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Anti-obese action of raspberry ketone
Abstract
Raspberry ketone (4-(4-hydroxyphenyl) butan-2-one; RK) is a major aromatic compound of red raspberry (Rubus idaeus). The structure of RK is similar to the structures of capsaicin and synephrine, compounds known to exert anti-obese actions and alter the lipid metabolism. The present study was performed to clarify whether RK helps prevent obesity and activate lipid metabolism in rodents. To test the effect on obesity, our group designed the following in vivo experiments: 1) mice were fed a high-fat diet including 0.5, 1, or 2% of RK for 10 weeks; 2) mice were given a high-fat diet for 6 weeks and subsequently fed the same high-fat diet containing 1% RK for the next 5 weeks. RK prevented the high-fat-diet-induced elevations in body weight and the weights of the liver and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric). RK also decreased these weights and hepatic triacylglycerol content after they had been increased by a high-fat diet. RK significantly increased norepinephrine-induced lipolysis associated with the translocation of hormone-sensitive lipase from the cytosol to lipid droplets in rat epididymal fat cells. In conclusion, RK prevents and improves obesity and fatty liver. These effects appear to stem from the action of RK in altering the lipid metabolism, or more specifically, in increasing norepinephrine-induced lipolysis in white adipocytes.
... The motivation for these studies comes from the structural similarity of RK with capsaicin and synephrine, which are known to exert antiobesity effects . In 2005, Morimoto (Morimoto et al., 2005) first elucidated the influence of RK on obesity and demonstrated that RK supplementation decreased body weight gain, hepatic triglyceride content, and the weight of visceral adipose tissue (epididymis, retroperitoneum, and mesentery) in high-fat diet-induced obese mice. The author concluded that RK can prevent obesity and improve fatty liver by changing lipid metabolism, especially by increasing the effect of norepinephrine (NE) induced white adipocytes lipolysis (Morimoto et al., 2005). ...
... In 2005, Morimoto (Morimoto et al., 2005) first elucidated the influence of RK on obesity and demonstrated that RK supplementation decreased body weight gain, hepatic triglyceride content, and the weight of visceral adipose tissue (epididymis, retroperitoneum, and mesentery) in high-fat diet-induced obese mice. The author concluded that RK can prevent obesity and improve fatty liver by changing lipid metabolism, especially by increasing the effect of norepinephrine (NE) induced white adipocytes lipolysis (Morimoto et al., 2005). ...
... Model Treatment Major findings Morimoto et al. (2005) Mice HFD with 0%, 0.5%, 1%, or 2% (w/w) RK for 10 wk; HFD for 6 wk followed by HFD+1% RK for another 5 wk indicated that RK is bound to the active site of α-glucosidase and interacts with several key residues, which is a non-competitive, reversible, and rapid inhibition. The mechanisms that underlie the interaction between RK and α-glucosidase were attributed to the structural characteristics of hydroxybenzene ring. ...
Novel food and food compounds interventions have attracted a lot of attention nowadays for the prevention and treatment of metabolic diseases. Raspberry ketone (RK) is aromatic compound found within red fruits and berries, has been used as an over-the-counter product for weight loss. However, actually, the effect of RK on weight loss is still controversial, and the mechanism is largely unknown. Besides, in vivo and in vitro studies have demonstrated the beneficial effect of RK on the development of other metabolic diseases. In this review, we comprehensively highlighted the synthesis, bioavailability, and metabolism of RK, and summarized the progress made in our understanding of the potential biological activities of RK, including antiobesity, antidiabetes, cardioprotection, and hepatoprotection, as well as their underlying mechanisms. This paper provides a critical overview about the current findings and proposes the future studies in the area of RK on human health.
Practical applications
Raspberry ketone (RK) has been used for weight control for years, but this effect is controversial considering food intake. Additionally, RK is beneficial for T2DM, liver and heart injury. The underlying mechanisms of the protective effect of RK including accelerating fatty acid oxidation, balancing serum glucose level, anti-inflammation, antioxidant process, and so on. In this context, we provide a comprehensive analysis of the benefits of RK against many metabolic diseases and discuss the underlying molecular mechanisms. We hope our work will be helpful for further researches on RK and improve its public recognition.
... Of the many health benefits reported, the anti-obesity property of RK has gained the most popularity. Adding RK as a supplement to a weight loss plan is suggested to decrease the accumulation of fats around the abdominal organs and enhance fat burning efficiency [10]. Raspberry ketone has shown to stimulate the metabolism of white and brown adipose tissues via norepinephrine-induced lipolysis, inhibiting the absorption o dietary fat in the small intestine [11,12]. ...
... Of the many health benefits reported, the anti-obesity property of RK has gained the most popularity. Adding RK as a supplement to a weight loss plan is suggested to decrease the accumulation of fats around the abdominal organs and enhance fat burning efficiency [10]. Raspberry ketone has shown to stimulate the metabolism of white and brown adipose tissues via norepinephrine-induced lipolysis, inhibiting the absorption of dietary fat in the small intestine [11,12]. ...
... The mice also showed a partial decrease in hepatic triacylglycerol levels as well as increased lipolysis in response to norepinephrine in white adipose cells in vitro. This early study gave some indications towards the weightreducing and lipolysis effects of RK [10]. Another group studied the effect of RK on the expression and secretion of adiponectin, lipolysis, and fatty acid oxidation in 3T3-L1 mouse adipose cells. ...
Raspberry ketone (RK) is an aromatic phenolic compound naturally occurring in red raspberries, kiwifruit, peaches, and apples and reported for its potential therapeutic and nutraceutical properties. Studies in cells and rodents have suggested an important role for RK in hepatic/cardio/gastric protection and as an anti-hyperlipidemic, anti-obesity, depigmentation, and sexual maturation agent. Raspberry ketone-mediated activation of peroxisome proliferator-activated receptor-α (PPAR-α) stands out as one of its main modes of action. Although rodent studies have demonstrated the efficacious effects of RK, its mechanism remains largely unknown. In spite of a lack of reliable human research, RK is marketed as a health supplement, at very high doses. In this review, we provide a compilation of scientific research that has been conducted so far, assessing the therapeutic properties of RK in several disease conditions as well as inspiring future research before RK can be considered safe and efficacious with limited side effects as an alternative to modern medicines in the treatment of major lifestyle-based diseases.
... It is widely used as a fragrance in cosmetics and flavoring agent in foodstuff. Several reports have demonstrated its lipolytic and anti-obesity activities (Morimoto et al. 2005;Leu et al. 2018;Mehanna et al. 2018). In the present study, we induced obesity in mice by feeding them for 10 weeks on a high-fat diet. ...
... In the present study, we induced obesity in mice by feeding them for 10 weeks on a high-fat diet. Increases in body weight and fat storage was noted in accordance with the previously published reports (Morimoto et al. 2005;Mukai et al. 2016). In addition, we explored the possible adverse effects of consumption of RK during normal obese and health compromised obese condition in mice. ...
... RK decreased the body weight and this may be due to inhibition of pancreatic lipase enzyme activity and inhibition of intestinal absorption. Thus, the weight lowering effect observed in this study conforms with other reports that demonstrated weight reducing property of RK (Morimoto et al. 2005;Park 2010;Lopez et al. 2013). However, the retardation in weight gain during the 10-day study could also be due to loss of appetite in the groups given LPS and RK. ...
Raspberry ketone (RK)—an aromatic compound found mostly in red raspberries (Rubus idaeus) is widely used as an over the counter product for weight loss. The present study was conducted to determine adverse effects associated with RK in obese and health-compromised obese mice. Two sets of experiments were conducted on normal obese and health-compromised obese mice treated with RK for a duration of 10 days. Obese conditions were induced by feeding mice a high fat diet for 10 weeks, while the health compromised obese mouse model was developed by a single intraperitoneal injection of a nontoxic dose of lipopolysaccharide (LPS) (6 mg/kg) to obese mice. Results showed that RK (165, 330, and 500 mg/kg) under obese as well as health-compromised condition retarded the gain in body weights as compared to the control groups. RK at doses 330 and 500 mg/kg resulted in 67.6 and 50% mortality, respectively in normal obese mice and 70% mortality was observed in health-compromised obese mice treated with RK at 500 mg/kg. At higher doses deaths were observed earlier than those given lower doses of RK. Significant elevations in blood alanine transaminase (ALT) were also observed with RK treatment in obese mice. Blood glucose levels were significantly elevated in all groups of mice treated with RK. This study suggests that higher doses of RK may cause adverse effects in health compromised conditions. Under these conditions, prolonged use of RK, especially in high doses, may pose a health hazard.
... Red raspberry (3%) for 3-weeks reduced endogenous oxidative DNA damage in CD1-Mice (Aiyer et al., 2008). Raspberry ketones (0.5, 1 and 2%) for 6-weeks decreased body weight and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric) in male ICR mice fed a high-fat diet (Morimoto et al., 2005). ...
... Using a starch assay, red raspberry extract inhibited -amylase and -glucosidase (McDougall et al., 2005). Hepatic triacylglycerol content was attenuated and norepinephrineinduced lipolysis was increased with raspberry ketones (0.5, 1 and %) for 6-weeks of obesityinduced ICR mice (Morimoto et al., 2005). ...
Metabolic syndrome (MetS) is major public health concern. Diet can play a major role in the prevention and/or progression of the MetS. At 8 weeks of age, male obese Zucker rat (OZR) and their lean littermates (LZR) were placed on a control or an 8% w/w whole red raspberry (WRR)-enriched diet for 8 weeks. Circulating levels of inflammatory cytokines and their gene expression in the liver and adipose tissue were evaluated. Several lipid markers were measured in the plasma, liver and adipose tissue. The expression of eight genes related to lipid metabolism were evaluated, both in liver and adipose tissue. Phenylephrine (Phe)-induced vasoconstriction and acetylcholine (Ach)-induced vasorelaxation were measured in aortic rings in the presence or absence of L-N-monomethyl-arginine (L-NMMA) and mefenamic acid (MFA). Prostanoid levels were measured in the aortic effluent. Vascular function related gene were analyzed in the aorta. Plasma levels of interleukin-6 (IL-6) decreased in the OZR consuming a WRR diet compared to the OZR-C (p
... RK mitigated ovariectomy-induced weight gain [12,14], and reduced high-fat diet induced nonalcoholic steatohepatitis in rats [15]. Adulteration of diet with RK has shown to prevent weight gain [16,17], however, the strong sensory profile of RK could have potentially affected food intake. Previous work from our lab supports the preventative actions of oral gavage administration of RK against weight gain and fat accumulation in a high-fat diet induced obesogenic environment [18]. ...
... RK has reported effects on weight gain due to an obesogenic diet in male mice when administered by admixture in the diet [16,17] or, in our previous studies, by oral gavage [18]. In these studies differences in weight gain were observed after three to five weeks of exposure to RK. ...
Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a popular nutraceutical used for weight management and appetite control. We sought to determine the physiological benefits of RK on the meal patterns and cardiovascular changes associated with an obesogenic diet. In addition, we explored whether the physiological benefits of RK promoted anxiety-related behaviors. Male and female C57BL/6J mice were administered a daily oral gavage of RK 200 mg/kg, RK 400 mg/kg, or vehicle for 14 days. Commencing with dosing, mice were placed on a high-fat diet (45% fat) or low-fat diet (10% fat). Our results indicated that RK 200 mg/kg had a differential influence on meal patterns in males and females. In contrast, RK 400 mg/kg reduced body weight gain, open-field total distance travelled, hemodynamic measures (i.e., reduced systolic blood pressure (BP), diastolic BP and mean BP), and increased nocturnal satiety ratios in males and females. In addition, RK 400 mg/kg increased neural activation in the nucleus of the solitary tract, compared with vehicle. RK actions were not influenced by diet, nor resulted in an anxiety-like phenotype. Our findings suggest that RK has dose-differential feeding and cardiovascular actions, which needs consideration as it is used as a nutraceutical for weight control for obesity.
... Chetone del lampone. Il cosiddetto "chetone del lampone" corrisponde al 4-(4-idrossifenil)-2-butanone, un composto aromatico estratto dal lampone rosso (Rubus idaeus) (23). Le prove a sostegno dell'attività di questa sostanza come agente lipolitico provengono soprattutto da studi preclinici su cavia, che suggeriscono un suo possibile ruolo nella promozione della lipolisi norepinefrino-indotta e nell'ossidazione degli acidi grassi (23,24). ...
... Il cosiddetto "chetone del lampone" corrisponde al 4-(4-idrossifenil)-2-butanone, un composto aromatico estratto dal lampone rosso (Rubus idaeus) (23). Le prove a sostegno dell'attività di questa sostanza come agente lipolitico provengono soprattutto da studi preclinici su cavia, che suggeriscono un suo possibile ruolo nella promozione della lipolisi norepinefrino-indotta e nell'ossidazione degli acidi grassi (23,24). I dati sulla sicurezza del "chetone del lampone" sono quasi del tutto assenti, con potenziali effetti avversi (cardiotossicità, alterazioni dello sviluppo e della riproduzione) indicati da modelli predittivi basati sui dati di studi di laboratorio (25). ...
