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Pomegranate vinegar beverage reduces visceral fat accumulation in association with AMPK activation in overweight women: A double-blind, randomized, and placebo-controlled trial

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... Limited studies, however, have evaluated the effect of pomegranate consumption on weight in humans, with mixed results. Although some trials have shown that pomegranate has a weight reduction effect (González-Ortiz, Martínez-Abundis, Espinel-Bermúdez, & Pérez-Rubio, 2011), other studies found no significant effect (Ekhlasi, Shidfar, Agah, Merat, & Hosseini, 2016;Park et al., 2014;Sohrab et al., 2014;Tsang, Smail, Almoosawi, Davidson, & Al-Dujaili, 2012). ...
... The main characteristics of 13 eligible trials are summarized in Table 2. Kojadinovic et al., 2016;Lynn et al., 2012;Manthou et al., 2017;Sadegh Eghbali et al., 2016;Sohrab et al., 2014;Sumner et al., 2005); pomegranate extracts (PE), which used in three studies (Hosseini et al., 2016;Stockton et al., 2017;Wu et al., 2015); and pomegranate vinegar (PV), which was used in one study (Park et al., 2014). All studies except one study (Sohrab et al., 2014) did not consider energy adjustment of dietary intake and only supplemented pomegranate in addition to diet in participants. ...
... The details of the risk of bias assessment of individual studies are presented in Table 3. Only 4 of 13 included studies explained how the subjects were randomized, such as internet random number generator website (Stockton et al., 2017), block randomization (Hosseini et al., 2016;Lynn et al., 2012), and computer generated random numbers (Park et al., 2014), whereas other trials did not mention randomization Although there was no significant heterogeneity between studies (Q statistic = 14.42, I 2 = 30.6%, ...
Article
Pomegranate is rich in tannins, polyphenols, flavonoids, and several other types of antioxidant compounds whose role in weight loss has been shown in previous studies. However, the results have been mixed regarding the effects of pomegranate consumption on weight loss. Electronic databases such as PubMed, Scopus, ISI Web of Science, and Google Scholar were systematically searched up to May 2018 for controlled clinical trials assessing the effect of pomegranate consumption on weight loss. A random effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI) as the difference between the mean for the intervention and control groups. Thirteen randomized controlled trials (including 513 participants) were included in the present meta‐analysis. Compared with the control groups, there was no significant reduction in bodyweight, body mass index, waist circumference, and body fat percentage after pomegranate consumption (WMD = −0.23 kg, 95% CI: −0.94, 0.47, P = 0.515; WMD = −0.12 kg/m², 95% CI: −0.29, 0.03, P = 0.132; WMD = −0.08 cm, 95% CI: −0.33, 0.17, P = 0.534; WMD = −0.05, 95% CI: −1.66, 1.55, P = 0.947, respectively). According to the results of the present systematic review and meta‐analysis, there was no significant effect of pomegranate consumption on weight and body composition indices.
... From the 20 studies selected and included in this systematic review, seven were from Iran [10,12,[65][66][67][68][69], four were from the United States [70][71][72][73], three were from the United Kingdom [74][75][76], one was from Mexico [77], one was from Spain [78], one was from Greece [79], one was from Serbia [80], one was from Israel [81], and one was from South Korea [82]. In the included studies, the respective authors used different formulations derived from pomegranate to treat the participants: pomegranate juice [10,12,65,68,69,[71][72][73][75][76][77][78][79][80][81], pomegranate extract [68,70,73,74], pomegranate juice enriched with probiotic microorganisms [67], diluted pomegranate juice [66,78], and pomegranate vinegar [82]. The studies did not report serious adverse effects and high drop-outs rates. ...
... Of these, 147 studies met the eligibility criteria and, after applying the inclusion and exclusion criteria, only 20 were included in the qualitative analysis. From the 20 studies selected and included in this systematic review, seven were from Iran [10,12,[65][66][67][68][69], four were from the United States [70][71][72][73], three were from the United Kingdom [74][75][76], one was from Mexico [77], one was from Spain [78], one was from Greece [79], one was from Serbia [80], one was from Israel [81], and one was from South Korea [82]. In the included studies, the respective authors used different formulations derived from pomegranate to treat the participants: pomegranate juice [10,12,65,68,69,[71][72][73][75][76][77][78][79][80][81], pomegranate extract [68,70,73,74], pomegranate juice enriched with probiotic microorganisms [67], diluted pomegranate juice [66,78], and pomegranate vinegar [82]. ...
... From the 20 studies selected and included in this systematic review, seven were from Iran [10,12,[65][66][67][68][69], four were from the United States [70][71][72][73], three were from the United Kingdom [74][75][76], one was from Mexico [77], one was from Spain [78], one was from Greece [79], one was from Serbia [80], one was from Israel [81], and one was from South Korea [82]. In the included studies, the respective authors used different formulations derived from pomegranate to treat the participants: pomegranate juice [10,12,65,68,69,[71][72][73][75][76][77][78][79][80][81], pomegranate extract [68,70,73,74], pomegranate juice enriched with probiotic microorganisms [67], diluted pomegranate juice [66,78], and pomegranate vinegar [82]. The studies did not report serious adverse effects and high dropouts rates. ...
Article
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Pomegranate (Punica granatum L.) can be considered a multipurpose medicinal and dietary plant due to its anti-inflammatory and antioxidant actions. Pomegranate can be used to prevent or treat metabolic syndrome (MetS) risk factors. Although previously published reviews addressed the effects of pomegranate on different diseases, there is no systematic review that exclusively focuses on clinical trials related to all MetS-related risk factors. In view of this limitation, the objective of this up to-date, comprehensive, and systematic review is to critically evaluate the potential of pomegranate (P. granatum) on various MetS risk factors on the basis of clinical studies. PubMed, EMBASE, MEDLINE, Google Scholar, COCHRANE, and Clinical Trials.gov databases were searched on 15 October 2021. The Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were followed, and the bias risk evaluation was performed according to the Cochrane Handbook for Systematic Reviews of Interventions. We identified 5683 studies in the databases. After removing the duplicates, 3418 studies remained. Of these, 147 studies met the eligibility criteria, and finally, only 20 were included in the qualitative analysis. The included studies suggest that pomegranate can be beneficial to reduce body weight, blood pressure, glycemia, triglycerides, total cholesterol, and low-density lipoprotein cholesterol. Moreover, it can augment high density lipoprotein cholesterol levels and improve insulin resistance. Although relevant effects were observed, additional well designed clinical trials are needed to determine the correct formulations and doses to be used to prevent or treat MetS components.
... From these, 16 studies involving 910 participants comprehensively met inclusion criteria and were included. [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] From the 60 excluded studies, the most common reasons for exclusion were investigation of wrong intervention or route of administration (ie, delivery of pure acetic acid in the absence of a food/ fluid matrix through intravenous injections or pill ingestion) (n ¼ 23) and postprandial data being solely analyzed after the intervention (n ¼ 15). All 16 included studies were eligible for quantitative assessment via meta-analysis. ...
... The habitual dietary intake of participants at baseline was assessed in 12 studies. [40][41][42][43][44][45]48,49,51,[53][54][55] Intervention adherence measurements and collection of dietary intake data during the intervention periods were assessed in nine trials. [42][43][44][45]48,49,51,53,55 A run-in period was included in five studies, lasting either 1, 51 2, 42,48,52 or 3 weeks. ...
... [40][41][42][43][44][45]48,49,51,[53][54][55] Intervention adherence measurements and collection of dietary intake data during the intervention periods were assessed in nine trials. [42][43][44][45]48,49,51,53,55 A run-in period was included in five studies, lasting either 1, 51 2, 42,48,52 or 3 weeks. 49 All data obtained for quantitative analysis included end of intervention values, with the exception of one study 46 for which the final reported time point (6 weeks) was used. ...
Article
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Background Acetic acid is a short-chain fatty acid that has demonstrated biomedical potential as a dietary therapeutic agent for the management of chronic and metabolic illness comorbidities. In human beings, its consumption may improve glucose regulation and insulin sensitivity in individuals with cardiometabolic conditions and type 2 diabetes mellitus. Published clinical trial evidence evaluating its sustained supplementation effects on metabolic outcomes is inconsistent. Objective This systematic review and meta-analysis summarized available evidence on potential therapeutic effects of dietary acetic acid supplementation via consumption of acetic acid–rich beverages and food sources on metabolic and anthropometric outcomes. Methods A systematic search was conducted in Medline, Scopus, EMBASE, CINAHL Plus, and Web of Science from database inception until October 2020. Randomized controlled trials conducted in adults evaluating the effect of dietary acetic acid supplementation for a minimum of 1 week were included. Meta-analyses were performed using a random-effects model on fasting blood glucose (FBG), triacylglycerol (TAG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), glycated hemoglobin (HbA1c), body mass index (BMI), and body fat percentage. Statistical heterogeneity was assessed by calculation of Q and I² statistics, and publication bias was assessed by calculation of Egger’s regression asymmetry and Begg’s test. Results Sixteen studies were included, involving 910 participants who consumed between 750 and 3600 mg acetic acid daily in interventions lasting an average of 8 weeks. Dietary acetic acid supplementation resulted in significant reductions in TAG concentrations in overweight and obese but otherwise healthy individuals (mean difference [MD] = −20.51 mg/dL [95% confidence intervals = −32.98, −8.04], P = .001) and people with type 2 diabetes (MD = −7.37 mg/dL [−10.15, −4.59], P < .001). Additionally, acetic acid supplementation significantly reduced FBG levels (MD = −35.73 mg/dL [−63.79, −7.67], P = .01) in subjects with type 2 diabetes compared with placebo and low-dose comparators. No other changes were seen for other metabolic or anthropometric outcomes assessed. Five of the 16 studies did not specify the dose of acetic acid delivered, and no studies measured blood acetate concentrations. Only one study controlled for background acetic acid-rich food consumption during intervention periods. Most studies had an unclear or high risk of bias. Conclusion Supplementation with dietary acetic acid is well tolerated, has no adverse side effects, and has clinical potential to reduce plasma TAG and FBG concentrations in individuals with type 2 diabetes, and to reduce TAG levels in people who are overweight or obese. No significant effects of dietary acetic acid consumption were seen on HbA1c, HDL, or anthropometric markers. High-quality, longer-term studies in larger cohorts are required to confirm whether dietary acetic acid can act as an adjuvant therapeutic agent in metabolic comorbidities management.
... Besides the rice vinegar, the vinegar of other raw materials are also featured in functional properties, such as sherry wine vinegar with different fruits (orange, strawberry, grape and lemon) (Bastante et al., 2010); apple vinegar, with potential in the prevention of tumors (Abe et al., 2007), in lowering cholesterol and triglycerides level (Budak et al., 2011); vinegar made from ginseng extracts with antiglycemic and antidiabetic effect (Lim et al., 2009); pomegranate vinegar, being classified as a functional condiment due to phenolic compounds and antioxidant activity with potential in reducing the accumulation of visceral fat (Ordoudi et al., 2014;Park et al., 2014). In Indian jujube vinegar (Zizyphus mauritiana) -a little exploited Indian fruit -the authors found a high antioxidant activity of the fermented, and it may be defined as a functional vinegar (Vithlani & Patel, 2010); and, in general, Salbe et al. (2009) assessed the effects of vinegar on the regulation of human glucose and possible mechanisms of action. ...
