlated with visceral fat accumulation and insulin resistance in both obese and nonobese subjects, suggesting that hepatic fat infiltration in nonalcoholic fatty liver disease may be influenced by visceral fat accumulation regardless of body mass index.
This study examined the effect of dietary fucoxanthin or fucoxanthinol on the amount of docosahexaenoic acid (DHA) in the liver of KKAy mice, a model for obese/type II diabetes. In the first experiment, mice were fed diets containing crude fucoxanthin or glyceroglycolipid for 4 weeks. Results showed a significant increase in the level of DHA in mice fed 0.53% crude fucoxanthin, from 2.3% in control mice to 5.1% of fatty acid composition of total liver lipids. On the other hand, in mice fed crude glyceroglycolipid, the level of DHA as a proportion of total liver fatty acids remained unchanged. To clarify the enhancement of hepatic DHA, in the second experiment, KKAy mice were fed a diet containing purified fucoxanthin or its deacetylated derivative, fucoxanthinol. Results from a quantitative analysis using an internal standard showed that in mice fed 0.2% fucoxanthin, the amount of hepatic DHA was 2-fold higher than in control mice, whereas DHA levels in the small intestine remained unchanged. Furthermore, 0.2% fucoxanthinol led to 1.8- and 1.2-fold increases in the amount of hepatic DHA and arachidonic acid compared to control mice, respectively. These results indicate for the first time that dietary fucoxanthin and fucoxanthinol enhance the amount of DHA in the liver of KKAy mice.
Regional body fat distribution may represent an independent risk factor for several conditions, especially metabolic and cardiovascular diseases; recent findings have shown that abdominal fat accumulation can be an independent predictor of hepatic steatosis. Very few studies, mostly using selected clinical samples, have focused on the relationship between indices of abdominal visceral fat accumulation and the most commonly used biochemical liver tests, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT). The aim of the present study was to evaluate the relation between central fat accumulation, as assessed by abdominal height, relative weight, as determined by body mass index (BMI), and liver function tests (ALT, AST, and GGT) in a random sample of 2,704 residents of Erie and Niagara Counties in New York State, 35-80 years of age and free from known hepatic disease. Multiple linear regression models were used, with liver enzymes as dependent variables with abdominal height and BMI as independent variables, and the inclusion of several covariates (age, race, education, smoking status, pack-years of smoking, drinking status, and total ounces of ethanol in the past 30 days). Abdominal height was consistently a better correlate of ALT and GGT levels than BMI in both sexes. In addition, abdominal height was the most powerful independent predictor of ALT in both sexes as well as of GGT among women. In conclusion, these findings support a role for central adiposity independent from BMI in predicting increased levels of hepatic enzymes, likely as a result of unrecognized fatty liver.
Example 2: macroalgae and microalgae
- Ja Haugan
- T Aakemann
- Liaaen-Jensen
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