Background. Overweight and obesity are conditions characterized by a growing epidemiological trend.
Objective. The present review aims to collect evidence on the efficacy and safety of remedies derived from medicinal herbs and mushrooms commonly used for weight loss.
Results. Various remedies, grouped on the basis of their mechanism of action, have been analyzed and discussed.
Conclusions. Overall, the most interesting integrative remedies which favor weight loss in overweight or obese subjects seem to be Garcinia cambodia, Camellia sinensis, green coffee, Amorphophallus konjac, chitosan, and Phaseolus vulgaris, acting through different mechanisms on metabolism, nutrient absorption and the sensation of hunger. Further studies are needed to better evaluate the efficacy and safety profile of weight-loss supplements.
CITE AS: Antonelli, M., & Donelli, D. (2019). Medicinal herbs and mushrooms for weight loss: an overview. Pharmanutrition and Functional Foods, 4(4), 12–17.
... In 1965, raspberry ketone was designated as a generally A C C E P T E D M A N U S C R I P T 8 recognized as safe (GRAS) food additive and is listed as a synthetic flavoring substance/adjuvant by the U.S. Food and Drug Administration (FDA) [13]. Based on the structural similarity to other bioactive phenolic compounds, however, raspberry ketone has been examined for anti-obesity potential in rodents and in in vitro systems [8,[14][15][16][17][18][19]. In vivo rodent studies suggest that raspberry ketone may be effective at preventing the metabolic alterations associated with excessive caloric intake, rather than reversing the metabolic effects caused by obesity [16,17,20]. ...
... Based on the structural similarity to other bioactive phenolic compounds, however, raspberry ketone has been examined for anti-obesity potential in rodents and in in vitro systems [8,[14][15][16][17][18][19]. In vivo rodent studies suggest that raspberry ketone may be effective at preventing the metabolic alterations associated with excessive caloric intake, rather than reversing the metabolic effects caused by obesity [16,17,20]. The preventative capacity of raspberry ketone is supported by in vitro studies demonstrating that raspberry ketone acts by inhibiting expression of genes related to adipogenesis, to prevent adipocyte differentiation and lipid accumulation [14,15,18,19,21]. ...
Red raspberries (Rubus idaeus) contain numerous phenolic compounds with purported health benefits. Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone) is a primary raspberry flavor phenolic found in raspberries and is designated as a synthetic flavoring agent by the Food and Drug Administration. Synthetic raspberry ketone has been demonstrated to result in weight loss in rodents. We tested whether phenolic-enriched raspberry extracts, compared with raspberry ketone, would be more resilient to the metabolic alterations caused by an obesogenic diet. Male C57BL/6J mice (8 weeks old) received a daily oral dose of vehicle (VEH; 50% propylene glycol, 40% water, and 10% dimethyl sulfoxide), raspberry extract low (REL; 0.2 g/kg), raspberry extract high (REH; 2 g/kg), or raspberry ketone (RK; 0.2 g/kg). Coincident with daily dosing, mice were placed on a high-fat diet (45% fat). After 4 weeks, REH and RK reduced body weight gain (approximately 5%-9%) and white adipose mass (approximately 20%) compared with VEH. Hepatic gene expression of heme oxygenase-1 and lipoprotein lipase was upregulated in REH compared with VEH. Indirect calorimetry indicated that respiratory exchange ratio (CO2 production to O2 consumption) was lower, suggesting increased fat oxidation with all treatments. REH treatment increased total ambulatory behavior. Energy expenditure/lean mass was higher in REH compared with REL treatment. There were no treatment differences in cumulative intake, meal patterns, or hypothalamic feed-related gene expression. Our results suggest that raspberry ketone and a phenolic-enriched raspberry extract both have the capacity to prevent weight gain but differ in the preventative mechanisms for excess fat accumulation following high-fat diet exposure.
... Its anti-obesity action is related to its structural similarity to epinephrine. It mediates β-adrenergic stimulation, enhancing lipolysis from white adipocytes and thermogenesis in brown adipocytes (Morimoto et al. 2005). RK held GRAS (Generally Recognized as Safe) status since 1965 for use as a natural flavouring agent. ...
In this article, we designed one-step economic eco-harmonious microwave-assisted procedure to prepare nitrogen-doped carbon dots. We selected egg white as a cheap glycoprotein-based carbon source without the assistance of any chemicals. The synthetic process requires only 3 min during which carbonization and nitrogen doping are realized at the same time. The fabricated carbon dots were characterized for particle size, structure and photoluminescence behaviour. The nanodots were amorphous carbon-rich naturally nitrogen-doped particles with plentiful attached hydrophilic functional groups. They had average particle size 2.98 ± 1.57 nm, emitted strong blue fluorescence and showed excitation-dependant emission behaviour. What is more, the practical use of this system for raspberry ketone determination in commercially available weight loss dietary supplement product is demonstrated successfully. In ethylene glycol medium, the addition of raspberry ketone enhances the emission intensity of the synthesized carbon dots. The effect of reaction time and solvent was investigated. After optimization, the intensity enhancement was linear to the amount of raspberry ketone added to the assay solution in the concentration range of 100–1000 ng/ml, with detection and quantitation limits of 15.10 and 45.45 ng/ml, respectively. The method was validated in accordance to International Conference on Harmonization (ICH) guidelines and further applied to raspberry ketone capsules showing excellent results.
Graphical abstract
... Raspberry ketone (4-(4-hydroxyphenyl)-2-butanone; RK) is one of the major natural phenolic ketone compounds present in European red raspberry (Rubus idaeus L.) (9,10), and may possess lipolytic and anti-obesity effects (Fig. 1). Several studies in mice have reported that RK prevents increases in body weight and the weight of the liver and visceral adipose tissues (epididymal, retroperitoneal, and mesenteric) induced by a high-fat diet (11)(12)(13). Rhododendrol (4-(4-hydroxyphenyl)-2-butanol; ROH) is present in Betula platyphylla and Acer nikoense Maximowicz (14,15). When administered orally to mammals, RK is metabolized via several pathways (16). ...
Obesity is a serious medical condition worldwide, and a major risk factor for type 2 diabetes, metabolic syndrome, cancer and cardiovascular disease. In addition to changes in dietary habits and physical activity, consuming supplements to maintain good health and prevent obesity is important in modern society. Raspberry ketone (RK) is a natural phenolic ketone found in the European red raspberry (Rubus idaeus L.) and is hypothesized to prevent obesity when administered orally. The present study found that RK was reduced to rhododendrol (ROH) in human liver microsomes and cytosol. The present study investigated whether the metabolite ROH had anti‑adipogenic effects using mouse 3T3‑L1 cells. The effects of ROH or RK on lipid accumulation during differentiation of 3T3‑L1 pre‑adipocyte into adipocyte were determined using Oil Red O staining. CCAAT enhancer‑binding protein α (C/EBPα) and peroxisome proliferator‑activated receptor γ (PPARγ) mRNA and protein expression were examined using reverse transcription‑quantitative PCR and western blotting analysis, respectively. The present study revealed that ROH suppressed lipid accumulation in the cells, similar to RK. In addition, ROH suppressed the mRNA expression levels of C/EBPα and PPARγ in 3T3‑L1 adipocytes. Furthermore, ROH suppressed PPARγ protein expression in 3T3‑L1 adipocytes. These findings suggested that ROH is an active metabolite with an anti‑adipogenic effect, which may contribute to the anti‑obesity effect of orally administered RK. The present study indicated that it is important to understand the biological activity of the metabolites of orally administered compounds.
... Raspberry ketones are structurally related to a stimulant compound called synephrine and are thought to possibly activate the β-adrenergic receptors. Animal studies suggest that raspberry ketones enable weight loss through various mechanisms, including norepinephrine-induced lipolysis [4]. At least one case of coronary vasospasm has been associated with raspberry ketone intake [5]. ...
A 32-year-old female with no cardiac risk factors was admitted for treatment of a perianal abscess. During her hospital stay, she had a pulseless electrical activity arrest with a return of spontaneous circulation after one round of cardiopulmonary resuscitation (CPR). After transfer to the Intensive Care Unit (ICU), the patient had polymorphic ventricular tachycardia (PVT) requiring defibrillation shock. Her PVT was resistant to medical interventions. She was shocked a total of 33 times before her arrhythmia was terminated by passing a temporary transvenous pacemaker with overdrive pacing. After an extensive review of her history and presentation, no clear cause of her resistant arrhythmia was identified, however, she was found to have recently started taking over-the-counter weight loss supplements containing raspberry ketones which is a potentially cardiotoxic ingredient.
... Raspberry ketone and esters, aldehydes, alcohols, terpenes, ketones and pyrazines together form a complex mixture of volatile aroma components of red raspberries. Raspberry ketone can regulate body weight, prevent obesity, and alleviate obesity-induced hyperlipidemia in vivo [19]. Besides, raspberry ketones can increase insulin secretion and possesses hypoglycemic properties [20]. ...
Nonalcoholic fatty liver disease (NAFLD) is characterized by diffused hepatocyte bullous fat in the liver, which is not caused by alcohol or drugs like amiodarone and tamoxifen. Presently, no drug is approved for NAFLD treatment. Therefore, it’s important to extract effective components from natural plants to alleviate NAFLD. In this study, we extracted and purified raspberry ketone, a natural phenolic compound from red raspberry ( Rubus ideaus L.) by an ultrasonic-assisted ethanol extraction method. The structure of red raspberry ketone (RRK) was determined using Fourier-transform infrared spectroscopy and the purity of RRK was found as 80.06 ± 1.19%. After 28 days of intragastric administration of RRK, the bodyweight of NAFLD model rats decreased significantly (p < 0.05). Besides, the levels of low-density lipoprotein cholesterol, total cholesterol, and total triglyceride (TG) decreased and the content of high-density lipoprotein cholesterol in serum increased drastically. Moreover, the level of liver damage indicators (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase) and the levels of glucose, insulin, free-fatty acid, tumor necrotic factor-α in the liver decreased distinctly. The levels of TG and malondialdehyde in the liver decreased, whereas the levels of superoxide dismutase, total glutathione, and glutathione peroxidase drastically increased. We also found that RRK reduced the uneven size of liver cells and blurred boundaries of hepatic lobules, and alleviated hepatic steatosis and inflammation caused by NAFLD. We inferred that RRK could relieve NAFLD progression by regulating glucose and lipid metabolism and alleviating oxidative stress in vivo. This study sheds new light on the use of RRK as a functional food for NAFLD prevention.
... RK has a structure resembling those of capsaicin and synephrine and can prevent HFD-induced obesity (117). 3T3-L1 adipocytes treated with 10 µM RK presented with elevated FAO and inhibition of lipid accumulation (118). ...
Epidemic obesity is contributing to increases in the prevalence of obesity-related metabolic diseases and has, therefore, become an important public health problem. Adipose tissue is a vital energy storage organ that regulates whole-body energy metabolism. Triglyceride degradation in adipocytes is called lipolysis. It is closely tied to obesity and the metabolic disorders associated with it. Various natural products such as flavonoids, alkaloids, and terpenoids regulate lipolysis and can promote weight loss or improve obesity-related metabolic conditions. It is important to identify the specific secondary metabolites that are most effective at reducing weight and the health risks associated with obesity and lipolysis regulation. The aims of this review were to identify, categorize, and clarify the modes of action of a wide diversity of plant secondary metabolites that have demonstrated prophylactic and therapeutic efficacy against obesity by regulating lipolysis. The present review explores the regulatory mechanisms of lipolysis and summarizes the effects and modes of action of various natural products on this process. We propose that the discovery and development of natural product-based lipolysis regulators could diminish the risks associated with obesity and certain metabolic conditions.
... metabolism in obese mice by increasing the level of irisin in circulation. [6,7] In an in vitro study, FNDC5/irisin enhanced adipocyte browning, with the cell morphology showing a higher density of mitochondria and multilocular lipid droplets. [6] Therefore, FNDC5/irisin may be a key protein in the treatment of metabolic diseases with exercise. ...