... The study was conducted with pomegranate vinegar, on 78 overweight women, who were randomly assigned to receive either pomegranate vinegar (1.5 g acetic acid per day) or placebo, for 8 weeks. Vinegar decreases visceral adipose tissue (measured by computerized tomography), causing increased phosphorylation of AMPK in comparison with the placebo group (Park et al., 2014). ...
Article
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Resumo Vinegar is a widely used condiment, consumed by all social classes and has great potential for health bene­fits, which justifies the concern for their beneficial activity. The country is still a beginner in vinegar research, concerning the verification of its health benefits, as the raw materials used and the production process. The article aims to gather and discuss studies that show the vinegar beneficial effects for human health. In stud­ies conducted in Europe and Asia, it was observed that consumption of vinegar can be beneficial, as it showed antitumor effect, reduced the blood glucose level, effects on the immune system, anti-hypertensive effect, among others. Those responsible for the medicinal effects are acetic acid (at least 4% in vinegars, under Brazilian law), but also other compounds resulting from the metabolism of microorganisms during the stages of fermentation and/or aging. Despite these results, “in vivo” research as are still deficient concerning the recommended daily doses that prove the medicinal efficacy of vinegar are unknown. However, in view of the favorable results, the functional potential of these vinegars should not be ignored, then, more studies are necessary in order to demonstrate their functional properties. Additional keywords: antioxidant action; human health benefits; vinegar consumption.
... It suppressed lipid accumulation in 3T3-L1 cells and inhibited adipogenic differentiation, which involves reducing fat accumulation mass and hepatic steatosis [93]. The molecular mechanism involved in the control of body fat by pomegranate vinegar was evoked for the first time by [94] who proved that the pomegranate vinegar activated AMPK in adipose tissue. The activation of AMPK inhibits anabolic pathways through suppression of SERBP-1c ( Figure 1) [18,19,94]. ...
... The molecular mechanism involved in the control of body fat by pomegranate vinegar was evoked for the first time by [94] who proved that the pomegranate vinegar activated AMPK in adipose tissue. The activation of AMPK inhibits anabolic pathways through suppression of SERBP-1c ( Figure 1) [18,19,94]. Acetic acid is the main component present in vinegar. ...
Article
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The popularity of fruits vinegar (FsV) has been increased recently as a healthy drink wealthy in bioactive compounds that provide several beneficial properties. This review was designed in the frame of valorization of fruits vinegar as a by-product with high value added by providing overall information on its biochemical constituents and beneficial potencies. It contains a cocktail of bioactive ingredients including polyphenolic acids, organic acids, tetramethylperazine, and melanoidins. Acetic acid is the most abundant organic acid and chlorogenic acid is the major phenol in apple vinegar. The administration of fruits vinegar could prevent diabetes, hypercholesterolemia, oxidative stress, cancer, and boost immunity as well as provide a remarkable antioxidant ability. The production techniques influence the quality of vinegar, and consequently, its health benefits.
... Intake of tomato vinegar on a daily basis can decrease the visceral fat completely along with epididymis adipocyte mass [74]. Vinegar extract from pomegranate appears to be more famous for obesity treatment because it has been reported to constrain lipogenesis and boost fatty acid beta-oxidation [75,76]. In addition to this, consumption of pomegranate vinegar may encourage the modulation of peroxisome proliferator-activated receptor alpha (PPARa) [65] and carnitine palmitoyl transferees 1 alpha (CPT-1a) mRNA expression comprising phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) more eff ectively than acetic acid [75], showing that PV is more powerful than acetic acid at decreasing obesity. ...
... AMPK phosphorylation will incite PPAR-alpha gene expression [79] that moderates mRNA expression of fatty acid oxidation enzymes such as CPT-1a and acetyl-CoA (ACCA) oxidase, which may boost fatty acid oxidation. Triggering of AMPK along with downregulation of SREBP-1c [76] and carbohydrate-responsive Vitamin (2017), 1-12 © 2017 Hogrefe rating Alzheimer's patients' symptoms [92]. Still, the exact mechanisms of these eff ects are undetermined, and the eff ects of vinegar on the brain are not known exactly, so that more research on this phenomenon is needed. ...
Article
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While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has foundthat vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates area good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current reviewpaper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseasesboth in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.
... These data are confirmatory and support many other previous similar studies in other cell lines and different cancer types. Indeed, EA inhibited cell proliferation and induced cell apoptosis in MOLT-4 leukaemia, KLE and AN3CA endometrial, HCT-15 colon, and MCF-7and GDC-0941 breast, TSGH8301 and T24 bladder, DU145 prostate, A2780 ovarian, and A549 lung cancer cell line.9,[22][23][24][25][26][29][30][31][32] Also, EA inhibited migration and invasion of Saos-2 and MG63 osteosarcoma, PC-3 and PLS10 prostate, and A2780 OC.32,33 ...
... Indeed, EA inhibited cell proliferation and induced cell apoptosis in MOLT-4 leukaemia, KLE and AN3CA endometrial, HCT-15 colon, and MCF-7and GDC-0941 breast, TSGH8301 and T24 bladder, DU145 prostate, A2780 ovarian, and A549 lung cancer cell line.9,[22][23][24][25][26][29][30][31][32] Also, EA inhibited migration and invasion of Saos-2 and MG63 osteosarcoma, PC-3 and PLS10 prostate, and A2780 OC.32,33 ...
Article
Full-text available
This study investigated the effect of Ellagic acid (EA) on SKOV‐3 cell growth and invasiveness and tested if the underlying mechanism involves modulating autophagy. Cells were treated with EA in the presence or absence of chloroquine (CQ), an autophagy inhibitor, compound C (CC), an AMPK inhibitor, or an insulin‐like growth factor‐1 (IGF‐1), a PI3K/Akt activator. EA, at an IC50 of 36.6 µM, inhibited cell proliferation, migration, and invasion and induced cell apoptosis in SKOV‐3 cells. These events were prevented by CQ. Also, EA increased levels of Beclin‐1, ATG‐5, LC3I/II, Bax, cleaved caspase‐3/8 and reduced those of p62 and Bcl‐2 in these cancer cells. Mechanistically, EA decreased levels of p‐S6K1 (Thr389) and 4EBP‐1 (Thr37/46), two downstream targets of mTORC1, and p‐Akt (Thr308) but increased levels of AMPK (Thr172) and p‐raptor (Ser792), a natural inhibitor of mTORC1. CC or IGF‐1 alone partially prevented the effect of EA on cell survival, cell invasions, and levels of LDH, Beclin‐1, and cleaved caspase‐3. In conclusion, EA can inhibit SKOV‐3 growth, migration, and invasion by activating cytotoxic autophagy mediated by inhibition of mTORC1 and Akt and activation of AMPK.
... The production of vinegar is controlled by recognized quality standards, and some of these products are considered to be culinary specialties that are used all over the world (e.g., Sherry Vinegar and Balsamic Vinegar of Modena), although most of these products are made from wine. In this regard, the use of pomegranate wine (PW) and pomegranate vinegar (PV) is still limited, 8,11,12 and considering the stable total polyphenol content 12 and potential health benefits, further research into the elaboration of these products is desirable. Gabsi is one of the best-known pomegranate cultivars in Tunisia, having an appreciable sensory quality and a high commercial value. ...
Article
Background: There is growing interest in the beneficial health effects of certain fruits, such as pomegranate, and their by-products, like vinegar. Vinegars contain antioxidant compounds such as polyphenols, which can scavenge free radicals in the body. In this study, the antioxidant properties (ABTS and DPPH scavenging capacities) and global polyphenolic composition of a new functional product, namely a pomegranate vinegar produced in the laboratory from the Gabsi variety, were evaluated and compared with those of commercial wine vinegars (Sherry and Rioja red wine Spanish vinegars). The evolution of the polyphenolic and volatile compositions during production of the pomegranate vinegar was also studied. Results: The results indicate that pomegranate contained a relatively stable total phenolic content that is suitable for the elaboration of vinegar and that this product had an antioxidant capacity comparable to, or even better than, that observed for aged wine vinegars. Regarding the volatiles profile, a high proportion of esters (close to 50%), in relation to alcohols and fatty acids, was observed for pomegranate vinegar and this is consistent with the high red fruits character identified by sensory analysis. Conclusion: Pomegranate vinegar produced in the laboratory has an antioxidant activity and a global phenolic content similar to those of red wine vinegars and higher than most of white the wine vinegars studied. The pomegranate vinegar retained the red fruit sensory character of pomegranate fruit.
... Vinegar is a popular food product manufactured in a two-stage fermentation process from a variety of raw materials, mostly including fruits. Many studies conducted so far have addressed fruit vinegar production via fermentation of juices from: apples, strawberries or pomegranates, and also from other untypical raw materials, like: Korean black raspberry or Litchi Chinensis fruit tree [1][2][3][4]. Ample investigations have demonstrated fruit vinegars to possess strong antioxidative properties and, thereby, to serve protective functions against adverse effects of pathogenic enteral flora, to exhibit anti-diabetic potential, to reduce blood concentration of lipids, to prevent arterial hypertension or to decrease the glycemic index of food products being sources of carbohydrates. Vinegars may as well be applied in the production of medicinal preparations being less straining to the body [5][6][7][8][9]. ...
Article
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We analyzed the effect of Cornelian cherry varieties differing in fruit color ('Yantaryi'-yellow fruits, 'Koralovyi'-coral fruits, 'Podolski'-red fruits) and the production method on the physicochemical and antioxidative properties of Cornelian cherry vinegars, and on their content of iridoids and polyphenols. Acetic fermentation was conducted by two methods: I) single-stage (spontaneous) acetic fermentation, without inoculation with microorganisms, and II) two-stage fermentation in which the first stage involved the use ofSaccharomyces bayanus-Safspirit fruit yeast for alcoholic fermentation, and the second one included spontaneous acetic fermentation. Acetic acid, glycerol, individual iridoids, phenolic acids, flavonols, and anthocyanins were quantified by a high-performance liquid chromatography (HPLC) method. The antioxidative activity was determined based on the following tests: 2,2-Diphenyl-2-picryl-hydrazyl (DPPH•), 2,2'-Azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS•+), and ferric reducing antioxidant power (FRAP), while the total polyphenols content was determined using the Folin-Ciocialteu (F-C) reagent test. Both the Cornelian cherry variety and vinegar production method affected the antioxidative properties as well as concentrations of iridoids and polyphenols in the finished product. The concentration of total polyphenols (F-C) in vinegars ranged from 326.60 to 757.27 mg gallic acids equivalents (GAE)/100 mL vinegar, whereas the antioxidative activity assayed with the DPPH•and FRAP methods was the highest in the vinegars produced from the coral and red varieties of Cornelian cherry with the two-stage method. Loganic acid predominated among the identified iridoids, reaching a concentration of 185.07 mg loganic acid (LA)/100 mL in the vinegar produced in the two-stage fermentation from the coral-fruit variety. Caffeoylquinic acid derivatives were the main representatives among the identified phenolic compounds. The results of this study demonstrate Cornelian cherry vinegars to be rich sources of biologically-active iridoids and phenolic compounds with antioxidative properties.