Obesity is a global health problem and a risk factor for cardiovascular diseases and cancers. Exercise is an effective intervention to combat obesity. Fibronectin type III domain containing protein 5 (FNDC5)/irisin, a myokine, can stimulate the browning of white adipose tissue by increasing uncoupling protein 1 (UCP1) expression, and therefore may represent a link between the beneficial effects of exercise and improvement in metabolic diseases. Thus, upregulating the endogenous expression of FNDC5/irisin by administering medication would be a good approach for treating obesity. Herein, we evaluated the efficacy of raspberry ketone (RK) in inducing FNDC5/irisin expression and the underlying mechanisms. The expression of brown fat-specific proteins (PR domain containing 16 (PRDM16), CD137, and UCP1), heme oxygenase-1 (HO-1), FNDC5, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in differentiated 3T3-L1 adipocyte was analyzed by western blotting or immunofluorescence. The level of irisin in the culture medium was also assayed using an enzyme-linked immunosorbent assay kit. Results showed that RK (50 μM) significantly induced the upregulation of FNDC5 protein in differentiated 3T3-L1 adipocytes; however, the irisin level in the culture media was unaffected. Moreover, RK significantly increased the levels of PGC1α, brown adipocyte markers (PRDM16, CD137, and UCP1), and HO-1. Furthermore, the upregulation of PGC1α and FNDC5 and the browning effect induced by RK were significantly reduced by SnPP or FNDC5 siRNA, respectively. In conclusion, RK can induce FNDC5 protein expression via the HO-1 signaling pathway, and this study provides new evidence for the potential use of RK in the treatment of obesity.
... The berry flavor of RK with a low odor threshold is used as a food additive to create various aromas such as cherry, strawberry, kiwi and other fruits (Beekwilder et al., 2007;Bredsdorff et al., 2015;Sun et al., 2021). The alleged health benefits of RK include weight reduction (Morimoto et al., 2005;Wang et al., 2012) and skin lightening (Harada et al., 2008) and it is in high demand in the supplements and cosmetics industries (Milke et al., 2020;Vandamme and Soetaert, 2002). As the demand for RK is second only to vanillin, the potential of RK in the natural flavor market RK is 6-10 million Euros (Feron and Wache 2005). ...
The demand for raspberry ketone (RK) as a plant-based natural flavoring agent is high, but natural RK is one of the most expensive flavor compounds due to its limited content in plants. Here, we produced RK de novo from simple carbon sources in Escherichia coli. We genetically engineered E. coli metabolism to overproduce the metabolic precursors tyrosine and p -coumaric acid and increase RK production. The engineered E. coli produced 19.3- and 1.9 g/L of tyrosine and p -coumaric acid from glucose, respectively. The p -coumaric acid CoA ligase from Agrobacterium tumefaciens and amino acid substituted benzalacetone synthase of Rhemu palmatum (Chinese rhubarb) were overexpressed in E. coli overproducing p -coumaric acid . The overexpression of fabF , encoding β-ketoacyl-acyl carrier protein synthetase II increased intracellular malonyl-CoA, the precursor of benzalacetone synthase for RK biosynthesis, and improved RK production. Fed-batch cultures given glucose as a carbon source produced 62 mg/L of RK under optimized conditions. Our production system is inexpensive and does not rely on plant extraction; thus, it should significantly contribute to the flavor and fragrance industries.
... 11,30,31 In this review, data on the most relevant bioactive compounds of the plant, the seed, and raspberry fruit were analyzed, among which anthocyanins and ketones stood out. 32,33 The consumption of raspberries subjected to processing such as juice, puree, and bread or preservation methods such as frozen, lyophilization has shown positive effects on the regulation of glucose concentrations and some serum lipids, demonstrating these effects both in acute consumption as chronic. 16,25,27 Studies in animal models indicate that lyophilized raspberry added to the diet of rodents also shows hypoglycemic and lipid-lowering effects such as increased insulin receptor activity, improving tissue sensitivity, reducing its requirements, and stabilizing blood glucose levels. ...
Raspberry production and consumption have increased in recent years due to its polyphenol content such as anthocyanins and ketones, bioactive compounds that have been studied to reduce blood glucose levels and stabilize the blood lipid profile. The objective of this study was to systematically recover and review scientific evidence regarding the consumption of raspberry or its bioactive compounds and the action mechanisms involved in the hypoglycemic and lipid-lowering effects they present. Original articles from in vitro and in vivo enzyme inhibition studies, animal models, and human clinical studies were compiled in PubMed, Web of Science, and Science Direct databases. Studies showed satisfactory results regarding blood glucose level reduction after consumption of frozen or lyophilized raspberry, infusion of raspberry leaves, seed oil, as well as compounds, extracted from the fruit by inhibiting enzymes such as α-glucosidase and dipeptidyl peptidase-4 (DPP-4) and other mechanisms that increase insulin production and insulin sensitivity. However, regarding the lipid-lowering effect, the results were heterogeneous, mainly in terms of stabilization in triglyceride levels. However, a reduction in cholesterol and low-density lipoprotein levels is reported, as well as an increase in high-density lipoproteins. According to the results, raspberry can be included in the nonpharmacological treatment of hyperglycemia and dyslipidemias; however, further research is considered necessary.
... Therefore, naturally-derived raspberry ketone is one of the most expensive flavor compounds (US$ 3000/kg), which is as valuable a flavoring agent as natural vanillin . In addition to its flavoring applications, raspberry ketone has been utilized in the cosmeceutical industry for its weight-loss and skin-whiting properties (Morimoto et al., 2005;Lin et al., 2011). ...
Raspberry ketone is one of the characteristic flavors of raspberry fruits, and it is an important and expensive ingredient in the flavor and fragrance industries. It is present at low levels in plant tissues, and its occurrence is limited to a few taxa. In this context, the stable production of nature-identical raspberry ketone using heterologous synthesis in plants hosts has recently garnered the attention of plant biochemists. In this study, we demonstrate the rational switching of the metabolic flow from anthocyanin pigments to volatile phenylbutanoid production via the phenylpropanoid pathway. This shift led to the efficient and stable production of raspberry ketone and its glycosides via heterologous expression of the biosynthetic enzymes benzalacetone synthase (BAS) and raspberry ketone/zingerone synthase 1 (RZS1) in the transgenic tobacco (Nicotiana tabacum ‘Petit Havana SR-1’). Additionally, we achieved improved product titers by activating the phenylpropanoid pathway with the transcriptional factor, production of anthocyanin pigment 1 (PAP1), from Arabidopsis thaliana. We further demonstrated another metabolic-flow switching by RNA interference (RNAi)-mediated silencing of chalcone synthase (CHS) to increase pathway-intermediate p-coumaroyl-CoA in transgenic tobacco for raspberry-ketone production. The redirection of metabolic flux resulted in transgenic lines producing 0.45 μg/g of raspberry ketone and 4.5 μg/g, on the fresh weight basis, of its glycosides in the flowers. These results suggest that the intracellular enforcement of endogenous substrate supply is an important factor while engineering the phenylpropanoid pathway. This strategy might be useful for the production of other phenylpropanoids/polyketides that are produced via the pathway-intermediate p-coumaroyl-CoA, in tobacco plants.
... Raspberry ketone (RK; 4-(4-hydroxyphenyl)-butan-2-one) is a key phenolic aroma compound naturally present in red raspberries (Rubus idaeus), and it is generally recognized as safe (GRAS) as a flavoring agent added to cosmetics and food products [21]. In recent years, RK has been marketed in the US as a dietary supplement for weight control given its efficacy in limiting fat accumulation in white adipose tissue in rodents [22][23][24]. Our previous bioavailability studies on RK and its structurally associated phenolic metabolites in mice provide important insight into its metabolism and pharmacokinetic behaviors [25]. ...
Raspberry ketone (RK), a major flavor compound in red raspberries, has been marketed as a popular weight-loss dietary supplement with high potential in accumulating fatty tissues. However, challenges in extracting and characterizing phenolic compounds in fatty tissues persist due to the excessively high lipid content and the vast concentration ranges of phenolic constituents accumulating in adipose tissues. In this work, we reported a high-throughput sample preparation method for RK and 25 related phenolic compounds in white adipose tissues using an improved micro-scale QuEChERS (quick, efficient, cheap, easy, rugged and safe) approach with enhanced matrix removal (EMR)-lipid cleanup in 96-well plates, followed by UHPLC-QqQ-MS/MS analysis. The absolute recovery at the extraction step was 73–105%, and achieved 71–96% at the EMR cleanup step. The EMR cleanup removed around 66% of total lipids in the acetonitrile extract as profiled by UHPLC-QTOF-MS/MS. The innovative introduction of a reversed-phase C18 sorbent into the extract significantly improved the analytes’ recovery during SpeedVac drying. The final accuracy achieved 80–120% for most analytes. Overall, this newly developed and validated method could serve as a powerful tool for analyzing RK and related phenolic compounds in fatty tissues.
... Related studies have shown that red raspberry phytochemical extracts [22] had many pharmacological effects. Raspberry ketone had the ability of increase norepinephrine-induced lipolysis in white adipocytes, which could prevent and improve obesity and fatty liver [23]. The extract of red raspberry fruit showed antiinflammatory properties to reduce the degree of bone resorption, soft tissue swelling, and osteophyte formation, preventing articular destruction in treated animals [24]. ...
Background:
Colorectal cancer (CRC) is among the top three gastrointestinal malignancy in morbidity and mortality. The abnormal activation of Wnt/β-catenin pathway is considered to be a key factor in the occurrence and development of CRC. Novel inhibitor discovery against key factor in WNT pathway is important for CRC treatment and prevention.
Methods:
Cell proliferation was detected after hydroxyphenyl butanone treatment in human colorectal cancer HCT116, LOVO, and normal colonic epithelial NCM460 cells. Colony formation, cell invasion ability, and cell cycle were detected with and without GSK-3β knockdown.
Results:
Hydroxyphenyl butanone induces cycle arresting on G1-S phase of colorectal cancer cell line through GSK3β in Wnt/β-catenin pathway and inhibits malignant biological manifestations of cell proliferation, colony formation, and invasion. The inhibition in the high concentration group is stronger than that in the low concentration group, and the antitumor effect is different for different tumor cells. Under the same concentration of natural hydroxyphenyl butanone, the inhibition on normal colonic epithelial cells is significantly lower than that on tumor cells. The natural hydroxyphenyl butanone with medium and low concentration could promote the proliferation of normal colonic epithelial cells.
Conclusion:
This study illustrated natural hydroxyphenyl butanone as new inhibitor of GSK3β and revealed the mechanisms underlying the inhibitory effects in colorectal cancer.
... In addition, raspberry ketone is utilized as an attractant in insect baits (Perez 1983;Metcalf et al. 1983;Deifel 1989) and as a component in perfumes (Dumont et al. 1996;Farwick et al. 2019), whereas further applications in cosmetic industry, e.g., as skin whitening or hair growth inducing agent, remain controversial (Harada et al. 2008;Kim et al. 2016). Other publications promote dose-dependent health benefits with regard to an anti-obese effect (Morimoto et al. 2005;Park 2015;Tsai et al. 2017;Zhao et al. 2019;Mir et al. 2019) or suggest medical applications due to its antioxidant and anti-inflammatory potential (Parmar and Tripathi 1991;Khan et al. 2018;Fouad et al. 2019;Mohamed et al. 2020;Hamdy et al. 2020). ...
Raspberry ketone is a widely used flavor compound in food and cosmetic industry. Several processes for its biocatalytic production have already been described, but either with the use of genetically modified organisms (GMOs) or incomplete conversion of the variety of precursors that are available in nature. Such natural precursors are rhododendrol glycosides with different proportions of ( R )- and ( S )-rhododendrol depending on the origin. After hydrolysis of these rhododendrol glycosides, the formed rhododendrol enantiomers have to be oxidized to obtain the final product raspberry ketone. To be able to achieve a high conversion with different starting material, we assembled an alcohol dehydrogenase toolbox that can be accessed depending on the optical purity of the intermediate rhododendrol. This is demonstrated by converting racemic rhododendrol using a combination of ( R )- and ( S )-selective alcohol dehydrogenases together with a universal cofactor recycling system. Furthermore, we conducted a biocatalytic cascade reaction starting from naturally derived rhododendrol glycosides by the use of a glucosidase and an alcohol dehydrogenase to produce raspberry ketone in high yield.
Key points
• LB-ADH, LK-ADH and LS-ADH oxidize (R)-rhododendrol
• RR-ADH and ADH1E oxidize (S)-rhododendrol
• Raspberry ketone production via glucosidase and alcohol dehydrogenases from a toolbox
Graphical abstract
... A large body of experimental studies revealed the improving effects of flavonoids on serum levels of gonadotropins and testosterone as well as testicular tissue and function (Ahangarpour et al., 2015). Aromatic compounds found in raspberries can increase norepinephrine (Morimoto et al., 2005). Norepinephrine, in turn, induces the release of GnRH from the hypothalamus and ultimately, FSH and LH secretion from the anterior pituitary gland by increasing NO synthesis (Selvage and Johnston, 2004;Całka, 2006). ...
Objective:
Protective effects of raspberry (Rubus fruticosus L.) fruit extract on pituitary-gonadal axis and testicular tissue in diabetic male rats, were investigated.
Materials and methods:
Sixty male rats were divided into control, sham (saline treated), streptozotocin (STZ)-diabetic, and STZ-diabetic animals treated with 50, 100 and 200 mg/kg/day of raspberry extract. After 4 weeks, blood samples were obtained and left testes were removed and prepared for histopathological studies. Serum levels of Luteinizing hormone (LH), Follicle stimulating hormone (FSH), testosterone, Nitric oxide (NO), and malondialdehyde (MDA), as well as superoxide dismutase (SOD) and catalase (CAT) activity level were assayed. Sperm number and motility in the epididymis samples were measured. Data were analyzed using ANOVA (one-way analysis of variance).
Results:
Serum levels of LH, FSH and MDA significantly increased in diabetic rats, however, treatment with the extract significantly reversed the alterations. Serum levels of testosterone and NO, activity of SOD and CAT, and sperm number and motility significantly decreased and severe destruction of testicular histology was observed in diabetic animals while treatment with the extract significantly reversed the pathologic alterations observed in diabetic rats. According to the results, 100 and 200 mg/kg of the extract were able to effectively reverse the diabetes complications.
Conclusion:
Our findings demonstrated that the fruit extract of raspberry has protective effects on male reproductive system in diabetic rats partially due to its improving effects on NO system, and SOD and CAT activity.
... RK was first identified in 1903, and the chemical structure of this compound isolated from raspberries was determined in 1951 [45]. The structure of RK resembles that of capsaicin and synephrine, compounds that have anti-obesity effects and modulate lipid metabolism [46]. When structural similarities of these three compounds have been noted, extensive anti-obesity studies have been conducted with RK [47][48][49]. ...
Oxidative stress is closely linked to various diseases, and many studies have been conducted to determine how to reduce this stress. In particular, efforts are being made to find potential antioxidants from natural products. Studies have shown that raspberry ketone (RK; 4-(4-hydroxyphenyl)-2-butanone) has various pharmacological activities. This review summarizes the antioxidant activities of RK and their underlying mechanisms. In several experimental models, it was proven that RK exhibits antioxidant properties through increasing total antioxidant capacity (TAC); upregulating antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT); and improving lipid peroxidation. In conclusion, research about RK’s antioxidant activities is directly or indirectly related to its other various physiological activities. Further studies at the clinical level will be able to verify the value of RK as an effective antioxidant, functional health food, and therapeutic agent.
... Raspberry ketone 11 is the primary aroma compound of red raspberries and it is an important industrial product with antifungal, antiobesity and cardioprotective activities. [62][63][64] Its synthesis holds interest 65,66 and it was also obtained here using the Pd@Hf-MOF-808 catalyst starting with 4-hydroxybenzaldehyde by the aldol condensation-double bond hydrogenation one-pot sequence. In this way, raspberry ketone 11 was isolated in a good yield of 82% and the method further stands out as an appropriate strategy for the preparation of important intermediates and final compounds in fine chemistry. ...
... In the current study, the HFD/STZ rats showed an increment in their body weight (BW), which is consistent with several previous studies [47][48][49][50][51][52] . The increased BW could be attributed to the consumption of a diet rich in energy in the form of saturated fats, which deposit in various body fat pads and decrease energy expenditure as compared to the NFD rats 53 . ...
Introduction: Clinical and epidemiological studies suggest that patients who are overweight or
obese are more at risk in developing glucose intolerance (G/I) and insulin resistance (I/R)
leading to type 2 diabetes (T2DM) and cardiovascular disease.
Aim of work: Assess the dynamic contribution of visfatin in the development of obesity and/or
diabetes and demonstrate their possible molecular mechanism(s) from side and from another
side, modulate role of Raspberry ketone (RK) as weight management supplement and illustrate
their possible molecular mechanism(s).
Materials and Methods: Eighty adult rats were divided into eight groups (10 rats for each
group, G); G1: Normal Control Group (Normal diet); G2: Diabetic Control Group (received
streptozotocin 35 mg/kg); G3: Obese Control Group (received high fat diet, HFD); G4: Obese
Diabetic Control Group, G5: Raspberry ketone Control Group (received 500 mg/kg), G6:
Diabetic rats treated with Raspberry ketone; G7: Obese rats treated with Raspberry ketone and
G8: Obese Diabetic rats treated with Raspberry ketone to assess the study’s aims, their effect
was determined on body weight, OGTT, glucose homeostasis (glucose, insulin, HOMA-IR),
oxidative stress markers, cytoglobin, visfatin and liver histopathology.
Results: RK caused weight loss, corrected the disturbed glucose and insulin homeostasis,
Furthermore, RK increased hepatic content of glutathione (GSH), while decreased hepatic
content of malonaldialdehyde (MDA). RK also up regulated hepatic protein expression of
cytoglobin, while down regulated hepatic mRNA expression of visfatin.
Conclusion: This study assessed the involvement of visfatin and cytoglobin in obese diabetic
rats and modulated the role of RK through the efficient rebalance of glucose homeostasis, I/R,
the redox status and liver histopathology.
... Arylated ketones are important motifs found in bioactive natural products and are important synthetic intermediates of many industrial products like pharmaceuticals, cosmetics, or agrochemicals. [1][2][3][4][5][6][7] In this article, a kind of particular arylated ketones viz 1,3-diaryl butanones has been paid attention. These ketones are useful as important precursors for the preparation of NK2 and NK3 receptor antagonists for the treatment of asthma, [8] GABAB receptor agonist (R)-baclofen hydrochloride, [9,10] matrix metalloprotease inhibitors for tumor cell invasion, [11] anti-inflammatory agents, [12] inhibitors of stomach acid secretion, [13] and as a solvent for inks and lacquers. ...
A tandem reaction for the simple construction of 1,3-diaryl butanones from acetophenones was developed. Anhydrous HI was generated in situ by the promotion of the [Rh]- complex with molecular hydrogen and iodine. The acetophenones undergo aldol reactions by anhydrous HI firstly, and then hydrogenation reactions by the same [Rh]-complex to generate the corresponding 1,3-diaryl butanones in one pot.
... pudding, yogurt or sweets [1,2]. In addition, its presumed activity as an anti-obesity or skinwhitening agent, drew consumers interest, although a potential toxicity of this compound for humans has not yet been clarified [2][3][4][5][6]. ...
Background:
The phenylbutanoid 4-(4-hydroxyphenyl)butan-2-one, commonly known as raspberry ketone, is responsible for the typical scent and flavor of ripe raspberries. Chemical production of nature-identical raspberry ketone is well established as this compound is frequently used to flavor food, beverages and perfumes. However, high demand for natural raspberry ketone, but low natural abundance in raspberries, render raspberry ketone one of the most expensive natural flavoring components.
Results:
In this study, Corynebacterium glutamicum was engineered for the microbial synthesis of the character impact compound raspberry ketone from supplemented p-coumaric acid. In this context, the NADPH-dependent curcumin/dihydrocurcumin reductase CurA from Escherichia coli was employed to catalyze the final step of raspberry ketone synthesis as it provides a hitherto unknown benzalacetone reductase activity. In combination with a 4-coumarate: CoA ligase from parsley (Petroselinum crispum) and a monofunctional benzalacetone synthase from Chinese rhubarb (Rheum palmatum), CurA constitutes the synthetic pathway for raspberry ketone synthesis in C. glutamicum. The resulting strain accumulated up to 99.8 mg/L (0.61 mM) raspberry ketone. In addition, supplementation of other phenylpropanoids allowed for the synthesis of two other naturally-occurring and flavoring phenylbutanoids, zingerone (70 mg/L, 0.36 mM) and benzylacetone (10.5 mg/L, 0.07 mM).
Conclusion:
The aromatic product portfolio of C. glutamicum was extended towards the synthesis of the flavoring phenylbutanoids raspberry ketone, zingerone and benzylacetone. Key to success was the identification of CurA from E. coli having a benzalacetone reductase activity. We believe, that the constructed C. glutamicum strain represents a versatile platform for the production of natural flavoring phenylbutanoids at larger scale.
... The cytokine tumor necrosis factor alpha (TNF-a) was reported to elevate lipolytic activity in differentiated human preadipocytes [75] and in humans in vivo [76]. Besides inhibiting apoptosis, several phytochemicals stimulate lipolysis in adipocytes such as a-mangostin, g-mangostin, and resveratrol [77,78] and 4-(4-hydroxyphenyl)butan-2-one by regulating HSL in high fat diet (HFD) fed mice [79]. ...
... Raspberry ketone [(4-hydroxyphenyl) butan-2-one], a natural phenolic compound, is present naturally in raspberries; it has been used many years ago in many industries including perfumes, cosmetics and as a flavoring agent in the food industry [13]. Raspberry ketone showed an anti-obese effect via increasing fatty acid oxidation and lipolysis [14,15]. Besides, it has anti-inflammation activity through inhibiting the nuclear kappa-β activation pathway [16] and antiandrogenic activity [17]. ...
Objective: To investigate the molecular mechanisms of the anti-obese effect of raspberry ketone against high-fat diet fed rats.
Methods: Fifty adult male rats were randomly assigned to receive a standard diet, a high fat diet, and the high-fat diet and 0.5%, 1% or 2% raspberry ketone. Body weight, biochemical parameters and gene expression of CCAAT enhancer-binding protein (C/EBP)δ, fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), peroxisome proliferator-activated receptor alpha (PPAR-α), hormone-sensitive lipase (HSL) and hepatic carnitine palmitoyltransferase 1 A (CPT1A) were investigated.
Results: Body weight, blood glucose, insulin, total lipids, triacylglycerols, total cholesterol and low-density lipoprotein cholesterol were increased in high-fat diet fed rats. These high fat diet-induced changes were attenuated by treatment with raspberry ketone. High-density lipoprotein cholesterol was decreased in highfat diet fed rats but increased in rats treated with raspberry ketone. Molecular investigations showed induction of gene expression of C/EBP-δ, FAS, ACC, CPT1A and inhibition of gene expression of PPAR-α and HSL in high-fat diet fed rats as compared with control. Raspberry ketone treament reversed these changes except CPT1A.
Conclusions: Raspberry ketone can prevent obesity induced by a high-fat diet in rats by induction of the expression of enzymes, controlling lipolysis and fatty acids β oxidation as well as inhibition of gene expressions of adipogenic factors.
... It is presumed that RK might influence the lipid metabolism in ways similar to capsaicin and synephrine. The effects of RK on obesity and lipid metabolism were examined by Morimoto et al. [11]. ...
Aims
A Fourier Transform Infrared (FT-IR) spectrometric method was developed for the rapid, direct measurement of Raspberry Ketone (RK) and Caffeine (CAF) in a nutraceutical formulation.
Methods
Conventional KBr-spectra and KBr+0.5 mg Microcrystalline Cellulose (MCC)-spectra were used as the basis for a better determination of active substances in the nutraceutical formulation. A calibration model was developed using caffeine and raspberry ketone standards of varying concentrations in the mid-infrared region (4000-400 cm ⁻¹ ). The Beer-Lambert law was used in data processing.
Results
The results indicate that FT-IR spectrometry is applicable to the analytical quantification of RK and CAF in the nutraceutical formulation.
Conclusion
The method proposed is simple, precise and not time-consuming compared to the chromatographic methods that are cited in the literature. Quantification is performed in about 10-15 minutes, including sample preparation and spectral acquisition.
... Raspberry ketones give a fruity aroma to foods, cosmetics and scents for perfumes, Chie Morimoto et al was described in their study on "Anti-obese action of raspberry ketone" that structure of raspberry ketone is similar to synephrine and capsaicin. Both synephrine and capsaicin are known to have actions that are performed as anti-obese [7]. The study in rats was shown to both prevent, as well as improve, the incidence of fatty liver and obesity. ...
Over the years, the biological activities of medicinal plants and their compounds have gained considerable research interest due to their specific functional compounds, The novel long chain aliphatic hydroxyl ketones reported from medicinal plants over the past years are increasingly being recognized as new active compounds. The extraction of such active compounds have also attracted special attention recent years. Potent biologically active long chain aliphatic hydroxy ketones, from medicinal plants have been shown to play significant role towards prevention of degenerative diseases such as cancer, inflammation, arthritis, diabetes, parkinson"s disease, alzheimer"s disease, and certain other neurodegenerative disorders. The novel chemical entities drived from medicinal plants as active components for can be used in many industrial applications such as functional foods, pharmaceuticals and nutraceuticals. This review intends to explore such thirty eight long chain aliphatic hydroxy ketones isolated from twenty one different medicinal plants during last fifty years (1960-2010) for their possible application as anticancer, antimicrobial and antioxidant activites.