... Tomato vinegar decreased hepatic triglyceride and cholesterol levels and lowered plasma LDL-cholesterol level, thereby suggesting that it is an anti-obesity therapeutic agent or functional food . Beneficial effects of pomegranate vinegar beverage on adiposity were also reported by Park et al. (2014). These results prove the potential of lipidlowering effects of a variety of vinegars. ...
Chapter
This book, written by leading international authorities in the field, covers all the basic and applied aspects of acetic acid bacteria. It describes the importance of acetic acid bacteria in food industry by giving information on the microbiological properties of fermented foods as well as production procedures. Special attention is given to vinegar and cocoa, which are the most familiar and extensively used industrial applications of acetic acid bacteria. This book is an essential reference to all scientists, technologists, engineers, students and all those working in the field of food science and technology.
... Tomato vinegar decreased hepatic triglyceride and cholesterol levels and lowered plasma LDL-cholesterol level, thereby suggesting that it is an anti-obesity therapeutic agent or functional food . Beneficial effects of pomegranate vinegar beverage on adiposity were also reported by Park et al. (2014). These results prove the potential of lipidlowering effects of a variety of vinegars. ...
... Several animal and human studies have found that SCFAs can stimulate activation of AMPK in various tissues, including the liver [73][74][75]. In particular, an 8-wk study on healthy women supplemented with pomegranate vinegar demonstrated an increase AMPK phosphorylation in the adipose tissue [76]. When rats were supplemented with vinegar or acetic acid for 16 wk, there were also increases in AMPK phosphorylation (activation) in adipose as well as in the liver tissues [77]. ...
Article
Type 2 diabetes prevalence worldwide is increasing and the burden is particularly high in Asian countries. Identification of functional food ingredients to curb the rise of diabetes among various Asian population groups is warranted. Vinegar is widely consumed throughout Asia, where the principle bioactive component is acetic acid. This review has collated data from human intervention trials to show that vinegar consumption seems more effective in modulating glycaemic control in normal glucose tolerant individuals than in either type 2 diabetics or in those with impaired glucose tolerance. The molecular mechanisms by which vinegar can improve glycaemic control have been presented using human, animal and cell culture data. These mechanisms include (i) activation of the Free Fatty Acid Receptor 2 (FFAR2) receptors localised in the enteroendocrine L-cells of the intestinal lumen, leading to increased GLP-1 secretion, (ii) increased adenosine monophosphate kinase activation, leading to increased fatty acid oxidation and decreased hepatic gluconeogenesis, (iii) lowering of free fatty acid in circulation, potentially leading to improved insulin sensitivity, (iv) increased blood flow to the peripheral tissues and (v) increased satiety, leading to lower food intake. The review also discusses why these mechanisms are more effective in non-diabetics than in diabetics. This article is protected by copyright. All rights reserved.
... Many studies on vinegar obtained from the fermentation of fruit juices such as apple, strawberries and pomegranate have been actively performed (Cejudo Bastante et al. 2010;Naz{ro glu et al. 2014;Park et al. 2014). However, there are few studies on vinegar obtained from the fermentation of prickly pear. ...
Article
Context: Fruit vinegars (FVs) are used in Mediterranean folk medicine for their hypolipidemic and weight-reducing properties. Objective: To investigate the preventive effects of three types of FV, commonly available in Algeria, namely prickly pear [Opuntia ficus-indica (L.) Mill (Cectaceae)], pomegranate [Punica granatum L. (Punicaceae)], and apple [Malus domestica Borkh. (Rosaceae)], against obesity-induced cardiomyopathy and its underlying mechanisms. Materials and methods: Seventy-two male Wistar rats were equally divided into 12 groups. The first group served as normal control (distilled water, 7 mL/kg bw), and the remaining groups were respectively treated with distilled water (7 mL/kg bw), acetic acid (0.5% w/v, 7 mL/kg bw) and vinegars of pomegranate, apple or prickly pear (at doses of 3.5, 7 and 14 mL/kg bw, acetic acid content as mentioned above) along with a high-fat diet (HFD). The effects of the oral administration of FV for 18 weeks on the body and visceral adipose tissue (VAT) weights, plasma inflammatory and cardiac enzymes biomarkers, and in heart tissue were evaluated. Results: Vinegars treatments significantly (p < .05) attenuated the HFD-induced increase in bw (0.2–0.5-fold) and VAT mass (0.7–1.8-fold), as well as increase in plasma levels of CRP (0.1–0.3-fold), fibrinogen (0.2–0.3-fold), leptin (1.7–3.7-fold), TNF-α (0.1–0.6-fold), AST (0.9–1.4-fold), CK-MB (0.3–1.4-fold) and LDH (2.7–6.7-fold). Moreover, vinegar treatments preserved myocardial architecture and attenuated cardiac fibrosis. Discussion and conclusion: These findings suggest that pomegranate, apple and prickly pear vinegars may prevent HFD-induced obesity and obesity-related cardiac complications, and that this prevention may result from the potent anti-inflammatory and anti-adiposity properties of these vinegars.
... Pomegranate vinegar has high total acidity; several studies have shown that acetic acid (active component in all vinegars) down regulates ATP citrate lyase (ATP-CL), FAS, and ACC via sterol regulatory element-binding protein-1 (SREBP-1), thereby decreasing serum triglycerides levels in hyperlipidemic rats (Fushimi et al., 2006). An improvement in the lipid profile by vinegar was also observed in another study performed with human, mice, rats, and rabbits (Park et al., 2014;Setorki et al., 2010;Shishehbor et al., 2008;Soltan & Shehata, 2012). Fushimi et al. (2006) reported that serum TC was decreased when 0.3% (w/w) acetic acid was administrated for 19 d-routine diet containing 1% of cholesterol. ...
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Vinegar has long been used as a condiment and a traditional medicine worldwide. The current study investigates the antioxidant effect of three types of fruit vinegars (FV) namely pomegranate [Punica granatum L. (Punicaceae)], prickly pear [Opuntia ficus-indica (L.) Mill. (Cactaceae)], and apple [Malus domestica Borkh. (Rosaceae)] vinegars in high-fat diet (HFD)-induced hyperlipidemic Wistar rats. Fifty male Wistar rats were divided into five groups; HFD (80 cal/d) fed rats were orally dosed with fruit vinegars (7 ml/kg) once daily for 28 weeks. At the end of the experiment, lipid profile, lipid peroxidation products, antioxidant enzymes, and trace elements were assessed in serum. In addition, a liver histopathological study was performed. HFD showed a significant increase (p ≤ 0.05) in lipid profile and TBARS levels when compared with normal control. Daily oral administration of FV normalized various biochemical, metabolic, and histopathological changes. However, pomegranate vinegar exhibited a very significant (p ≤ 0.001) reduction in lipid profile levels (total cholesterol: 165%, triglycerides: 68%, LDL-c: 76%, and atherogenic index: 80%), whereas an increase in antioxidant status (SOD: 7-fold, GPx: 4.81-fold, GRx: 1.66-fold, and TAS: 3.45-fold) when compared with hyperlipidemic control. Histopathological examinations also confirmed the protective effects of pomegranate vinegar against lipid accumulation and the improvement of hepatic lesions. The fruit vinegars regulate lipid metabolism and decrease liver damage in high-fat fed rats as shown in this study.
... Phosphorylation of AMPK will induce PPAR-alpha gene expression [14] that regulates mRNA expression of fatty acid oxidation enzymes, such as acetyl-CoA (ACCA) oxidase and CPT-1a, which may enhance fatty acid boxidation. Activation of AMPK as well as down-regulation of SREBP-1c [29] and carbohydrate-responsive elementbinding protein (ChREBP) expression will inhibit lipid Therapeutic effect of vinegar: a review Samad, Azlan and Ismail 57 Table 1 Health benefits of different vinegar types. ...
... Pomegranate vinegar (PV) beverage tended to suppress downstream gene expression, such as that of sterol regulatory element binding protein-1c and acetyl coenzyme carboxylase, in adipose tissue. PV is an excellent AMP-activated protein kinase (AMPK) activator, and may exert beneficial effects on adiposity (Park et al., 2014). Tomato vinegar (TV) prevented obesity by suppressing visceral fat and lipid accumulation in adipocyte and obese rats, and TV can be used as an anti-obesity therapeutic agent or functional food . ...
Chapter
Bioactive compounds formed in situ or added during manufacture of fermented dairy foods, such as galacto-oligosaccharides (GOS), caseinophophopeptides (CPP) and conjugated linoleic acid (CLA) have shown to exert various biological activities affecting digestive, cardiovascular, immune and nervous systems. In particular, the prebiotic capacity of GOS, anticariogenic activity of CPP and anti-carcinogenic and anti-adipogenic effects of CLA, are some of the most important. GOS, non-digestible carbohydrates comprised of galactose and glucose, are produced by the activity of β-galactosidases enzymes on lactose. In turn, CPP are derived from caseins by the action of proteolytic enzymes (trypsin, quimotrypsin), and CLA is synthesized by microbial activity from its precursor fatty acid (mainly linoleic acid). This chapter presents an overview the current knowledge on technological approaches for manufacturing of fermented dairy foods enriched in GOS, CPP and CLA, as well as aspects concerning nutrition and health.
... Many studies on vinegar obtained from the fermentation of fruit juices such as apple, strawberries and pomegranate have been actively performed (Cejudo Bastante et al. 2010;Naz{ro glu et al. 2014;Park et al. 2014). However, there are few studies on vinegar obtained from the fermentation of prickly pear. ...
... In addition,Lee et al. (2013b)showed that tomato vinegar suppresses adipocyte differentiation and fat accumulation in 3T3-L1 cells and obese rat model. Many studies on vinegar obtained from the fermentation of fruit juices such as apple, strawberries and pomegranate have been actively performed (Cejudo Bastante et al. 2010;Naz{ro glu et al. 2014;Park et al. 2014). However, there are few studies on vinegar obtained from the fermentation of prickly pear. ...
... Pomegranate vinegar has high total acidity; several studies have shown that acetic acid (active component in all vinegars) down regulates ATP citrate lyase (ATP-CL), FAS, and ACC via sterol regulatory element-binding protein-1 (SREBP-1), thereby decreasing serum triglycerides levels in hyperlipidemic rats (Fushimi et al., 2006). An improvement in the lipid profile by vinegar was also observed in another study performed with human, mice, rats, and rabbits (Park et al., 2014; Setorki et al., 2010; Shishehbor et al., 2008; Soltan & Shehata, 2012). Fushimi et al. (2006) reported that serum TC was decreased when 0.3% (w/w) acetic acid was administrated for 19 d-routine diet containing 1% of cholesterol. ...
... Pomegranate juice is of great commercial potential as it is a source of many valuable bioactive compounds, such as phenolic compounds, organic acids, tannins (hydrolysable and condensed) and anthocyanins (Gil et al., 2000;Viuda-Martos et al., 2011;Mena et al., 2011;Akpinar-Bayizit et al., 2012;Hmid et al., 2017). Pomegranate juice as reported in previous studies can be used in soft drink formulations, other juices, syrups and fermented products (Maestre et al., 2000;Park et al., 2014). ...
Article
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Pomegranate tree is cultivated since ancient times in Morocco, where a high genetic diversity is hosted mainly in traditional agroecosystems. Over the past decade, it regained importance through extension of cultivated area, but remains thus far little valued. To date, its genetic variability and chemodiversity have gone unheeded for many reasons, some of which are related to previous agricultural strategies. In this context, the present study aimed to screen an ex-situ collection of seven local cultivars and seven exotic varieties with regard to 50 fruit morphometric and biochemical descriptors. The results showed statistically significant variability within accessions (p<0.01), based on all aforementioned traits, except for seed weight, with coefficients of variation greater than 49%. This indicated a high level of phenotypic diversity among the studied genetic pool. The 3D scatter plot built based on the principal component analysis displayed an interesting discrimination with regard to the genotypes’ geographic origins with a total variance of about 50%. According to morphometric based-heatmap, four main clusters were identified distinguishing the typicality of some local cultivars compared to exotic varieties, mainly ‘Sefri’, ‘Bzou’, ‘Chioukhi’ and ‘Djeibi’. Traits having the highest impact on discrimination between accessions were, by order of importance, fruit weight and its dimensions, juice yield, aril yield, single aril diameter, soluble sugars (glucose and fructose) along with contents in some organic acids, including citric, palmitic, linoleic and malic acids. Potential statistically significant correlations were spotted through bi-dimensional heatmap analysis, particularly between the fruit size, shape and peel traits along with some biochemical attributes. As many areas of the species chemodiversity and functional properties are still needed to be investigated further, the results of the present study are of great interest for the species valorization and for breeding programs.
... The present study is the first evidence to confirm that regular consumption of newly made beverage reduces body weight, body fat mass (Beh et al., 2017;Kondo et al., 2009;Park et al., 2014;Ryu et al., 2014;Wang et al., 2017). ...
Article
Vinegar and garlic are well‐known functional foods used in reducing obesity, Hence, a new beverage was developed from dates vinegar and garlic juice in order to reduce obesity. Current investigation focused on 85 obese adults. Participants consumed 500 mL of either beverage or placebo daily into their normal diet for a period of 10 weeks. Body weight, body mass index (BMI), waist circumference, visceral fat area (VFA), serum lipid profile, serum leptin, alanine transaminase (ALT), aspirate transaminase (AST), urea, and creatinine levels were analyzed before and after the treatment. The outcomes indicated that new beverage reduced the body weight (73.9 ± 6.7 to 69.6 ± 5.8 kg, p = .002), body fat ratio (29.8 ± 5.4 to 28.1 ± 4.2%, p = .004), and serum leptin (36.25 ± 3.2 to 31.12 ± 3.7 ng/mL, p = .002), and can therefore play a critical role in preclusion of metabolic syndrome. Practical applications Dates and garlic, compared with other fruits, are rich source of phenolic compounds and fibers. Researchers have claimed that extracts of dates fruit and garlic are effective in reducing obesity and prevention of metabolic syndrome. Thus, this study was conducted to determine the effects of a new beverage made of dates vinegar and garlic juice on obesity by assessing body weight, BMI, body fat mass, blood pressure, lipid profile, and liver markers. The results of this clinical trial present a latent approach to the avoidance of obesity and provide a possible source of phenolic compounds. This new beverage is suggested as a dietary supplement for the prevention of obesity and metabolic syndrome.
... Many natural, unmodified foods have been tested to probe its potential antidiabetic and/or antiobesity functionality; these group comprises vegetables, fruits or spices and have been found diverse results (Beidokhti and Jäger, 2017). Most of these studies have as test material vegetables (understood as any eatable part of a plant) and fruits of dark colors or very strong tastes; some of these materials are blueberry (Prior et al., 2010;Seymour et al., 2011;Mykkanen et al., 2014), blackberry (Kaume et al., 2012;Zanotti et al., 2015), grapes (Oueslati et al., 2016;Almomen et al., 2017), strawberries (McDougall et al., 2008;Basu et al., 2014), pomegranate (Ok et al., 2013;Park et al., 2014), cinnamon (Fabian et al., 2011;Okutan et al., 2014), ginger (Li et al., 2012), garlic (Lee et al., 2012;Moradabadi et al., 2013), among others. In the other hand, a wide different variety of bioactive compounds or food-obtained compounds/extracts (like essential oils or peel extracts) from foods have been used as potential functional foods ingredients or supplements instead unprocessed foods. ...
... Ayrıca farklı sirkelerin kan lipit-seviyesini düşürücü etkisi olduğu çeşitli çalışmalarla kanıtlanmıştır. Siyah sirke, domates sirkesi ve nar sirkesinin lipit düşürücü etkisinin bulunduğu ve antiobezite tedavisinde kullanılabilecek fonksiyonel bir ürün olduğu bildirilmektedir [28,110,111]. Yapılan araştırmalar, sirkenin antibakteriyel, antienfeksiyon ve antioksidan etkilerinin, yapısında bulunan organik asitler, polifenol ve melanoidinlerden kaynaklandığını, zengin asetik asit içeriğinin ise kan glukozunun kontrolü, lipit metabolizmasının düzenlenmesi ve kilo kaybına neden olduğunu ortaya koymuştur [112]. ...
Article
Vinegar is a special kind of condiment used as a flavoring and preservative agent in various foods since ancient times. Many types of vinegars are produced worldwide, especially in the Far East and European countries, using different raw materials and production techniques. Vinegar microflora mainly composed of acetic acid bacteria and yeasts, but some molds and lactic acid bacteria species can serve an important role in the production of various special vinegars. Vinegar shows many positive health effects, particularly antimicrobial, antioxidant, antidiabetic, antitumor, anticarcinogenic, antidiabetic and antiinfection effects, because of the substances found in vinegar such as organic acids, phenolic compounds, vitamins, minerals and melanoidins. In this review, recent studies on microflora, bioactive content and health effects of different kinds of vinegars are presented.
... [109,196,200,201] In vivo studies and clinical studies have supported the antioxidant, antihypertensive, anti-obesity, anti-diabetic, antihypercholesterolemic, immune stimulating, cardioprotective, and hepatoprotective properties of pomegranate. [109,196,[202][203][204][205][206][207][208] Nutraceutical and functional food products from P. granatum include 100% pomegranate juices, pomegranate-containing beverages, extracts of pomegranate plant parts such as leaves, flowers, seeds and peel, pomegranate seed oil, and skin care products containing pomegranate extracts and/or seed oil as main ingredient. [201,209] Turmeric: The golden medicine Curcuma longa L, commonly known as turmeric, is native to tropical South Asia and belongs to the Zingiberaceae family. ...
Article
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Nutraceuticals and natural health products globally represent one of the fastest growing sectors of research and development leading to novel products intended for disease risk reduction and human health promotion. The global nutraceutical market is expected to grow at a compound annual growth rate of 8.3% from 2020 to 2027 to reach USD 722.5 billion by 2027. There is a need to respond to this sector by exploring the local resources to target the production of innovative products from plant/marine biofactors with high prospects for commercial ventures. This paper explores the nutraceutical potentials enshrined in biodiversity values in a small island state in view to promote sustainable agricultural development to facilitate available resources for the development of regimen for the management of health and disease and in essence, pharmacotherapy. The reported phytochemical composition and pharmacological activities, of the terrestrial flora and marine organisms with high propensity for development and production of nutraceutical products will be discussed. Bioactive phytochemicals encompassing the immensely diverse groups of phenolic acids, flavonoids, terpenoids, alkaloids, possess therapeutic virtues including anti-diabetic, antihypertensive, anticancer, anti-inflammatory, and immunomodulatory attributes, all of which are highly relevant to the budding nutraceutical industry.
... Also, in a randomized, double-blind clinical trial on 20 obese subjects, treatment with PJ (120 ml) reduced adiposity but did not modify insulin secretion and sensitivity [146]. Park et al. indicated that the intake of pomegranate vinegar (700 μg ellagic acid/200 mL/day and 1.5 g acetic acid for 8 weeks) by 78 overweight women led to a reduction in visceral adipose tissue and an increase in AMP-activated protein kinase phosphorylation [147]. In general, consumption of pomegranate juice/extract may prevent obesity and its related disorders. ...
Article
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Punica granatum L. belongs to the Punicaceae family which is distributed around the world. Different parts of pomegranate like seed, peel, juice, and leaves are rich in potential bioactive compounds. These plants have found application in traditional medicine such as in treatment of gastrointestinal, cardiovascular, and endocrine diseases, among others. The present review aimed to summarize the current research on the traditional and scientific applications of P. granatum with regard to the phytochemical content and clinical applications that may be useful for future drug development. Information about P. granatum was obtained from local classic herbal literature and electronic databases, such as PubMed, Scopus, and ScienceDirect. Several phytochemical constituents including polyphenolics, flavonoids, anthocyanosides, alkaloids, lignans, and triterpenes have been reported from the plant. Randomized clinical trials have provided evidence as to the pharmacological activities of pomegranate in several diseases including diabetes, cardiovascular disease, oral cavity disorders, endocrine disorders, and cancer. The present review has provided an insight into the traditional applications of the plants, and some of them have been validated by scientific evidence, particularly their applications as treatment of cardiovascular and endocrine diseases.
... [109,196,200,201] In vivo studies and clinical studies have supported the antioxidant, antihypertensive, anti-obesity, anti-diabetic, antihypercholesterolemic, immune stimulating, cardioprotective, and hepatoprotective properties of pomegranate. [109,196,[202][203][204][205][206][207][208] Nutraceutical and functional food products from P. granatum include 100% pomegranate juices, pomegranate-containing beverages, extracts of pomegranate plant parts such as leaves, flowers, seeds and peel, pomegranate seed oil, and skin care products containing pomegranate extracts and/or seed oil as main ingredient. [201,209] Turmeric: The golden medicine Curcuma longa L, commonly known as turmeric, is native to tropical South Asia and belongs to the Zingiberaceae family. ...
Article
Full-text available
Nutraceuticals and natural health products globally represent one of the fastest growing sectors of research and development leading to novel products intended for disease risk reduction and human health promotion. The global nutraceutical market is expected to grow at a compound annual growth rate of 8.3% from 2020 to 2027 to reach USD 722.5 billion by 2027. There is a need to respond to this sector by exploring the local resources to target the production of innovative products from plant/marine biofactors with high prospects for commercial ventures. This paper explores the nutraceutical potentials enshrined in biodiversity values in a small island state in view to promote sustainable agricultural development to facilitate available resources for the development of regimen for the management of health and disease and in essence, pharmacotherapy. The reported phytochemical composition and pharmacological activities, of the terrestrial flora and marine organisms with high propensity for development and production of nutraceutical products will be discussed. Bioactive phytochemicals encompassing the immensely diverse groups of phenolic acids, flavonoids, terpenoids, alkaloids, possess therapeutic virtues including anti-diabetic, antihypertensive, anticancer, anti-inflammatory, and immunomodulatory attributes, all of which are highly relevant to the budding nutraceutical industry.
... The production of vinegar has two fermentation steps: the alcohol fermentation by using yeast convert sugar to alcohol in anaerobic conditions followed by acetous fermentation to form acetic acid with Acetobacter and Gluconobacter in the aerobic condition and the acetic acid content of vinegar is not less than 4%, In the cell, acetic acid was absorbed from the intestine and metabolized to acetyl CoA in the liver, fructified in the feed-forward activation of Adenosine Monophosphate (AMP)-activated protein kinase (AMPK). AMPK was a member of the metabolite-sensing protein kinase family and has been related to the regulation of enzyme activities involved in energy metabolism thus, AMPK has been recognized as a promising target for the management of obesity [7,8]. Nowadays, fermented vinegar is a popular beverage as a drink with honey and warm water to help the digestive system better. ...