... RK not only has been applied in the food and cosmetic industries for its unique fragrance properties (Beekwilder et al. 2007), but also in recent years has drawn attention in the pharmaceutical industry for its medicinal value (Kim et al. 2016). In particular, RK has beneficial effects on lipid metabolism and can help to prevent obesity and lose weight (Morimoto et al. 2005;Wang et al. 2012). The odor threshold of RK is approximately 1-10 ppb (Larsen and Poll 1992), and when used as an additive in food or other products, its concentration ranges from 5 to 50 ppm. ...
Raspberry ketone is an important ingredient in the flavor and fragrance industries. Due to its low content in fruits and vegetables, the production of natural raspberry ketone using heterologous synthesis in microbial strains is recently attracting increased attention. In this work, a heterologous pathway to produce raspberry ketone from p-coumaric acid, including 4-coumarate: CoA ligase (4CL), benzalacetone synthase (BAS), and raspberry ketone/zingerone synthase (RZS1) from plants, was successfully assembled in Escherichia coli. When the RZS1 gene was introduced into E. coli and co-expressed with two other genes, the intermediate 4-hydroxybenzylidene acetone in the pathway was almost completely transformed into a raspberry ketone. Substituting TB medium for M9 medium increased raspberry ketone titers by 3–4 times. Furthermore, the heterologous pathway was partitioned into two modules; module one produced p-coumaroyl-CoA from p-coumaric acid by 4CL, and module two produced raspberry ketone from coumaroyl-CoA by the action of BAS and RZS1. Optimizing the balanced expression of the two modules, it was shown that moderate expression of module one and high expression of module two was the best combination to enhance raspberry ketone production. The engineered strain CZ-8 reached 90.97 mg/l of raspberry ketone, which was 12 times higher than previously reported. In addition, the preferred approach of the heterologous pathway was related to the heterologous genes from different sources; for example, 4CL from Arabidopsis thaliana seemed to be more suitable for raspberry ketone production than that from Petroselinum crispum. This work paves an alternative way for future economic production of natural raspberry ketone.
... Additionally, HCA acts as a competitive inhibitor of the citrate cleavage enzyme, ATP citrate lyase, which is involved in the initial steps of cholesterol and fatty acid biosynthesis [31]. The effect of RK, on the other hand, is mediated by enhancing the adipose tissue metabolism and by hindering the absorption of dietary fats from the small intestine [32]. Taken together, GC and RK combination, via targeting both dietary fat absorption and cholesterol/fatty acids synthesis and catabolism, could provide credit to the superior hypolipidmic and anti-obesity effects that override that of the single agents. ...
Aim
Obesity is a continually growing pandemic leading to many diseases that affect the overall quality of life. The widely marketed Garcinia cambogia (GC) and Raspberry ketone (RK) were used in this study. Despite their known dietetic effect, however, the metabolomic/signaling pathways involved in this effect are not fully elucidated. Hence, our study comprehends the possible trajectories of their combination against obesity and insulin resistance in addition to exploring their combination merit.
Materials and methods
Adult male Wistar rats were divided into 5 groups; viz., normal diet (ND), high fat fructose diet (HFFD), HFFD+GC (600mg/kg), HFFD+RK (55mg/kg) and HFFD+GC+RK. To assess our aim, we determined their effect on body weight, IPGTT, glucose homeostasis (glucose, insulin, HOMA IR), lipid profile parameters and SREBP-1c, oxidative stress markers, insulin and leptin signaling pathways (p-IRS-1/p-AKT/GLUT-4, and leptin/STAT-3), as well as liver and adipose tissue histopathology.
Results
GC/RK combinationcaused weight loss, corrected the disturbed glucose and insulin homeostasis, raised serum levels of HDL anddecreased all other lipid profile parameters. They also increased Nrf-2 expression, ad GSH, as well as p-IRS-1/p-Akt/GLUT-4 cue, while they decreased MDA, leptin/STAT-3 and SREBP-1c content compared to the HFFD group. Furthermore, the GC/RK combination abolished apoptosis, fatty changes and inflammation in hepatocytes and decreased sclerotic blood vessels and congestion in adipose tissue.
Conclusion
Our study highlights the involvement ofp-IRS-1/p-Akt/GLUT-4, leptin/STAT-3 and SREBP-1c signaling trajectories in the beneficial combination of GC and RK, besides, the efficient rebalance of the redox status, insulin resistance and tissue fat deposition confirmed histopathologically.
Background: Raspberry ketone (RK), derived from red raspberry fruit (Rubus idaeus, family Rosaceae), is a reported potent antiobesity agent. This study aims to investigate method development, validation, and in vitro and in vivo pharmacokinetics in rats. Materials & methods: LC-MS/MS was used to conduct method development, validation, stability, and oral PK samples of RK in plasma analyses. Results: RK was highly soluble in Tris buffer and stable in gastrointestinal fluids as well as plasma. Rat liver microsomal stability of RK in phase I and II studies was 84.96 ± 2.39 and 69.98 ± 8.69%, respectively, after 60 min. Intestinal permeability was 4.39 ± 1.37 × 10-5 cm/s. Maximal concentration was 1591.02 ± 64.76 ng/ml, which was achieved after 1 h (time to maximal concentration), and absolute oral bioavailability was 86.28%. Conclusion: Pharmacokinetic data serve as a keystone for preclinical and clinical adjuvant therapy.
Salmonella enterica is an important foodborne pathogen that causes gastroenteritis and systemic infection in humans and livestock. Salmonella biofilms consist of two major components—amyloid curli and cellulose—which contribute to the prolonged persistence of Salmonella inside the host. Effective agents for inhibiting the formation of biofilms are urgently needed. We investigated the antibiofilm effect of Raspberry Ketone (RK) and its mechanism of action against Salmonella Typhimurium 14028 using the Congo red agar method, Calcofluor staining, crystal violet method, pellicle assay, and the TMT-labeled quantitative proteomic approach. RK suppressed the formation of different types of Salmonella biofilms, including pellicle formation, even at low concentrations (200 µg/mL). Furthermore, at higher concentrations (2 mg/mL), RK exhibited bacteriostatic effects. RK repressed cellulose deposition in Salmonella biofilm through an unknown mechanism. Swimming and swarming motility analyses demonstrated reduced motility in RK-treated S. Typhimurium. Proteomics analysis revealed that pathways involved in amyloid curli production, bacterial invasion, flagellar motility, arginine biosynthesis, and carbohydrate metabolism, were targeted by RK to facilitate biofilm inhibition. Consistent with the proteomics data, the expressions of csgB and csgD genes were strongly down-regulated in RK-treated S. Typhimurium. These findings clearly demonstrated the Salmonella biofilm inhibition capability of RK, justifying its further study for its efficacy assessment in clinical and industrial settings.
Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is a synthetic flavoring agent and dietary supplement for weight control. This study investigated the metabolic signature of oral doses of RK that prevent weight gain or promote loss of righting reflex (LORR) in C57Bl/6J mice. Daily RK 200 mg/kg prevented high-fat diet (HFD; 45% Kcal fat) fed weight gain (∼8% reduction) over 35 days. RNA-seq of inguinal white adipose tissue (WAT) performed in males revealed 12 differentially expressed genes. Apelin (Apln) and potassium voltage-gated channel subfamily C member (Kcnc3) expression were elevated with HFD and normalized with RK dosing, which was confirmed by qPCR. Acute RK 640 mg/kg produced a LORR with a <5 min onset with a >30 min duration. Acute RK 200 mg/kg increased gene expression of Apln, Kcnc3, and nuclear factor erythroid 2-related factor 2 (Nrf2), but reduced acetyl-COA carboxylase (Acc1) and NAD(P)H quinone dehydrogenase 1 (Nqo1) in inguinal WAT. Acute RK 640 mg/kg elevated interleukin 6 (Il 6) and heme oxygenase 1 (Hmox1) expression, but reduced Nrf2 in inguinal and epididymal WAT. Our findings suggest that RK has a dose-dependent metabolic signature in WAT associated with either weight control or LORR.
Malina właściwa (Rubus idaeus L.) to krzew rosnący głównie w strefie umiarkowanej. Owoce maliny wyróżniają się doskonałym aromatem i czystą rubinową barwą; nadają się do konsumpcji i przetwórstwa. Surowcem leczniczym wykorzystywanym w przemyśle farmaceutycznym jest owoc maliny (Rubi idaei fructus) dojrzewający od lipca do października oraz liść maliny (Rubi idaei folium), zbierany wiosną i latem. Surowiec pozyskuje się z upraw i ze stanu naturalnego. Owoc maliny zawiera witaminy, kwasy organiczne, antocyjany, a liście są bogate w garbniki i flawonoidy. Surowce wykazują działanie ściągające, antyseptyczne, przeciwgorączkowe i wspomagające pracę układu pokarmowego.
Tertiary bicyclic phosphines derived from (R)-(+)-limonene provided efficient palladium catalysts for Heck cross-coupling reactions. Overall, high yields of the desired aryl alkenes products were obtained for cross-coupling of sterically and electronically diverse substrates. The efficiency of the catalysts was further demonstrated in the synthesis of commercial ketones, such as raspberry ketone and its derivatives.
Human gastrointestinal microbiota are known for the keto-reductive metabolism of small-molecule pharmaceuticals; however, the responsible enzymes remain poorly understood. Through in vitro biochemical assays, we report the identification of enzymes encoded in the genome of Clostridium bolteae that can reduce the ketone groups of nabumetone, hydrocortisone, and tacrolimus. The homologues to a newly identified enzyme (i.e., DesE) are potentially widely distributed in the gut microbiome. The selected enzymes display different levels of activities against additional chemicals such as two dietary compounds (i.e., raspberry ketone and zingerone), chemotherapeutic drug doxorubicin, and its aglycone metabolite doxorubicinone. Thus, our results expand the repertoire of enzymes that can reduce the ketone groups in small molecules and could serve as the basis for future personalized medicine approaches.
Plants produce myriad aroma compounds—odorous molecules that are key factors in countless aspects of the plant's life cycle, including pollinator attraction, and communication within and between plants. For humans, aroma compounds convey accurate information on food type, and are vital for assessing the environment. The phenylpropanoid pathway is the origin of notable aroma compounds, such as raspberry ketone and vanillin. In the last decade, great strides have been made in elucidating this pathway, with the identification of numerous aroma‐related biosynthetic enzymes and factors regulating metabolic shunts. These scientific achievements, together with public acknowledgment of aroma compounds’ medicinal benefits and growing consumer demand for natural products, are driving the development of novel biological sources for wide‐scale, eco‐friendly and inexpensive production. Microbes and plants that are readily amenable to metabolic engineering are garnering attention as suitable platforms for achieving this goal. In this review, we discuss the importance of aroma compounds from the perspectives of humans, pollinators and plant–plant interactions. Focusing on vanillin and raspberry ketone, which are of high interest to the industry, we present key knowledge on the biosynthesis and regulation of phenylalanine‐derived aroma compounds, describe advances in the adoption of microbes and plants as platforms for their production, and propose routes for improvement.
Uncoupling protein 1 (UCP1) in brown or beige adipocytes is a mitochondrial protein that is expected to enhance whole-body energy expenditure. For the high-throughput screening of UCP1 transcriptional activity regulator, we established a murine inguinal white adipose tissue-derived Ucp1-luciferase reporter preadipocyte line. Using this reporter preadipocyte line, 654 flavor compounds were screened, and a novel Ucp1 expression-inducing compound, 5-methylquinoxaline, was identified. Adipocytes treated with 5-methylquinoxaline showed increased Ucp1 mRNA expression levels and enhanced oxygen consumption. 5-methylquinoxaline induced Ucp1 expression through peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and 5-methylquinoxaline-induced PGC1α activation seemed to be partially regulated by its phosphorylation or deacetylation. Thus, our Ucp1-luciferase reporter preadipocyte line is a useful tool for screening of Ucp1 inductive compounds.
Raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] is a natural aromatic compound found in raspberries and other fruits. Raspberry ketone (RK) is synthetically produced for use as a commercial flavoring agent. In the United States and other markets, it is sold as a dietary supplement for weight control. The potential of RK to reduce or prevent excessive weight gain is unclear and could be a convergence of several different actions. This study sought to determine whether acute RK can immediately delay carbohydrate hyperglycemia and reduce gastrointestinal emptying. In addition, we explored the metabolic signature of chronic RK to prevent or remedy the metabolic effects of diet-induced weight gain. In high-fat diet (HFD; 45% fat)-fed male mice, acute oral gavage of RK (200 mg/kg) reduced hyperglycemia from oral sucrose load (4 g/kg) at 15 min. In HFD-fed female mice, acute oral RK resulted in an increase in blood glucose at 30 min. Chronic daily oral gavage of RK (200 mg/kg) commencing with HFD access (HFD_RK) for 11 weeks resulted in less body weight gain and reduced fat mass compared with vehicle treated (HFD_Veh) and chronic RK starting 4 weeks after HFD access (HFD_RKw4) groups. Compared with a control group fed a low-fat diet (LFD; 10% fat) and dosed with vehicle (LFD_Veh), glucose AUC of an oral glucose tolerance test was increased with HFD_Veh, but not in HFD_RK or HFD_RKw4. Apelin ( Apln) gene expression in epididymal white adipose tissue was increased in HFD_Veh, but reduced to LFD_Veh levels in the HFD_RK group. Peroxisome proliferator activated receptor alpha ( Ppara) gene expression was increased in the hepatic tissue of HFD_RK and HFD_RKw4 groups. Overall, our findings suggest that long term daily use of RK prevents diet-induced weight gain, normalizes high-fat diet-induced adipose Apln , and increases hepatic Ppara expression.
Although Dietary supplements are readily accessible and extensively used worldwide, they are inadequately regulated and consumers are victims of manufacturers' fraud. Thus, quality regulations are required to ensure safety of products available to the public. We propose the first native spectrofluorimetric quality control assay of raspberry ketone, a popular dietary supplement ingredient for weight loss. This work relies on the constant wavelength synchronous scan of the Raspberry Ketone native fluorescence, overcoming the demerits of conventional excitation/ emission spectra. For the best measurement conditions, several parameters were optimized including Δλ value, diluting solvent, medium pH and the effect of surfactants/ macromolecules. In aqueous medium (Δλ = 110 nm), a linear relationship exists between synchronous fluorescence intensity at peak maximum 405.6 nm and solution concentration in the range 300-1500 ng/mL. Method sensitivity was recorded with LOD and LOQ values 60.63 and 183.72 ng/mL; respectively. Validation was done in accordance to International Conference on Harmonization (ICH) guidelines. This simple procedure was successfully applied to the analysis of Raspberry Ketone in commercially available dietary supplement capsules with average recovery 98.67% ± 1.74 and further extended to weight variation testing following the official United States Pharmacopeial (USP) guidelines. Finally, green assessment was done using the ''Analytical Eco-scale'' tool. The total score was 89/100 points revealing excellent greenness of our proposal. Our proposal is simple, eco-friendly and cheap. It can be conveniently adopted for routine quality control practices especially in developing countries.
Non-alcoholic fatty liver disease is a major risk factor of the metabolic syndrome (MetS). The effect of whole red raspberry (WRR) consumption on lipid metabolism was investigated in the obese Zucker rat (OZR), a model for the MetS. Male OZRs (n = 16) and their lean littermates (lean Zucker rat) (n = 16) at 8 weeks of age were placed on a control or an 8% WRR-enriched diet for 8 weeks. Plasma triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), and non-HDL-C levels, and hepatic concentration of TG were measured. The expression of nine genes related to lipid metabolism was evaluated, both in liver and adipose tissue. A WRR-enriched diet reduced plasma cholesterol and HDL-C and increased plasma TG, while it decreased hepatic TG accumulation in the OZR. The OZR assigned to a WRR exhibited upregulation of microsomal triglyceride transfer protein (Mttp) and downregulation of fatty acid synthase (Fas) expression in the liver. Results showed a decrease in accumulation of liver TG and gene expression modulation of enzymes and transcription factors associated with lipid metabolism, suggesting a possible hepatoprotective role of a WRR-enriched diet.
This paper reports a one-pot synthesis of 5-[2-(4-methoxyphenyl)ethyl]-1H-pyrazole-3-carboxylates via cyclocondensation of 1,1,1-trichloro-4-methoxy-6-(4-methoxyphenyl)hex-3-en-2-one with hydrazine hydrochloride in ROH (R = Me, Et, n-Pr, i-Pr, i-Bu, i-Am, hexadecyl) under conventional and microwave heating. Yields are comparable in both methods, but under MW heating the reaction proceeds faster. The antioxidant activity of the compounds was measured using DPPH radical scavenging assay. It was observed, that the increase of the alcohol chain length decreases the antioxidant potential of the raspberry ketone derived molecular system.
In this thesis, we focus on the application of xanthate based radical chemistry for the synthesis of ketones, esters and β2-amino acids derivatives. This research overcomes many drawbacks associated with alkylation of ketones and esters when using enolate method, and complement the methods of dialkylation of unsaturated ketones. The xanthate transfer process also offers a convergent route to potential bioactive amino acids.We firstly summarize the utility and synthetic strategies of amino acids, then we describe a convergent route to β2-amino acids derivatives by adopting the xanthate transfer process. The xanthate can bear either an ester or free carboxylic acid group. When the α-xanthyl-β-amino ester is used as starting xanthate, almost all reactions were performed neat and provided the desired adducts in good to excellent yield. When the xanthate was bearing a free acid group, the addition to hetero-rings was accompanied with spontaneous decarboxylation to afford the N-protected heteroarylethylamines. In some cases, the unexpected vinyl products were separated and the plausible mechanism is also discussed.Then we briefly introduce the previously reported methods for alkylation of ketones, and then move on to our own research. By replacing enolates and enolate equivalents with α-ketonyl radicals, many disadvantages of alkylation of ketones such as aldol condensation, lack of regioselectivity, O-alkylation and polyalkylation can be minimized. Then we focus on the dialkylation of α, β-unsaturated ketones. In contrast with traditional ionic methods which have to use organocopper and alkyl halides, our new method incorporates both ionic and radical process which avoid the use of aforementioned organometallic agents and alkyl halides. It is noteworthy that the Michael addition step was significantly affected by stereochemistry while the radical addition step was little affected. Based on this methodology, various dialkylated cyclopentanones were rapidly synthesized including ring-fused compounds which are commonly present in natural products. Finally, in order to generalize the alkylation of carbonyl compounds, α-alkylation of esters was also investigated. In the scope extension section, we test the radical additions to different functionalized alkenes. All reactions proceeded smoothly and show a broad functional group tolerance. Reactions using lactones as substrates were also performed with the same conditions and were shown to be equally efficient.In summary, we used this xanthate transfer process as a powerful tool to synthesize many useful ketones, esters and amino acid derivatives. This metal-free method features mild reaction conditions, excellent functional group compatibility and good substrate scope which we anticipate will be, especially useful in the late-stage functionalization of natural products and drugs.
Raspberry ketone (RK; [4-(4-hydroxyphenyl)-2-butanone]) is used by the food and cosmetic industry as a flavoring agent. RK is also marketed as a dietary supplement for weight maintenance and appetite control. The purpose of the study was to characterize the acute feeding suppression with RK (64-640 mg/kg) by oral gavage in male and female C57BL/6J mice. Cumulative 24 h food intake was reduced at 200 mg/kg (24% feeding suppression) in males and reliably reduced at 640 mg/kg (49-77% feeding suppression). Feeding suppression was not associated with pica behavior over the range of doses or conditioned taste aversion. In a separate experiment, a single oral gavage of RK (640 mg/kg) resulted in approximate 43% mortality rate (6 out 14 male mice) within 2 days. Atrophy of white adipose tissue, splenic abnormalities, and thymus involution were noted after 2 to 4 days after oral gavage RK. Total white blood cell count, lymphocytes, monocytes, eosinophils were significantly lower, while mean red blood cells, hemoglobin, and hematocrit were significantly higher with RK treatment. Our findings indicated a dose-dependent feeding suppression with acute RK, but doses that reliable suppress food intake are associated with pathological changes.
Raspberry ketone (RK) (4-(4-hydroxyphenyl)-2-butanone) is the major compound responsible for the characteristic aroma of red raspberries, and has long been used commercially as a flavoring agent and recently as a weight loss supplement. A targeted UHPLC-QqQ-MS/MS method was developed and validated for analysis of RK and 25 associated metabolites in mouse plasma and brain. Dispersion and projection analysis and central composite design were used for method optimization. Random effect analysis of variance was applied for validation inference and variation partition. Within this framework, repeatability, a broader sense of precision, was calculated as fraction of accuracy variance, reflecting instrumental imprecision, compound degradation and carry-over effects. Multivariate correlation analysis and principle component analysis were conducted, revealing underlying association among the manifold of method traits. R programming was engaged in streamlined statistical analysis and data visualization. Two particular phenomena, the analytes’ background existence in the enzyme solution used for phase II metabolites deconjugation, and the noted liability of analytes in pure solvent at 4 ℃ vs. elevated stability in biomatrices, were found critical to method development and validation. The approach for the method development and validation provided a foundation for experiments that examine RK metabolism and bioavailability.
Electrospinning and electrospraying are versatile techniques for the production of nano- to micro-scale fibers and particles. Over the past 2 decades, significant progresses have been made to advance the fundamental understandings of these electrohydrodynamic processes. Researchers have investigated different polymeric and non-polymeric substrates for producing submicron electrospun/electrosprayed materials of unique morphologies and physicochemical properties. This chapter provides an overview on the basic principles of electrospinning and electrospraying, highlighting the effects of key processing and solution parameters. Electrohydrodynamic phenomena of edible substrates, including polysaccharides (xanthan, alginate, starch, cyclodextrin, pullulan, dextran, modified celluloses, and chitosan), proteins (zein, what gluten, whey protein, soy protein, gelatin, etc.), and phospholipids are reviewed. Selected examples are presented on how ultrafine fibers and particles derived from these substrates are being exploited for food and nutraceutical applications. Finally, the challenges and opportunities of the electrostatic methods are discussed.
Excessive fat accumulation in hypertrophied adipocytes lead to chronic inflammation, oxidative stress and dysregulated adipokines secretion. In this study, we investigated the ability of raspberry fruit extract (RBE) to mitigate adipose tissue dysfunction using hypertrophied 3T3-L1 adipocytes. The obtained results showed that RBE decreased intracellular ROS generation in hypertrophied adipocytes by enhancing expression of antioxidant defense enzymes SOD, catalase, and GPx, and inhibiting an oxidant enzyme NADPH oxidase 4. Moreover, RBE reduced lipid accumulation accompanied by increased lipid mobilization. RBE significantly inhibited LPL, aP2, FAS and PLIN mRNA expression, and enhanced the expression of HSL. Furthermore, RBE exhibited a high anti-inflammatory potential by down-regulation the expression of pro-inflammatory mediators (IL-6, TNF-α, IL-1β, MCP-1 and leptin), and counteracted the decrease in adiponectin and IL-10 expression. Raspberry fruit could be potentially valuable dietary ingredient towards mitigating adverse metabolic consequences of fat cell hypertrophy, thus reducing the risk of metabolic disorders.
Objectives
Research has shown that berries may have the ability to reverse, reduce, or slow the progression of behavioral dysfunction associated with aging and neurodegenerative disease. In contrast, high-energy and high-fat diets (HFD) may result in behavioral deficits like those seen in aging animals. This research examined whether red raspberry (Rubus ideaus) mitigates the effects of HFD on mouse brain and behavior.
Methods
Eight-week-old mice consumed a HFD (60% calories from fat) or a control diet (CD) with and without 4% freeze-dried red raspberry (RB). Behavioral tests and biochemical assays of brain tissue and serum were conducted.
Results
After 12 weeks on the diets, mice fed CD and HFD had impaired novel object recognition, but mice on the RB-supplemented diets did not. After approximately 20 weeks on the diets, mice fed HFD + RB had shorter latencies to find the escape hole in the Barnes maze than the HFD-fed mice. Interleukin (IL)-6 was significantly elevated in the cortex of mice fed HFD; while mice fed the CD, CD + RB, and HFD + RB did not show a similar elevation. There was also evidence of increased brain-derived neurotrophic factor (BDNF) in the brains of mice fed RB diets. This reduction in IL-6 and increase in BDNF may contribute to the preservation of learning and memory in HFD + RB mice.
Conclusion
This study demonstrates that RB may protect against the effects HFD has on brain and behavior; however, further research with human subjects is needed to confirm these benefits.
Ghosts of isolated fat cells take up α-aminoisobutyric acid (AIB) by a saturable and partially energy-dependent transport
process. Of several amino acids tested, methionine and alanine were the most effective in inhibiting influx and stimulating
efflux of AIB, indicating that the transport of these amino acids and AIB is shared by a common carrier-mediated system in
the plasma membrane of ghosts.
The uptake of AIB was stimulated by sodium ion, inhibited by ouabain, and diminished in the absence of potassium ion in the
incubation medium. The initial rate of AIB influx was not correlated to the initial rate of potassium influx. The results
suggest that the capacity of ghosts to accumulate and maintain a steady state content of AIB is a function of the potassium
and sodium gradients across the plasma membrane but is not directly linked to active sodium-potassium transport. Sodium-potassium
transport is probably the major energy-requiring process involved in the accumulation of AIB.
Insulin, adrenocorticotropin, and epinephrine did not alter the rate of uptake or the steady state levels of AIB in preparations
of ghosts that are sensitive, with respect to glucose transport or metabolism, to the effects of these hormones.