Article
Full-text available
This study was conducted to produce fermented vinegar from two types of pomegranate, namely Chinese and Indian cultivar. The aim of the present study was to examine the chemical properties of vinegar and its antioxidant activities. From the fermentation of wine for 9 days, Chinese pomegranate wine had 9.95 ± 0.28 percent of alcohol content. The highest antioxidant activities and total phenolic content observed for the wine produced from the Indian cultivar were 32.58 ± 0.68 mg/mL and 536.73 mg/L, respectively. Vinegar fermentation was operated by inoculating 10% (v/v) of Acetobacter pasteurianus into two pomegranate wines with their start alcohol content adjusted to 4% (v/v). The fermentation was proceeded for 15 days at 30 º C and sampling was operated at 5-day intervals. It was remarked for all samples that the level of alcohol decreased continuously over the fermentation period, While the amount of acetic acid increased. At the end of the fermentation process, the fermented vinegar produced from the Chinese cultivar showed the highest level of acetic acid of 7.50 ± 0.21%. The highest antioxidant activities and total phenolic content observed for the vinegar produced from the Indian cultivar were 35.25 ± 0.90 mg/mL and 480.24 ± 28.82 mg/L, respectively. The 9-point hedonic scale showed that the vinegar produced from Indian pomegranate exhibited the highest overall acceptability (7.63 ± 1.24), which indicated the very much pleasant level of the vinegar preference of the consumers.
... The production of vinegar has two fermentation steps: the alcohol fermentation by using yeast convert sugar to alcohol in anaerobic conditions followed by acetous fermentation to form acetic acid with Acetobacter and Gluconobacter in the aerobic condition and the acetic acid content of vinegar is not less than 4%, In the cell, acetic acid was absorbed from the intestine and metabolized to acetyl CoA in the liver, fructified in the feed-forward activation of Adenosine Monophosphate (AMP)-activated protein kinase (AMPK). AMPK was a member of the metabolite-sensing protein kinase family and has been related to the regulation of enzyme activities involved in energy metabolism thus, AMPK has been recognized as a promising target for the management of obesity [7,8]. Nowadays, fermented vinegar is a popular beverage as a drink with honey and warm water to help the digestive system better. ...
Article
This study was conducted to produce fermented vinegar from two types of pomegranate, namely Chinese and Indian cultivar. The aim of the present study was to examine the chemical properties of vinegar and its antioxidant activities. From the fermentation of wine for 9 days, Chinese pomegranate wine had 9.95 ± 0.28 percent of alcohol content. The highest antioxidant activities and total phenolic content observed for the wine produced from the Indian cultivar were 32.58 ± 0.68 mg/mL and 536.73 mg/L, respectively. Vinegar fermentation was operated by inoculating 10% (v/v) of Acetobacter pasteurianus into two pomegranate wines with their start alcohol content adjusted to 4% (v/v). The fermentation was proceeded for 15 days at 30 º C and sampling was operated at 5-day intervals. It was remarked for all samples that the level of alcohol decreased continuously over the fermentation period, While the amount of acetic acid increased. At the end of the fermentation process, the fermented vinegar produced from the Chinese cultivar showed the highest level of acetic acid of 7.50 ± 0.21%. The highest antioxidant activities and total phenolic content observed for the vinegar produced from the Indian cultivar were 35.25 ± 0.90 mg/mL and 480.24 ± 28.82 mg/L, respectively. The 9-point hedonic scale showed that the vinegar produced from Indian pomegranate exhibited the highest overall acceptability (7.63 ± 1.24), which indicated the very much pleasant level of the vinegar preference of the consumers.
... In the meta-analysis for triglyceride levels in overweight or obese adults, where acetic acid is compared to placebo or low-dose acetic acid, three studies are included [2][3][4] . However, perusing the data from the third study 4 (study ID 'Park 2014' in Figure 1), the follow-up values in the meta-analysis have been swapped between intervention group and control group. ...
Article
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Correspondence on ‘D.S. Valdes, D. So, P.A. Gill, N.J. Kellow, Effect of Dietary Acetic Acid Supplementation on Plasma Glucose, Lipid Profiles, and Body Mass Index in Human Adults: A Systematic Review and Meta-analysis., J. Acad. Nutr. Diet. (2021). https://doi.org/10.1016/j.jand.2020.12.002’ Note: The editor-in-chief forwarded my letter to the authors who will implement my suggestions in a corrigendum to the original article. To avoid redundancy, my letter will not be published, and instead credits to me will be included in the author’s corrigendum. The editor full email is reported at the end of the full document.
... Two non-randomized studies conducted in T2D participants found mixed results for fasting plasma glucose [64,65]. The bulk of randomized clinical trials on the topic [63,[66][67][68][69][70][71][72][73][74][75][76] reported on neutral results, except for a study conducted in healthy patients, in which 4-week consumption of pomegranate juice lowered fasting plasma insulin and HOMA-IR compared to a control with equivalent amount of carbohydrates [69]. Pomegranate extracts were also used in several randomized clinical trials, but none of them included individuals with T2D (Table 1) [62,77,78]. ...
Article
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Oxidative stress contributes not only to the pathogenesis of type 2 diabetes (T2D) but also to diabetic vascular complications. It follows that antioxidants might contribute to limiting the diabetes burden. In this review we focus on ellagic acid (EA), a compound that can be obtained upon intestinal hydrolysis of dietary ellagitannins, a family of polyphenols naturally found in several fruits and seeds. There is increasing research on cardiometabolic effects of ellagitannins, EA, and urolithins (EA metabolites). We updated research conducted on these compounds and (I) glucose metabolism; (II) inflammation, oxidation, and glycation; and (III) diabetic complications. We included studies testing EA in isolation, extracts or preparations enriched in EA, or EA-rich foods (mostly pomegranate juice). Animal research on the topic, entirely conducted in murine models, mostly reported glucose-lowering, antioxidant, anti-inflammatory, and anti-glycation effects, along with prevention of micro-and macrovascular diabetic complications. Clinical research is incipient and mostly involved non-randomized and low-powered studies, which confirmed the antioxidant and anti-inflammatory properties of EA-rich foods, but without conclusive results on glucose control. Overall, EA-related compounds might be potential agents to limit the diabetes burden, but well-designed human randomized controlled trials are needed to fill the existing gap between experimental and clinical research.
... Several studies have been conducted on the effectiveness of pomegranate peel extract (PPE) and its bioactive compounds in the prevention and treatment of obesity and associated comorbidities (15,16) . PPE, its phenolic compounds and their metabolites generated by gut microbiota have shown to favour biogenesis and mitochondrial function among other beneficial metabolic effects in obesity models (15,17,18) . ...
Article
Pomegranate peel is an agro-industrial residue obtained after fruit processing, with no commercial fate. It has a high total polyphenol (TP) content, which makes it an attractive by-product for its reuse. Pomegranate peel extract (PPE) and its bioactive compounds have shown positive effects on obesity models. Effects on favoring mitochondrial biogenesis and function have also been described. However, once extracted, the stability of this matrix can be affected by diverse factors. Microencapsulation could improve PPE stability, allowing its incorporation in mice's diet, among other applications. Nevertheless, studies regarding the potential biological effects of PPE microparticles (MPPE) in obesity models are lacking. The present study aims to evaluate the effect of MPPE on brown adipose tissue (BAT) mitochondrial structure and function, and on metabolic alterations related to obesity in mice fed a high-fat diet (HFD). PPE was microencapsulated by spray drying using inulin (IN) as a coating material, and physically-chemically characterized. 8-week-old male C57BL/6J mice (n=40) were randomly distributed into five groups: control diet (CD); HFD; HFD+IN; HFD+PPE (50 mg/kg/d TP); HFD+MPPE (50 mg/kg/d TP), for 14 weeks. A glucose tolerance test and indirect calorimetry were conducted. MPPE supplementation prevented HFD-induced body weight gain (p=0.0007), and fasting glycemia (p=0.0072) and total cholesterol rise (p=0.0013). MPPE resulted in higher BAT mitochondrial complex IV activity (p=0.035) and prevented HFD-induced mitochondrial cristae alteration (p=0.025). In conclusion, MPPE prevented HFD-induced body weight gain and associated metabolic disturbances, potentially by activating complex IV activity and preserving mitochondrial cristae morphology in BAT in mice fed on a HFD.
... obesity and anti-diabetic activity (Johnston et al., 2013;Yusoff et al., 2015) and lipid lowering effects (Lee et al., 2013;Park et al., 2014). In general, vinegar is produced based on a double fermentation process, namely, alcohol fermentation and acetic acid fermentation (Ozturk et al., 2015;Ubeda et al., 2016). ...
Article
Full-text available
Fruit and vegetable waste has been widely utilized as a low-cost natural source for vinegar production. In this study, the pulp of banana (Musa acuminata ‘Gros Michel’) cv. ‘Hom Thong’ was utilized to produce vinegar using one-stage (acetous) and two-stage (alcoholic and acetous) fermentation and the obtained vinegars were assessed for their physicochemical properties, antioxidant activities and polyphenolic contents. It was found that the one-stage fermentation yielded greater levels of acetic acid (5.83% volume per volume; v/v) than two-stage fermentation (5.13% v/v). The 2,2-diphenyl-1-picrylhydrazyl hydrate and ferric reducing/antioxidant power assays, respectively, indicated that the antioxidant activity of the one-stage fermented vinegars (80.27% and 1274 μM Fe(II)/L) was greater than that of the two-stage fermented vinegars (73.20%, 1001 μM Fe(II)/L). In a similar manner, the polyphenolic content of the one-stage fermented vinegars (92.67 μg/mL) was higher than that of the two-stage fermented vinegars (68.01 μg/mL). The color parameters (L*, a*, b*) only showed significant differences in a* for the color change of the vinegars aged during days 0–100 for the one- and two-stage fermented vinegars. Moreover, it was observed that the one-stage fermented vinegars had higher levels of acetic acid, antioxidant activity and polyphenolics contents than the two-stage fermented vinegars. The results suggested that the use of banana pulp to produce vinegar via one-stage fermentation is a good choice to retain the bioactive compounds.
... Pomegranate vinegar (PV) beverage tended to suppress downstream gene expression, such as that of sterol regulatory element binding protein-1c and acetyl coenzyme carboxylase, in adipose tissue. PV is an excellent AMP-activated protein kinase (AMPK) activator, and may exert beneficial effects on adiposity (Park et al., 2014). Tomato vinegar (TV) prevented obesity by suppressing visceral fat and lipid accumulation in adipocyte and obese rats, and TV can be used as an anti-obesity therapeutic agent or functional food . ...
... The lack of knowledge about the possible mechanism of pomegranate could be described by the diversity of fruit ingredients. 43,44 The antioxidant power of compounds found in pomegranate is proven in extensive in vitro and animal studies. 45 Tannins and polyphenols present in pomegranate considered as factors affecting the antioxidant properties of pomegranate. ...
Article
Objective Pomegranate contains remarkable amounts of phenolic ingredients and it has been related to the antioxidant capacity of this fruit. Several primary studies show that pomegranate intake can improve antioxidant status. The objective of this systematic review and meta-analysis consisted in investigating the effect of pomegranate on oxidative stress (OS) parameters. Methods A comprehensive electronic database search in Scopus, Web of science, Embase, Cochrane library and Medline was performed to identify eligible randomized controlled trials (RCTs). A meta-analysis of included studies was performed on selected variables using a random-effects model. Quality assessment was conducted by means of Cochrane risk of bias assessment tool. Results Systematic search yielded 575 references. A total of 11 RCTs reporting data from 484 participants included. Meta-analysis of data from 11 included RCTs did not support convincing evidence as to a significant increasing effect of pomegranate intake in TAC (SMD: 0.43 ; 95 %CI: -0.19, 1.06), Gpx (SMD: 0.18, 95 % CI: -0.25, 0.62, p = 0.4) and paraxonase (SMD: 0.36, 95 % CI: -0.50, 1.22, p= 0.41) as well as not significant decrease in Malondialdehyde (MDA) (SMD: -0.81, 95 % CI: -1.79, 0.09, P = 0.08). Conclusion Future well-designed clinical trials are needed before definite conclusive claims can be made about the effect of pomegranate on OS parameters.
... Pascual-Teresa, Santos-Buelga, & Rivas-Gonzalo, 2004;Madrigal-Carballo, Rodriguez, Krueger, Dreher, & Reed, 2009;Ordoudi et al., 2014) and might induce health benefits against cancer, cardiovascular and other health problems (Basu & Penugonda, 2009;Park et al., 2014;Wu, Ma, & Tian, 2013). Additionally, pomegranate peel contains a high amount of ellagic acid, ellagitannins, such as punicalin and punicalagin, as well as hexahydroxydiphenic acid (HHDP) which possess antiinflammatory, antitumor, and apoptotic properties (Seeram, Lee, Hardy, & Heber, 2005). ...
Article
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Major derivatives of ellagic acid and antioxidant properties of 9 Spanish pomegranate cultivars were studied at two development stages: thinning and ripening. A total of 35 major derivatives of ellagic acid were identified by LC-PDA–QTOF/MS and quantified by UPLC-PDA methods; however, only 7 of them were found simultaneously in thinning and ripe fruits. The total content of derivatives of ellagic acid was higher in thinning fruits (3521–18,236 mg 100 g−1 dry matter, dm) than in ripe fruits (608–2905 mg 100 g−1 dm). Ripe fruits had lower values of the antioxidant activities than thinning fruits. In general, sour–sweet cultivars (PTO8 cultivar) had the highest value of derivatives of ellagic acid and antioxidant properties in pomegranates fruits. Experimental results clearly proved the potential of thinning pomegranate fruits for its use as supplement in food, pharmaceutical and cosmetics industries.
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Previous studies have suggested that vinegar intake can help to reduce body fat and hyperglycemia. Therefore, this study aimed to evaluate the anti-obesity efficacy of vinegar fermented using Cudrania tricuspidata fruits (CTFV) and its main phenolic constituents and to analyze its molecular mechanism and changes in obesity-related metabolizing enzymatic activities. We found that HFD significantly caused hepatic steatosis; increases in body fats, feed efficiency, liver mass, lipids, insulin, oxidative parameters, cardiovascular-associated risk indices, lipase and α-amylase activities, whereas CTFV efficaciously attenuated HFD-induced oxidant stress, fat accumulation, obesity-related enzymatic activity, and the activation or reduction of obesity-related molecular reactions via improving metabolic parameters including phosphorylated insulin receptor substrate 1, protein tyrosine phosphatase 1B, phosphorylated phosphoinositide 3-kinase/protein kinase B, phosphorylated mitogen-activated protein kinases, sterol regulatory element-binding protein 1c, CCAAT/enhancer-binding protein, and fatty acid synthase; and decreases in adiponectin receptor 1, leptin receptor, adenosine monophosphate-activated protein kinase, acetyl-CoA carboxylase, and peroxisome proliferator-activated receptor, subsequently ameliorating HFD-induced obesity. Therefore, CTFV might provide a functional food resource or nutraceutical product for reducing body fat accumulation.
Article
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Nine pomegranate cultivars grown in Spain were selected, and their physicochemical (total soluble solids, pH, titratable acidity, maturity index, monomeric anthocyanin pigment, flavonoids, hydrolyzable tannins, and vitamin C) and antioxidant properties and polyphenolic composition of the juices were compared. A total of 53 polyphenols were identified, showing cultivars different profiles. Of all nine cultivars, Katirbasi had the highest contents of flavonoids, hydrolyzable tannins and vitamin C, as well as gallic acid and ellagic acid contents, explaining its high total reducing capacity. Principal component analysis allowed Katirbasi to be differentiated clearly from the others. Other cultivars presented also interesting characteristics such as high monomeric anthocyanin pigment content (CG8 cultivar) and interesting antioxidant activity (Wonderful 2 and CG8 cultivars). CG8 was the cultivar with the highest value of cyanidin-3,5-di-O-glucoside. Thus, this study will assist pomegranate producers in choosing the most suitable cultivar according to its ultimate use.
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In the past, the beneficial effects of fermented foods on health were unknown, and so people primarily used fermentation to preserve foods, enhance shelf life, and improve flavour. Fermented foods became an important part of the diet in many cultures, and over time fermentation has been associated with many health benefits. Because of this, the fermentation process and the resulting fermented products have recently attracted scientific interest. In addition, microorganisms contributing to the fermentation process have recently been associated with many health benefits, and so these microorganisms have become another focus of attention. Lactic acid bacteria (LAB) have been some of the most studied microorganisms. During fermentation, these bacteria synthesize vitamins and minerals, produce biologically active peptides with enzymes such as proteinase and peptidase, and remove some non-nutrients. Compounds known as biologically active peptides, which are produced by the bacteria responsible for fermentation, are also well known for their health benefits. Among these peptides, conjugated linoleic acids (CLA) have a blood pressure lowering effect, exopolysaccharides exhibit prebiotic properties, bacteriocins show anti-microbial effects, sphingolipids have anti-carcinogenic and anti-microbial properties, and bioactive peptides exhibit anti-oxidant, anti-microbial, opioid antagonist, anti-allergenic, and blood pressure lowering effects. As a result, fermented foods provide many health benefits such as anti-oxidant, anti-microbial, anti-fungal, anti-inflammatory, anti-diabetic and anti-atherosclerotic activity. However, some studies have shown no relationship between fermented foods and health benefits. Therefore, this paper aims to investigate the health effects of fermented foods.
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Background: Transport of oxidized low-density lipoprotein across the endothelium into the artery wall is considered a fundamental priming step for the atherosclerotic process. Recent studies reported potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic cardiovascular disease driven by cardiovascular risk factors and oxidative stress. A particular attention has been recently addressed to pomegranate; however findings of clinical studies have been contrasting. Purpose: To evaluate the effects of pomegranate consumption on plasma lipid concentrations through a systematic review and meta-analysis of randomized controlled trials (RCTs). Methods: The study was designed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Scopus and Medline databases were searched to identify randomized placebo-controlled trials investigating the impact of pomegranate on plasma lipid concentrations. A fixed-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. Results: A total of 545 individuals were recruited from the 12 RCTs. Fixed-effect meta-analysis of data from 12 RCTs (13 treatment arms) did not show any significant effect of pomegranate consumption on plasma lipid concentrations. The results of meta-regression did not suggest any significant association between duration of supplementation and impact of pomegranate on total cholesterol and HDL-C, while an inverse association was found with changes in triglycerides levels (slope: -1.07; 95% CI: -2.03 to -0.11; p = 0.029). There was no association between the amount of pomegranate juice consumed per day and respective changes in plasma total cholesterol, LDL-C, HDL-C and triglycerides. Conclusion: The present meta-analysis of RCTs did not suggest any effect of pomegranate consumption on lipid profile in human.
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Background The potential glucose-lowering effects of pomegranate have been reported in animal and observational studies, but intervention studies in humans have generated mixed results. In this paper, we aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the precise effects of pomegranate supplementation on measures of glucose control, insulin levels and insulin sensitivity in humans. Methods Comprehensive electronic searches were conducted in PubMed, Embase, and the Cochrane Library. Studies included were RCTs that evaluated the changes in diabetes biomarkers among adults (≥18 years) following pomegranate interventions. The predefined outcomes included fasting blood glucose (FBG), fasting blood insulin (FBI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA-IR). Endpoints were calculated as weighted mean differences (WMDs) with 95% confidence intervals (CIs) by using a random-effects model. Publication bias, subgroup analyses, sensitivity analysis and random-effects meta-regression were also performed to explore the influence of covariates on the net changes in fasting glucose and insulin concentrations. Results Sixteen eligible trials with 538 subjects were included. The pooled estimates suggested that pomegranate did not significantly affect the measures of FBG (WMD, −0.6 mg/dL; 95% CI, −2.79 to 1.58; P=0.59), FBI (WMD, 0.29 μIU/mL; 95% CI, −1.16 to 1.75; P=0.70), HOMA-IR (WMD, −0.04; 95% CI, −0.53 to 0.46; P=0.88) or HbA1c (WMD, −0.11%; 95% CI, −0.39 to −0.18; P=0.46). Overall, significant heterogeneity was detected for FBI and HOMA-IR, but subgroup analysis could not identify factors significantly influencing these parameters. These results were robust in sensitivity analysis, and no significant publication bias was found in the current meta-analysis. Conclusion Pomegranate intake did not show a notably favourable effect on improvements in glucose and insulin metabolism. The current evidence suggests that daily pomegranate supplementation is not recommended as a potential therapeutic strategy in glycemic management. Further large-scale RCTs with longer duration are required to confirm these results. Electronic supplementary material The online version of this article (10.1186/s12937-017-0290-1) contains supplementary material, which is available to authorized users.
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Understanding interindividual variability in response to dietary polyphenols remains essential to elucidate their effects on cardiometabolic disease development. A meta-analysis of 128 randomized clinical trials was conducted to investigate the effects of berries and red grapes/wine as sources of anthocyanins and of nuts and pomegranate as sources of ellagitannins on a range of cardiometabolic risk biomarkers. The potential influence of various demographic and lifestyle factors on the variability in the response to these products were explored. Both anthocyanin- and ellagitannin-containing products reduced total-cholesterol with nuts and berries yielding more significant effects than pomegranate and grapes. Blood pressure was significantly reduced by the two main sources of anthocyanins, berries and red grapes/wine, whereas waist circumference, LDL-cholesterol, triglycerides, and glucose were most significantly lowered by the ellagitannin-products, particularly nuts. Additionally, we found an indication of a small increase in HDL-cholesterol most significant with nuts and, in flow-mediated dilation by nuts and berries. Most of these effects were detected in obese/overweight people but we found limited or non-evidence in normoweight individuals or of the influence of sex or smoking status. The effects of other factors, i.e., habitual diet, health status or country where the study was conducted, were inconsistent and require further investigation.