Numerous synthetic agonists selectively stimulate β3-adrenoceptors (ARs). The endogenous catecholamines, noradrenaline and adrenaline, however, stimulate all the β-AR subtypes, and no selective physiological agonist for β3-ARs has been described so far. The aim of this study was to investigate whether any naturally occurring amine can stimulate selectively β3-ARs. Since activation of lipolysis is a well-known β-adrenergic function, the efficacy and potency of various biogenic amines were compared with those of noradrenaline, isoprenaline, and β3-AR agonists 4-(-{[2-hydroxy-(3-chlorophenyl)ethyl]-amino}propyl)phenoxyacetate (BRL 37,344) and (R,R)-5-(2-{[2-(3-chlorophenyl)-2-hydroxyethyl]-amino}propyl)-1,3-benzo-dioxole-2,2-dicarboxylate (CL 316,243) by testing their lipolytic action in white fat cells. Five mammalian species were studied: rat, hamster and dog, in which selective β3-AR agonists act as full lipolytic agents, and guinea-pigs and humans, in which β3-AR agonists are less potent activators of lipolysis.
Several biogenic amines were inefficient (e.g. dopamine, tyramine and β-phenylethylamine) while others (synephrine, phenylethanolamine, epinine) were partially active in stimulating lipolysis in all species studied. Their actions were inhibited by all the β-AR antagonists tested, including those selective for β1- or β2-ARs. Octopamine was the only amine fully stimulating lipolysis in rat, hamster and dog fat cells, while inefficient in guinea-pig or human fat cells, like the β3-AR agonists. In rat white fat cells, β-AR antagonists inhibited the lipolytic effect of octopamine with a relative order of potency very similar to that observed against CL 316,243. Competitive antagonism of octopamine effect resulted in the following apparent pA
2 [–log(IC50), where IC50 is the antagonist concentration eliciting half-maximal inhibition] values: 7.77 (bupranolol), 6.48 [3-(2-ethylphenoxy)-1[(1 S)-1,2,3,4-tetrahydronaphth-1-ylaminol]-(2S)2-propanol oxalate, SR 59230A, a β3-selective antagonist], 6.30 [erythro-d,l-1(7-lethylindan-4-yloxy)-3-isopropylamino-butan-2-ol, ICI 118,551, a β2-selective antagonist] and 4.71 [(±)-[2-(3-carbomyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imi-dazolyl)-phenoxy]2-propanolmethane sulphonate, CGP 20712A, a β1-selective antagonist]. Octopamine had other properties in common with β3-AR agonists: stimulation of oxygen consumption in rat brown fat cells and very low affinity in displacing [3H]CGP 12,177 binding to β1- or β2-ARs in dog and rat adipocyte membranes. In Chinese hamster ovary (CHO) cells expressing human β3-ARs, octopamine inhibited [125I]ICYP binding with only twofold less affinity than noradrenaline while it exhibited an affinity around 200-fold lower than noradrenaline in CHO cells expressing human β1- or β2-ARs. These data suggest that, among the biogenic amines metabolically related to catecholamines, octopamine can be considered as the most selective for β3-ARs.
Hormone-sensitive lipase and cholesterol ester hydrolase of chicken adipose tissue were markedly activated by adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase (on the average, 235 to 275%; occasionally as much as 1000%). Diglyceride and monoglyceride hydrolases were also activated, but to a lesser extent (60 to 87%). The activation of all four hydrolases was inhibited by protein kinase inhibitor and reversed by the addition of exogenous protein kinase. Following activation by cAMP-dependent protein kinase, all four hydrolases were deactivated in a Mg2+-dependent reaction and then reactivated to or near initial levels on incubation with cAMP and Mg2+-ATP. The reversible deactivation is assumed to reflect activity of one or more protein phosphatases. The maximum activation obtainable for the four hydrolases decreased when the tissue had been previously exposed to glucagon, indicating that the glucagon-induced activation was probably similar to or identical with the activation demonstrated in cell-free preparations. The pH optima for the four hydrolase activities were similar (7.13 to 7.38). Although the absolute activities and relative degrees of kinase activation differed according to the particular emulsified substrates used, the results do not rule out the possibility that all four hydrolase activities are referable to a single hormone-sensitive hydrolase. Hormone-sensitive acyl hydrolases were separated from lipoprotein lipase by heparin-Sepharose affinity chromatography. Lipoprotein lipase was active against triolein, diolein, and monoolein, but not cholesterol oleate. Incubation of lipoprotein lipase with exogenous protein kinase, cAMP, and Mg2+ATP had no effect on any of the three hydrolase activities. Lipoprotein lipase was further purified to homogeneity and used to prepare antiserum in rabbits. The immunoglobin G fraction from these antisera completely inhibited lipoprotein lipase eluted from heparin-Sepharose columns. However, the hormone-sensitive hydrolase activities (not retained on heparin-Sepharose affinity chromatography) were not inhibited by anti-lipoprotein lipase immunoglobin G, and anti-lopoprotein lipase immunoglobin G did not affect the activation process in crude fractions. Thus, hormone-sensitive lipase and lipoprotein lipase, functionally distinct enzymes, have been physically resolved and immunochemically distinguished. Apparently lipoprotein lipase activity is not regulated, at least directly, by cAMP-dependent protein kinase.
Hormone-sensitive lipase activity (HSL), which is found in the supernatant of centrifuged homogenates of lipolytically quiet isolated rat adipocytes, was greatly reduced in or absent from the supernatant of lipolytically stimulated cells. The lipase was purified 100- to 250-fold from the supernatant of lipolytically quiet cells to 10-20% purity by a single passage over phenyl-Sepharose resin with high (greater than 70%) activity yields. Western blotting of adipocyte homogenate fractions with polyclonal antiserum raised against HSL showed that the enzyme shifted quantitatively from the supernatant of control cells to the floating "fat cake" of lipolytically stimulated cells. A similar shift to the fat cake was observed when cells were disrupted by hypotonic lysis and centrifugation rather than by homogenization. We propose that upon lipolytic activation of adipocytes and phosphorylation of HSL by cAMP-dependent protein kinase, the critical event is not an increase in catalytic activity (i.e., turnover number) but a translocation of the lipase to its substrate at the surface of the lipid storage droplet.
The basic protein protamine strongly inhibited hydrolysis of triolein emulsified with soybean phosphatidylcholine (PC) by pancreatic and carboxylester lipases; 10 micrograms/ml protamine, about 1000 times lower than the concentration of bovine serum albumin for the same effect, inhibited triolein hydrolysis completely. This inhibition was not affected by the incubation pH or bile salt concentration. Two other basic proteins, histone and purothionin, also inhibited hydrolysis of triolein emulsified with soybean PC, but they did not inhibit triolein hydrolysis by gastric lipase. When gum arabic was used as an emulsifier instead of soybean PC, these basic proteins did not affect triolein hydrolysis by pancreatic or carboxylester lipases. The effects of protamine on triolein hydrolysis by pancreatic and carboxylester lipases was studied using various phospholipids as emulsifiers. Protamine (10 micrograms/ml) did not inhibit hydrolysis of triolein emulsified with dicaproyl PC (DCPC), phosphatidic acid (PA), or phosphatidylserine (PS) by pancreatic and carboxylester lipases. Conversely, protamine at high concentrations slightly stimulated hydrolysis of triolein emulsified with DCPC or PA. Hydrolysis of triolein-phosphatidylethanolamine (PE) emulsion was inhibited slightly by protamine. The profiles of protamine inhibition of triolein-phosphatidyl-N,N-dimethyl ethanolamine (PDME) and triolein-phosphatidyl-N-monomethyl ethanolamine (PMME) emulsions were intermediate between those of PC and PE emulsions. These results suggest that the phospholipid species, especially choline moieties and fatty acid chain length, affect the lipase inhibitory activity of protamine profoundly. In vivo, oral administration of protamine to rats reduced and delayed the peak plasma triacylglycerol concentration, but neither bovine serum albumin nor an amino acid mixture with an amino acid composition identical to protamine affected plasma triacylglycerol levels.
Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h. These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.
—Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120–127.
Phospholipase C (α toxin of Clostridium perfringens) has been found to cause, at relative high concentrations, the lysis of fat cells isolated from rat epididymal adipose tissue.
Lysis of the fat cells resulted in the loss of insulin response in proportion to the amount of cells broken. It is suggested
that the effects of insulin on glucose metabolism by the fat cell are dependent on the presence of an intact cell membrane.
The level of flexokinase activity in the fat cell was not affected by insulin or phospholipase C; sufficient hexokinase was
present to account for all the glucose phosphorylated by fat cells in response to insulin.
Evidence is presented that glucose is transported in the fat cell by a carrier-mediated, stereospecific process. Insulin and
treatment of fat cells with phospholipase C under conditions that did not cause lysis, stimulated the transport of glucose.
Anabolic processes, such as fatty acid synthesis from glucose and amino acid incorporation into protein, were also stimulated
by insulin and phospholipase C. The action of phospholipase C on glucose transport and amino acid utilization was a function
of enzyme concentration, suggesting that the amount of cellular phospholipid hydrolyzed by the enzyme determined the amount
of solute entering the cell. Phospholipids appear, therefore, to be linked to transport processes.
The common effects of insulin and phospholipase C on the fat cell suggests that the same parameter in the cell is affected
by these substances. It is hypothesized that insulin and phospholipase C act on the plasma membrane to alter the configuration
of its lipoproteins from a laminated to a micellar or globular form. The latter configuration of the membrane lipoproteins
might have interstices that permit the carrier-mediated passage of solutes into the cell.
Several monoclonal antibodies (mAbs) were prepared against human pancreatic lipase (HPL). Two enzyme-linked immunosorbent
assay (ELISA) procedures were set up for screening hybridomas producing specific antibodies. Four mAbs (81-23, 146-40, 315-25,
and 320-24) of the IgG1 isotype were found to react with HPL in both simple sandwich and double sandwich ELISAs, while mAb
248-31, of the IgG2b isotype, reacted only with HPL in a double sandwich ELISA. The results of Western blot analysis carried
out with native and SDS-denatured HPLs indicated that mAb 248-31 recognized only native HPL, while all the other mAbs recognized
both forms of HPL. Since mAb 248-31 did not recognize SDS-denatured HPL, it was not possible to localize its epitope. To carry
out epitope mapping along the primary sequence of HPL, four fragments (14, 26, 30, and 36 kDa) resulting from a limited chymotryptic
cleavage of HPL were characterized by Western blotting as well as N-terminal amino acid sequence analysis.
Of the above five anti-HPL mAbs, four (81-23, 248-31, 315-25, and 320-24) were found to inhibit the lipolytic activity of
HPL (in both the presence and absence of bile salts and colipase), while mAb 146-40 had no inhibitory effects. The epitope
recognized by mAb 146-40 was found to be located in the N-terminal domain (Lys1-Phe). Combined immunoinactivation and epitope mapping studies showed that three inhibitory mAbs (81-23, 315-25, and 320-24) recognize
overlapping epitopes from the hinge region between the N- and C-terminal domains of HPL, belonging to the 26-kDa fragment.
In the presence of lipids, a significant decrease has been observed in the bending angle between the N- and C-terminal domains
of the HPL tertiary structure (van Tilbeurgh, H., Egloff, M. P., Martinez, C., Rugani, N., Verger, R. and Cambillau, C.(1993)
Nature 362, 814-820). From the present immunochemical data, we further propose that locking the hinge movement with mAbs may induce
lipase immunoinactivation.