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The vinegar pei harbors complex bacterial communities. Prior studies revealing the bacterial diversity involved were mainly conducted by culture-dependent methods and PCR-DGGE. In this study, 454 pyrosequencing was used to investigate the bacterial communities in vinegar pei during the acetic acid fermentation (AAF) of Tianjin Duliu aged vinegar (TDAV). The results showed that there were 7 phyla and 24 families existing in the vinegar pei, with 2 phyla (Firmicutes, Protebacteria) and 4 families (Lactobacillaceae, Acetobacteracae, Enterobacteriaceae, Chloroplast) predominating. The genus-level identification revealed that 9 genera were the relatively stable, consistent components in different stages of AAF, including the most abundant genus Lactobacillus followed by Acetobacter and Serratia. Additionally, the bacterial community in the early fermentation stage was more complex than those in the later stages, indicating that the accumulation of organic acids provided an appropriate environment to filter unwanted bacteria and to accelerate the growth of required ones. This study provided basic information of bacterial patterns in vinegar pei and relevant changes during AAF of TDAV, and could be used as references in the following study on the implementation of starter culture as well as the improvement of AAF process.
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Antecedentes: La enfermedad por hígado graso no alcohólico (EHGNA) tiene una elevada prevalencia a nivel mundial, y puede ir desde la esteatosis simple hasta hepatocarcinoma. Su origen es multifactorial, siendo la dieta poco saludable un factor clave en su patogenia y progresión. Los polifenoles son antioxidantes que han mostrado beneficios en el tratamiento de la EHGNA. Una fuente emergente de estos compuestos son los residuos agroindustriales, entre ellos, la cáscara de granada. La cáscara de granada tiene un alto contenido de polifenoles, específicamente de elagitaninos. Su extracto fenólico (extracto de cáscara de granada; ECG) ha mostrado efectos promisorios a nivel metabólico. Sin embargo, su uso presenta algunas limitantes que deben ser consideradas antes de recomendar su ingesta mediante alimentos funcionales o nutracéuticos para prevención o tratamiento de EHGNA. Objetivo: Discutir a partir de datos obtenidos en estudios in vitro y modelos animales, el potencial terapéutico de los polifenoles obtenidos de la cáscara de granada para prevención y tratamiento de la EHGNA. Metodología: Se realizó una búsqueda bibliográfica en bases de datos PubMed y Web of Science (2015 a la fecha) de estudios en modelos de esteatosis hepática in vitro y en animales, además de ensayos clínicos relacionados. Conclusión: Existen datos promisorios sobre el uso del ECG en alteraciones metabólicas propias de la EHGNA y esteatosis hepática, principalmente a nivel de perfil lipídico. Se deben discutir las dosis y formas de administración, con el fin de mejorar su estabilidad y biodisponibilidad. Se requieren ensayos clínicos controlados que confirmen los efectos en humanos.
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The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid) and BML-275 (an AMPKα inhibitor). Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.
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The effect of pomegranate vinegar (PV) on adiposity was investigated in high-fat diet (HF)-induced obese rats. The rats were divided into 5 groups and treated with HF with PV or acetic acid (0, 6.5 or 13% w/w) for 16 weeks. Statistical analyses were performed by the Statistical Analysis Systems package, version 9.2. Compared to control, PV supplementation increased phosphorylation of AMP-activated protein kinase (AMPK), leading to changes in mRNA expressions: increases for hormone sensitive lipase and mitochondrial uncoupling protein 2 and decreases for sterol regulatory element binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptorgamma (PPARgamma) in adipose tissue; increases for PPARalpha and carnitinepalmitoyltransferase-1a (CPT-1a) and decrease for SREBP-1c in the liver. Concomitantly, PV reduced increases of body weight (p = 0.048), fat mass (p = 0.033), hepatic triglycerides (p = 0.005), and plasma triglycerides (p = 0.001). These results suggest that PV attenuates adiposity through the coordinated control of AMPK, which leads to promotion of lipolysis in adipose tissue and stimulation of fatty acid oxidation in the liver.
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We investigated whether the combination of phytochemicals and acetic acid in the form of fruit vinegar provides an additive effect on changes of mRNA levels related to fatty acid oxidation in human hepatocyte (HepG2). Among the seven fruit vinegars (Rubuscoreanus, Opuntia, blueberry, cherry, red ginseng, mulberry, and pomegranate) studied, treatment of HepG2 with pomegranate vinegar (PV) at concentrations containing 1 mM acetic acid showed the highest in vitro potentiating effect on the mRNA expression levels of peroxisome proliferator-activated receptor α, carnitinepalmitoyl transferase-1, and acyl-CoA oxidase compared to the control group (P < 0.05). Reversed-phase liquid chromatography in combination with quadrupole time-of-flight mass spectrometry analysis revealed four potential compounds (punicalagin B, ellagic acid, and two unidentified compounds) responsible for altered gene expression in HepG2 cells treated with PV as compared with the others. Further investigations are warranted to determine if drinking PV beverages may help to maintain a healthy body weight in overweight subjects.
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Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation through up-regulating the protein levels of liver kinase B1. Activated AMPKα increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα). NEFAs also directly activate the PPARα independent of AMPKα. Activated PPARα increased the lipolytic genes expression to increase lipid oxidation. Furthermore, activated AMPKα inhibited the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid synthesis. Activated AMPKα phosphorylated and inhibited acetyl-CoA carboxylase and increased carnitine palmitoyltransferase-1 activity, which increased lipid oxidation. Consequently, the triglyceride content in the NEFAs-treated hepatocytes was significantly decreased. These results indicate that NEFAs activate the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in hepatocytes, which in turn, generates more ATP to relieve the negative energy balance in transition dairy cows.
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AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP. Although best known for its effects on metabolism, AMPK has many other functions, including regulation of mitochondrial biogenesis and disposal, autophagy, cell polarity, and cell growth and proliferation. Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth.
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Lysimachia foenum-graecum has been used as an oriental medicine with anti-inflammatory effect. The anti-obesity effect of L. foenum-graecum extract (LFE) was first discovered in our screening of natural product extract library against adipogenesis. To characterize its anti-obesity effects and to evaluate its potential as an anti-obesity drug, we performed various obesity-related experiments in vitro and in vivo. In adipogenesis assay, LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 2.5 μg/ml. In addition, LFE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes in vitro at 10 μg/ml and in vivo at 100 mg/kg/day. The anti-adipogenic and anti-lipogenic effect of LFE seems to be mediated by the inhibition of PPARγ and C/EBPα expression as shown in in vitro and in vivo, and the suppression of PPARγ activity in vitro. Moreover, LFE stimulated fatty acid oxidation in an AMPK-dependent manner. In high-fat diet (HFD)-induced obese mice (n = 8/group), oral administration of LFE at 30, 100, and 300 mg/kg/day decreased total body weight gain significantly in all doses tested. No difference in food intake was observed between vehicle- and LFE-treated HFD mice. The weight of white adipose tissues including abdominal subcutaneous, epididymal, and perirenal adipose tissue was reduced markedly in LFE-treated HFD mice in a dose-dependent manner. Treatment of LFE also greatly improved serum levels of obesity-related biomarkers such as glucose, triglycerides, and adipocytokines leptin, adiponectin, and resistin. All together, these results showed anti-obesity effects of LFE on adipogenesis and lipid metabolism in vitro and in vivo and raised a possibility of developing LFE as anti-obesity therapeutics.
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To investigate whether the insulin resistance index (IR) assessed by homeostasis model assessment (HOMA) is associated with the insulin resistance index assessed by euglycemic-hyperinsulinemic clamp (clamp IR) in type 2 diabetic patients who received sulfonylureas (SUs), as well as in those treated by diet alone. Retrospectively, the association between HOMA IR and clamp IR was analyzed in 80 type 2 diabetic subjects (53 subjects treated with SUs and 27 subjects treated with diet alone). The 80 subjects, selected because they had not received insulin therapy, were among 111 diabetic participants in a clamp study for evaluation of insulin resistance from May 1993 to December 1997 in Osaka City University Hospital. The HOMA IR showed a hyperbolic relationship with clamp IR. The log-transformed HOMA IR (all subjects, r = -0.725, P < 0.0001; SU group, r = -0.727, P < 0.0001; diet group, r = -0.747, P < 0.0001) correlated more strongly with clamp IR than did HOMA IR per se (all subjects, r = -0.594, P < 0.0001; SU group, r = -0.640, P < 0.0001; diet group, r = -0.632, P = 0.0004). The univariate regression line between log-transformed HOMA IR and clamp IR in the SU group did not differ from that in the diet group (slope, -6.866 vs. -5.120, P > 0.05; intercept, 6.566 vs. 5.478, P > 0.05). Stepwise multiple regression analyses demonstrated that the log-transformed HOMA IR was the strongest independent contributor to clamp IR (R2 = 0.640, P < 0.0001). The HOMA IR strongly correlated with the clamp IR in type 2 diabetic patients treated with SUs as well as in those treated with diet alone.
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The AMP-activated protein kinase (AMPK) is a ubiquitous mammalian protein kinase important in the adaptation of cells to metabolic stress. The enzyme is a heterotrimer, consisting of a catalytic alpha subunit and regulatory beta and gamma subunits, each of which is a member of a larger isoform family. The enzyme is allosterically regulated by AMP and by phosphorylation of the alpha subunit. The beta subunit is post-translationally modified by myristoylation and multi-site phosphorylation. In the present study, we have examined the impact of post-translational modification of the beta-1 subunit on enzyme activity, heterotrimer assembly and subcellular localization, using site-directed mutagenesis and expression of subunits in mammalian cells. Removal of the myristoylation site (G2A mutant) results in a 4-fold activation of the enzyme and relocalization of the beta subunit from a particulate extranuclear distribution to a more homogenous cell distribution. Mutation of the serine-108 phosphorylation site to alanine is associated with enzyme inhibition, but no change in cell localization. In contrast, the phosphorylation site mutations, SS24, 25AA and S182A, while having no effects on enzyme activity, are associated with nuclear redistribution of the subunit. Taken together, these results indicate that both myristoylation and phosphorylation of the beta subunit of AMPK modulate enzyme activity and subunit cellular localization, increasing the complexity of AMPK regulation.
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To investigate the efficacy of the intake of vinegar for prevention of hyperlipidaemia, we examined the effect of dietary acetic acid, the main component of vinegar, on serum lipid values in rats fed a diet containing 1 % (w/w) cholesterol. Animals were allowed free access to a diet containing no cholesterol, a diet containing 1 % cholesterol without acetic acid, or a diet containing 1 % cholesterol with 0.3 % (w/w) acetic acid for 19 d. Then, they were killed after food deprivation for 7 h. Cholesterol feeding increased serum total cholesterol and triacylglycerol levels. Compared with the cholesterol-fed group, the cholesterol and acetic acid-fed group had significantly lower values for serum total cholesterol and triacylglycerols, liver ATP citrate lyase (ATP-CL) activity, and liver 3-hydroxy-3-methylglutaryl-CoA content as well as liver mRNA levels of sterol regulatory element binding protein-1, ATP-CL and fatty acid synthase (P<0.05). Further, the serum secretin level, liver acyl-CoA oxidase expression, and faecal bile acid content were significantly higher in the cholesterol and acetic acid-fed group than in the cholesterol-fed group (P<0.05). However, acetic acid feeding affected neither the mRNA level nor activity of cholesterol 7alpha-hydroxylase. In conclusion, dietary acetic acid reduced serum total cholesterol and triacylglycerol: first due to the inhibition of lipogenesis in liver; second due to the increment in faecal bile acid excretion in rats fed a diet containing cholesterol.