Following the feeding of a triacylglycerol-rich meal to healthy adult human beings, duodenal contents were aspirated for ex vivo chemical and physical-chemical analyses. The aspirates were collected during established lipid digestion and absorption into a "cocktail" of chemical inhibitors that rapidly inhibited ex vivo lipolysis. Following ultracentrifugation, the lipids separated into a floating oil layer, several interfacial layers, a "clear" or turbid "subphase", and a precipitated "pellet". By chemical and phase analyses, the floating layer was composed of oil-in-water emulsion particles with cores of triacylglycerol (TG), diacylglycerols (DG), and cholesteryl esters (CE) emulsified with a surface coat of partially ionized fatty acids (FA), monoacylglycerols (MG), diacylphosphatidylcholine (PL), and bile salts (BS). The interfacial layers contained similar emulsion particles dispersed among excess emulsifier which adopted a lamellar liquid-crystalline structure. Precipitated pellets were composed principally of emulsifying lipids, with smaller amounts of crystalline calcium soaps and BS. Relative lipid compositions of all but three subphases fell within a two-phase region of the condensed ternary phase diagram (Staggers et al., 1990, companion paper) where saturated mixed micelles composed of BS, FA "acid-soaps", MG, PL, cholesterol (Ch), and traces of DG (and TG) coexisted with unilamellar liquid-crystalline vesicles composed of the same lipids. Attempts to achieve clean separation of vesicles from micelles by repeat ultracentrifugation failed. Compared with the structure and sizes of lipid particles in equilibrated model systems (Staggers et al., 1990), quasielastic light scattering (QLS) analysis revealed that ex vivo micellar sizes (mean hydrodynamic radii, Rh) were similar (less than or equal to 40 A), whereas unilamellar vesicle sizes (Rh = 200-600 A) were appreciably smaller. Two-component QLS analysis of the subphases showed that much larger proportions of lipids were solubilized by micelles than were dispersed as unilamellar vesicles. When followed as functions of time, vesicles frequently dissolved spontaneously into mixed micelles, indicating that, in the nonequilibrium in vivo conditions, the constituent micellar phase was often unsaturated with lipids. These results are consistent with the hypothesis that, during hydrolysis of emulsified DG and TG by luminal lipases, unilamellar vesicles originate in lamellar liquid crystals that form at emulsion-water interfaces in the upper small intestine. In a BS-replete environment, unilamellar vesicles probably represent the primary dispersed product phase of human fat digestion and facilitate the dissolution of lipolytic products into unsaturated mixed micelles.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of capsaicin, a pungent principle of hot red pepper, were studied in experiments using male rats fed a diet containing 30% lard. Capsaicin was supplemented at 0.014% of the diet. The level of serum triglyceride was lower when capsaicin was present in the diet than when it was not. Levels of serum cholesterol and pre-beta-lipoprotein were not affected by the supplementation of capsaicin. The perirenal adipose tissue weight was lower when capsaicin was present in the diet than when it was not. Hepatic enzyme activities of glucose-6-phosphate dehydrogenase and adipose lipoprotein lipase were lower in rats fed the 30% lard diet than in those fed a nonpurified diet. Activities of these two enzymes were higher when capsaicin was added to the diet than when it was not. Hepatic acetyl-CoA carboxylase, beta-hydroxyacyl-CoA dehydrogenase, and adipose hormone-sensitive lipase activities were not affected by capsaicin feeding. Lipid absorption was not affected by the supplementation of capsaicin. The perirenal adipose tissue weight and serum triglyceride were decreased as the level of capsaicin in the diet increased up to 0.021%. These results suggest that capsaicin stimulates lipid mobilization from adipose tissue and lowers the perirenal adipose tissue weight and serum triglyceride concentration in lard-fed rats.
The mode of action of capsaicin on energy metabolism was investigated in rats. The oxygen consumption was higher when capsaicin (6.0 mg/kg) was intraperitoneally injected than when it was not injected. The respiratory quotient (R.Q.) increased and then decreased after the administration of capsaicin. The levels of serum glucose and immunoreactive insulin rapidly increased after the administration of capsaicin. Also, liver glycogen rapidly decreased, in contrast to the serum glucose concentration which rapidly increased. The serum-free fatty acid level gradually increased after the administration of capsaicin. These alterations in energy metabolism on the administration of capsaicin were similar to those in the metabolism of epinephrine, and were specifically inhibited by various beta-adrenergic blockers. On the other hand, the alterations were not affected by pretreatment with alpha-adrenergic or ganglion blockers. These results suggest that the mode of action of capsaicin on the enhancement of energy metabolism in rats comprises a direct (as an agonist) and/or an indirect (via catecholamine) beta-adrenergic action. Therefore, it was speculated that the adrenergic action of capsaicin resulted, at least in part, in a decrease in the perirenal adipose tissue weight and serum triglyceride concentration in rats fed a high fat diet supplemented with capsaicin (T. Kawada et al., J Nutr 116:1272-1278, 1986).
1. In order to examine the interaction of dietary fat and carbohydrate in the regulation of lipid metabolism, we have studied hepatic and extrahepatic lipogenesis, and adipose tissue lipoprotein lipase ( EC 3.1.1.34) in rats fed on one of the following diets: a fructose-based diet containing 0 (F0) or 150 g maize oil (F15)/kg, or a glucose based diet containing 0 (G0) or 150 g maize oil (G15)/kg.
2. The rats were meal-fed on the diets for 2 weeks after which the activities of a number of hepatic ‘lipogenic’ enzymes were measured and the activity of epididymal-fat-pad lipoprotein lipase. The activities of the lipogenic enzymes were: F0 > G0 > G15 > F15. Lipoprotein lipase activity was F0 = G0 = F15 = G15. The percentage of total body fatty acid synthesis which occurred in the liver was F0 > G0 > F15 > G15.
3. We conclude that fructose-induced hypertriglyceridaemia is primarily a result of the increased hepatic synthesis rather than decreased adipose-tissue lipoprotein lipase activity.
Hormone-sensitive lipase, a key enzyme in fatty acid mobilization, overall energy homeostasis, and possibly steroidogenesis, is acutely controlled through reversible phosphorylation by catecholamines and insulin. The 757-amino acid sequence predicted from a cloned rat adipocyte complementary DNA showed no homology with any other known lipase or protein. The activity-controlling phosphorylation site was localized to Ser563 in a markedly hydrophilic domain, and a lipid-binding consensus site was tentatively identified. One or several messenger RNA species (3.3, 3.5, or 3.9 kilobases) were expressed in adipose and steroidogenic tissues and heart and skeletal muscle. The human hormone-sensitive lipase gene mapped to chromosome 19 cent-q13.3.
This chapter presents enzymatic methods for quantification of lipoprotein lipids. The methods described are primarily developed for cholesterol measurement in human plasma and lipoprotein fractions and are well suited for high-volume screening applications. Two reagents are described, one a commercial kit method 14 (Boehringer-Mannheim High Performance) and one prepared in-house from the constituents (modified Centers for Disease Control (CDC)). For both reagents an application for the ABA 200 chemical analyzer and a manual procedure are given. Enzymatic methods have significant advantages. Among these are improved specificity, which permits in many cases direct measurement of the analyte without pretreatment, i.e., hydrolysis or extraction. Although the direct enzymatic methods are not totally free from interference effects, with reasonable precautions they can give acceptable results for most specimens. The enzymatic methods are usually more sensitive, permit measurement in small specimen volumes, and are versatile with a variety of different color reactions. The reagents are generally mild and well suited to modern chemical analyzers.
Using an improved method of gel electrophoresis, many hitherto unknown
proteins have been found in bacteriophage T4 and some of these have been
identified with specific gene products. Four major components of the
head are cleaved during the process of assembly, apparently after the
precursor proteins have assembled into some large intermediate
structure.
1. The metabolism of 4-(4-hydroxyphenyl)butan-2-one(raspberry ketone) was studied in rats, guinea-pigs and rabbits. 2. Following intragastric dosage (1 mmol/kg) urinary metabolite excretion was nearly complete within 24 h, amounting to roughly 90% of the dose in all species. 3. The most prominent urinary metabolites were raspberry ketone and its corresponding carbinol, both largely conjugated with glucuronic acid and/or sulphate. The extent of ketone reduction was greatest in rabbits. 4. Oxidative metabolism included ring hydroxylation and side-chain oxidation. The latter pathway led to 1,2- and 2,3-diol derivatives. It is proposed that the latter undergo cleavage to furnish the C6-C3 and C6-C2 derivatives detected.
To assess the relationship among the structure, pungency and thermogenic action, a series of capsaicin analogs with saturated acyl moieties (heptanoyl to eicosanoyl vanillylamide) were synthesized. Pungency of the compounds and the thermogenic action, which was examined by the potential of the compounds (655 nmol/kg, i.v.) to enhance adrenal catecholamine secretion for 15 min in anesthetized rats, were compared. On the chain length of the acyl moieties of the analogs, nonanoyl to octadecanoyl vanillylamide caused strong adrenal catecholamine secretion, but heptanoyl vanillylamide and eicosanoyl vanillylamide caused weak or no response. Pungent analogs except heptanoyl vanillylamide and non-pungent analogs except eicosanoyl vanillylamide had strong potency to secrete adrenal catecholamine.
Chitin and chitosan are polymers containing more than 5000 acetylglucosamine and glucosamine units, respectively, and their molecular weights are over one million Daltons. The present study assessed the effects of chitin-chitosan on the activity of pancreatic lipase in vitro and on the degree of fat storage induced in mice by the oral administration of a high-fat diet for nine weeks.
Mice were fed a high-fat diet and treated with chitin-chitosan for nine weeks. Experiments were also carried out to clarify whether or not chitin-chitosan inhibited pancreatic lipase activity in assay systems using triolein emulsified with lecithin, gum arabic or Triton X-100.
Chitin-chitosan prevented the increase of body weight, hyperlipidaemia and fatty liver induced by a high-fat diet. Chitin-chitosan inhibited hydrolysis of triolein, emulsified with phosphatidylcholine, but not that of triolein emulsified with gum arabic and Triton X-100. These results suggest that the site of inhibitory action of chitin-chitosan may not be the enzyme but its substrate.
The anti-obesity effects of chitin-chitosan in high-fat diet-treated mice might be partly due to the inhibition of intestinal absorption of dietary fat. Consequently, chitin-chitosan might cause improvement of the fatty liver and hyperlipidaemia in mice fed a high fat diet through inhibiting intestinal absorption of dietary fat.
Oolong tea is traditionally reported to have anti-obesity and hypolipidaemic effects. The present study was performed to clarify whether oolong tea prevented obesity induced in mice by the oral administration of a high-fat diet for 10 weeks.
High-fat diet-induced obese mice were treated with oolong tea for 10 weeks. The effects of various active fractions isolated from oolong tea on noradrenaline-induced lipolysis were examined with isolated fat cells and a cell-free system consisting of lipid droplets and hormone-sensitive lipase (HSL).
The mean food consumption was not significantly different between high-fat diet-treated mice and high-fat plus oolong tea diet-treated mice. Oolong tea prevented the obesity and fatty liver induced by a high-fat diet. A water extract of oolong tea enhanced noradrenaline-induced lipolysis, and the active substance was identified as caffeine. Caffeine enhanced noradrenaline-induced lipolysis in fat cells without a concomitant increase in HSL activity and also accelerated the hormone-induced lipolysis in a cell-free system consisting of lipid droplets and HSL, but not in the cell-free system with sonicated lipid droplets and HSL. Oolong tea extract inhibited pancreatic lipase activity.
It was demonstrated that the anti-obesity effects of oolong tea in high-fat diet-treated mice might be due partly to the enhancing effect of caffeine isolated from oolong tea on noradrenaline-induced lipolysis in adipose tissue, and to the inhibitory action of some other substance in oolong tea on pancreatic lipase activity. Caffeine was found to enhance lipolysis through acting on lipid droplets but not on HSL. The results suggest that oolong tea may be an effective crude drug for the treatment of obesity and fatty liver caused by a high-fat diet.
An assay for total hormone-sensitive lipase (HSL) in rat fat cells was devised in which fat-associated HSL was solubilized
with ether, and triolein or cholesteryloleate was used as substrate. Norepinephrine (NE) caused marked release of glycerol
from fat cells but did not activate HSL as estimated using triolein or cholesteryloleate as substrate. Propranolol, a β-blocker,
inhibited NE-induced lipolysis in fat cells without a concomitant reduction in HSL activity. The antilipolytic action of insulin
on NE-induced lipolysis could not be explained by a decrease in HSL activity. Neither ACTH-induced lipolysis in fat cells
nor its inhibition by insulin was accompanied by matching fluctuations in HSL activity. These results indicate that neither
NE and ACTH-induced lipolysis in fat cells, nor the antilipolytic actions of propranolol and insulin, involve fluctuations
in HSL activity
Quality characteristics of raspberries and blackberries
- Ravai
Ravai, M., 1996. Quality characteristics of raspberries and blackberries. Cereal Foods World 41, 773-775.
Adipose tissue lipase
- P Belfrage
- G Fredrikson
- P Str3lfors
- H Torquist
Belfrage, P., Fredrikson, G., Str3lfors, P., Torquist, H., 1984. Adipose tissue lipase. In: Borgströ, B., Brockman, H.L. (Eds.), Lipase. Elsevier, Amsterdam, pp. 365 – 416.
Hormone-sensitive lipase: sequence, expression
- C Holm
- T G Kirchgessner
- K L Svenson
- G Fredrikson
- S Nilsson
- C G Miller
- J E Shively
- C Heinzmann
- R S Sparkes
- T Mohandas
- A J Lusis
- P Belfrage
- M C Schotz
Holm, C., Kirchgessner, T.G., Svenson, K.L., Fredrikson, G., Nilsson, S., Miller, C.G., Shively, J.E., Heinzmann, C., Sparkes, R.S., Mohandas, T., Lusis, A.J., Belfrage, P., Schotz, M.C., 1988. Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-p13.
Adipose tissue lipase
- Belfrage