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To investigate the anti-obesity effects of the pomegranate leaf extract (PLE) in a mouse model of high-fat diet induced obesity and hyperlipidemia. For the anti-obesity experiment, male and female ICR mice were fed with a high-fat diet to induce obesity. When the weight of the high-fat diet group was 20% higher than the normal diet group, the animals were treated with 400 or 800 mg/kg/day of PLE for 5 weeks. Body weight and daily food intake were measured regularly during the experimental period. The various adipose pads were weighed and serum total cholesterol (TC), triglyceride (TG), glucose and high-density lipoprotein cholesterol (HDL-C) were measured after 5 weeks, treatment with PLE. In the fat absorption experiment, both the normal and obese mice were given 0.5 ml lipid emulsion and PLE at a dose of 800 mg/kg at the same time. Serial serum TG levels were measured at times 1, 2, 3, 4 and 6 h after the treatment. TGs in fecal excretions were measured after the mice were orally given a lipid emulsion. Effects of PLE and its isolated compounds (ellagic acid and tannic acid) on pancreatic lipase activity were examined in vitro. The PLE-treated groups showed a significant decrease in body weight, energy intake and various adipose pad weight percents and serum, TC, TG, glucose levels and TC/HDL-C ratio after 5 weeks treatment. Furthermore, PLE significantly attenuated the raising of the serum TG level and inhibited the intestinal fat absorption in mice given a fat emulsion orally. PLE showed a significant difference in decreasing the appetite of obese mice fed a high-fat diet, but showed no effect in mice fed a normal diet. PLE can inhibit the development of obesity and hyperlipidemia in high-fat diet induced obese mice. The effects appear to be partly mediated by inhibiting the pancreatic lipase activity and suppressing energy intake. PLE may be a novel appetite suppressant that only affects obesity owing to a high-fat diet.
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Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative C(T) method also referred to as the 2 (-DeltaDeltaC(T)) method. This protocol provides an overview of the comparative C(T) method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.
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Two different methods of presenting quantitative gene expression exist: absolute and relative quantification. Absolute quantification calculates the copy number of the gene usually by relating the PCR signal to a standard curve. Relative gene expression presents the data of the gene of interest relative to some calibrator or internal control gene. A widely used method to present relative gene expression is the comparative CT method also referred to as the 2−ΔΔCT method. This protocol provides an overview of the comparative CT method for quantitative gene expression studies. Also presented here are various examples to present quantitative gene expression data using this method.
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Resistin, an adipocytokine, is considered the link between obesity and type 2 diabetes. Pomegranate is a rich source of compounds used to treat metabolic diseases including type 2 diabetes. In this study, we found that consumption of pomegranate fruit extract (PFE) predominantly reduced the serum resistin levels in ovariectomized mice, an animal model with elevated resistin levels in serum and upregulated resistin mRNA expression in white adipose tissue. Moreover, the PFE significantly reduced the secretion and intracellular protein levels of resistin in differentiated murine 3T3-L1 adipocytes, but it did not alter resistin mRNA expression. When de novo protein synthesis was inhibited by the protein synthesis inhibitor cycloheximide, the intracellular resistin protein levels were drastically reduced by the PFE, suggesting that the PFE promoted the degradation of resistin at the protein level. We also found that ellagic acid (EA), a main component of pomegranate, had the same effects on the secretion and intracellular protein level of resistin. These results suggest that EA in pomegranate suppresses resistin secretion by a novel mechanism involving the degradation of intracellular resistin protein in adipocytes.
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Drinking an herbal tea to lose weight is a well-liked concept. This study was designed to examine the possible improvement of obesity phenotype by a new tea represented by its purified components, gallic acid, ellagic acid, and rubusoside (GER). Male obese-prone SD rats were given low-fat diet, high-fat diet, or high-fat diet plus GER at the dose of 0.22 g/kg of body weight for 9 weeks. GER significantly reduced body weight gain by 22% compared to the high-fat diet control group with 48% less abdominal fat gain. Food intake was not affected. Blood glucose was lowered in the GER-treated group, whereas serum triglycerides and cholesterol were significantly reduced by 50%. This improved obesity phenotype may be associated with the attenuated expression of vascular endothelial growth factor in preadipocyte 3T3-L1 cells. Although other underlying, possibly multiple, mechanisms behind the improved phenotype are largely unknown, the observed improvement of multiple obesity-related parameters by the new tea warrants further investigations.
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Acetic acid (AcOH), a main component of vinegar, recently was found to suppress body fat accumulation in animal studies. Hence we investigated the effects of vinegar intake on the reduction of body fat mass in obese Japanese in a double-blind trial. The subjects were randomly assigned to three groups of similar body weight, body mass index (BMI), and waist circumference. During the 12-week treatment period, the subjects in each group ingested 500 ml daily of a beverage containing either 15 ml of vinegar (750 mg AcOH), 30 ml of vinegar (1,500 mg AcOH), or 0 ml of vinegar (0 mg AcOH, placebo). Body weight, BMI, visceral fat area, waist circumference, and serum triglyceride levels were significantly lower in both vinegar intake groups than in the placebo group. In conclusion, daily intake of vinegar might be useful in the prevention of metabolic syndrome by reducing obesity.
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Two types of adipose tissue can be distinguished histologically and functionally: white (WAT) and brown adipose tissue (BAT). Whereas BAT is specialized in the production of heat, WAT stores excess energy as triacylglycerols. BAT is present throughout life in rodents, whereas in humans it was thought to involute rapidly postnatally, having essentially disappeared within the first years after birth. However, positron emission tomography has provided evidence that adults retain metabolically active BAT depots that can be induced in response to cold and sympathetic nervous system activation. These findings together with the recent identification of specific molecular determinants (PRDM16 and BMP7) activating brown adipogenesis highlights BAT as a potential relevant target for pharmacological and gene expression manipulation to combat human obesity.
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We investigated the effect of acetic acid (AcOH) on the prevention of obesity in high-fat-fed mice. The mice were intragastrically administrated with water or 0.3 or 1.5% AcOH for 6 weeks. AcOH administration inhibited the accumulation of body fat and hepatic lipids without changing food consumption or skeletal muscle weight. Significant increases were observed in the expressions of genes for peroxisome-proliferator-activated receptor alpha (PPARalpha) and for fatty-acid-oxidation- and thermogenesis-related proteins: acetyl-CoA oxidase (ACO), carnitine palmitoyl transferase-1 (CPT-1), and uncoupling protein-2 (UCP-2), in the liver of the AcOH-treatment groups. PPARalpha, ACO, CPT-1, and UCP-2 gene expressions were increased in vitro by acetate addition to HepG2 cells. However, the effects were not observed in cells depleted of alpha2 5'-AMP-activated protein kinase (AMPK) by siRNA. In conclusion, AcOH suppresses accumulation of body fat and liver lipids by upregulation of genes for PPARalpha and fatty-acid-oxidation-related proteins by alpha2 AMPK mediation in the liver.
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Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.
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The assimilation, storage and use of energy from nutrients constitute a homeostatic system that is essential for life. In vertebrates, the ability to store sufficient quantities of energy-dense triglyceride in adipose tissue allows survival during the frequent periods of food deprivation encountered during evolution. However, the presence of excess adipose tissue can be maladaptive. A complex physiological system has evolved to regulate fuel stores and energy balance at an optimum level. Leptin, a hormone secreted by adipose tissue, and its receptor are integral components of this system. Leptin also signals nutritional status to several other physiological systems and modulates their function. Here we review the role of leptin in the control of body weight and its relevance to the pathogenesis of obesity.
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The cloning of the ob gene and its gene product, leptin, has led to the elucidation of a robust physiologic system that maintains fat stores at a relatively constant level. Leptin is a peptide hormone secreted by adipose tissue in proportion to its mass. Recessive mutations in the leptin gene are associated with massive obesity in mice and humans, establishing a genetic basis for obesity. Leptin circulates in blood and acts on the brain to regulate food intake and energy expenditure. When fat mass falls, plasma leptin levels fall, stimulating appetite and suppressing energy expenditure until fat mass is restored. When fat mass increases, leptin levels increase, suppressing appetite until weight is lost. This system maintains homeostatic control of adipose tissue mass. The discovery of leptin has advanced our understanding of metabolic disease in a number of respects. Its identification has revealed a new endocrine system regulating body weight. This system provides a means by which changes in nutritional state regulate other physiologic systems. A number of leptin deficiency syndromes that are treatable with leptin replacement have been identified. The majority of obese subjects are leptin resistant, which establishes that obesity is the result of hormone resistance. Leptin treatment results in weight loss in a subset of obese patients and can also synergize with other anti-obesity agents to reduce weight in the general population. Leptin provides an entry point for studying a complex human behavior. Finally, this research has established that there is a powerful biological basis for obesity, a fact that is (correctly) changing public perception about the pathogenesis of this medical condition.
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All cells must maintain a high ratio of cellular ATP:ADP to survive. Because of the adenylate kinase reaction (2ADP <--> ATP + AMP), AMP rises whenever the ATP:ADP ratio falls, and a high cellular ratio of AMP:ATP is a signal that the energy status of the cell is compromised. The AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that is switched on by a rise in the AMP:ATP ratio, via a complex mechanism that results in an exquisitely sensitive system. AMPK is switched on by cellular stresses that either interfere with ATP production (e.g. hypoxia, glucose deprivation, or ischemia) or by stresses that increase ATP consumption (e.g. muscle contraction). It is also activated by hormones that act via Gq-coupled receptors, and by leptin and adiponectin, via mechanisms that remain unclear. Once activated, the system switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes that are not essential for short-term cell survival, such as the synthesis of lipids, carbohydrates, and proteins. The AMPK cascade is the probable target for the antidiabetic drug metformin, and current indications are that it is responsible for many of the beneficial effects of exercise in the treatment and prevention of type 2 diabetes and the metabolic syndrome.
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The metabolic syndrome is a common metabolic disorder that results from the increasing prevalence of obesity. The disorder is defined in various ways, but in the near future a new definition(s) will be applicable worldwide. The pathophysiology seems to be largely attributable to insulin resistance with excessive flux of fatty acids implicated. A proinflammatory state probably contributes to the syndrome. The increased risk for type 2 diabetes and cardiovascular disease demands therapeutic attention for those at high risk. The fundamental approach is weight reduction and increased physical activity; however, drug treatment could be appropriate for diabetes and cardiovascular disease risk reduction.
Article
Acetic acid (AcOH), which is a short-chain fatty acid, is reported to have some beneficial effects on metabolism. To test the hypothesis that feeding of AcOH exerts beneficial effects on glucose homeostasis in type 2 diabetes, we fed either a standard diet or one containing 0.3% AcOH to KK-A(y) mice for 8 weeks. Fasting plasma glucose and HbA1c levels were lower in mice fed AcOH for 8 weeks than in control mice. AcOH also reduced the expression of genes involved in gluconeogenesis and lipogenesis, which is in part regulated by 5'-AMP-activated protein kinase (AMPK) in the liver. Finally, sodium acetate, in the form of neutralized AcOH, directly activated AMPK and lowered the expression of genes such as for glucose-6-phosphatase and sterol regulatory element binding protein-1 in rat hepatocytes. These results indicate that the hypoglycemic effect of AcOH might be due to activation of AMPK in the liver.
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