Glucuronide metabolites of trans-ε-viniferin decrease triglycerides accumulation in an in vitro model of hepatic steatosis.

Trans-ε-viniferin, a resveratrol dimer found mainly in grapevine wood, has shown protective capacities against hepatic steatosis in vivo. Nevertheless, this compound is very poorly bioavailable. Thus, the aim of the present study is to determine the potential anti-steatotic properties of 1 and 10 µM of trans-ε-viniferin and its four glucuronide metabolites in AML-12 cells treated with palmitic acid as an in vitro model of hepatic steatosis. The effect of the molecules in cell viability and triglyceride accumulation, and the underlying mechanisms of action by Real-Time PCR and Western Blot were analysed, as well as the quantification of trans-ε-viniferin and the identified bioactive metabolite inside cells and their incubation media. Interestingly, we were able to determine the triglyceride-lowering property of one of the glucuronides (trans-ε-viniferin-2-glucuronide), which acts on de novo lipogenesis, fatty acid uptake and triglyceride assembly. The glucuronides of trans-ε-viniferin would therefore be partly responsible for the in vivo observed anti-steatotic properties of the parent compound.

In Vitro Screening and Lipid-Lowering Effect of Prickly Pear (Opuntia Ficus-Indica L. Mill.) Fruit Extracts in 3T3-L1 Pre-Adipocytes and Mature Adipocytes.

Opuntia ficus-indica fruits have been widely used due to their nutritional composition and beneficial effects on health, particularly against chronic diseases such as diabetes, obesity, cardiovascular diseases and cancer, among others. In recent years, prickly pear peel and pulp extracts have been characterised, and a high number of bioactive compounds have been identified. This study aimed to analyse the triglyceride-lowering effect of prickly pear peel and pulp extracts obtained from fruits of three varieties (Pelota, Sanguinos, and Colorada) in 3T3-L1 maturing and mature adipocytes. At a concentration of 50 µg/mL, peel extracts from Colorada reduced triglyceride accumulation in pre-adipocytes and mature adipocytes. Additionally, at 25 µg/mL, Pelota peel extract decreased triglyceride content in mature adipocytes. Moreover, maturing pre-adipocytes treated with 50 and 25 µg/mL of Sanguinos pulp extract showed a reduction of triglyceride accumulation. In addition, the lipid-lowering effect of the main individual betalain and phenolic compounds standards were assayed. Piscidic acid and isorhamnetin glycoside (IG2), found in Colorada peel extract, were identified as the bioactive compounds that could contribute more notably to the triglyceride-lowering effect of the extract. Thus, the betalain and phenolic-rich extracts from Opuntia ficus indica fruits may serve as an effective tool in obesity management.

Effects of Physiological Doses of Resveratrol and Quercetin on Glucose Metabolism in Primary Myotubes.

Phenolic compounds have emerged in recent years as an option to face insulin resistance and diabetes. The central aim of this study was: (1) to demonstrate that physiological doses of resveratrol (RSV) or quercetin (Q) can influence glucose metabolism in human myotubes, (2) to establish whether AMP-activated protein kinase (AMPK) and protein kinase B -PKB- (Akt) pathways are involved in this effect. In addition, the effects of these polyphenols on mitochondrial biogenesis and fatty acid oxidation were analysed. Myotubes from healthy donors were cultured for 24 h with either 0.1 µM of RSV or with 10 µM of Q. Glucose metabolism, such as glycogen synthesis, glucose oxidation, and lactate production, were measured with D[U-14C]glucose. ß-oxidation using [1-14C]palmitate as well as the expression of key metabolic genes and proteins by Real Time PCR and Western blot were also assessed. Although RSV and Q increased pgc1α expression, they did not significantly change either glucose oxidation or ß-oxidation. Q increased AMPK, insulin receptor substrate 1 (IRS-1), and AS160 phosphorylation in basal conditions and glycogen synthase kinase 3 (GSK3ß) in insulin-stimulated conditions. RSV tended to increase the phosphorylation rates of AMPK and GSK3ß. Both of the polyphenols increased insulin-stimulated glycogen synthesis and reduced lactate production in human myotubes. Thus, physiological doses of RSV or Q may exhibit anti-diabetic actions in human myotubes.

Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health.

Isoflavones are phenolic compounds with a chemical structure similar to that of estradiol. They are present in several vegetables, mainly in legumes such as soy, white and red clover, alfalfa and beans. The most significant food source of isoflavones in humans is soy-derived products. Isoflavones could be used as an alternative therapy for pathologies dependent on hormonal disorders such as breast and prostate cancer, cardiovascular diseases, as well as to minimize menopausal symptoms. According to the results gathered in the present review, it can be stated that there is scientific evidence showing the beneficial effect of isoflavones on bone health and thus in the prevention and treatment of osteoporosis on postmenopausal women, although the results do not seem entirely conclusive as there are discrepancies among the studies, probably related to their experimental designs. For this reason, the results should be interpreted with caution, and more randomized clinical trials are required. By contrast, it seems that soy isoflavones do not lead to a meaningful protective effect on cardiovascular risk. Regarding cancer, scientific evidence suggests that isoflavones could be useful in reducing the risk of suffering some types of cancer, such as breast and endometrial cancer, but further studies are needed to confirm these results. Finally, isoflavones could be useful in reducing hot flushes associated with menopause. However, a limitation in this field is that there is still a great heterogeneity among studies. Lastly, with regard to isoflavone consumption safety, it seems that they are safe and that the most common adverse effect is mild and occurs at the gastrointestinal level.

Anti-Obesity Effects of Microalgae.

In recent years, microalgae have attracted great interest for their potential applications in nutraceutical and pharmaceutical industry as an interesting source of bioactive medicinal products and food ingredients with anti-oxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. One potential application for bioactive microalgae compounds is obesity treatment. This review gathers together in vitro and in vivo studies which address the anti-obesity effects of microalgae extracts. The scientific literature supplies evidence supporting an anti-obesity effect of several microalgae: Euglena gracilis, Phaeodactylum tricornutum, Spirulina maxima, Spirulina platensis, or Nitzschia laevis. Regarding the mechanisms of action, microalgae can inhibit pre-adipocyte differentiation and reduce de novo lipogenesis and triglyceride (TG) assembly, thus limiting TG accumulation. Increased lipolysis and fatty acid oxidation can also be observed. Finally, microalgae can induce increased energy expenditure via thermogenesis activation in brown adipose tissue, and browning in white adipose tissue. Along with the reduction in body fat accumulation, other hallmarks of individuals with obesity, such as enhanced plasma lipid levels, insulin resistance, diabetes, or systemic low-grade inflammation are also improved by microalgae treatment. Not only the anti-obesity effect of microalgae but also the improvement of several comorbidities, previously observed in preclinical studies, has been confirmed in clinical trials.

Delipidating effect of resveratrol metabolites in 3T3-L1 adipocytes.

SCOPE: Due to the low bioavailability of resveratrol, determining whether its metabolites exert any beneficial effect is an interesting issue. METHODS AND RESULTS: 3T3-L1 maturing pre-adipocytes were treated from day 0 to day 8 of differentiation and mature adipocytes for 24 h on day 12 with 1, 10, or 25 µM of resveratrol or its metabolites. Triacylglycerols were assessed by spectrophotometry and gene expression by real time RT-PCR. Resveratrol, trans-resveratrol-4'-O-glucuronide and trans-resveratrol-3-O-sulfate reduced triacylglycerol content in maturing pre-adipocytes at 25 µM. In mature adipocytes, both resveratrol and its glucuronide metabolites, though not sulfate metabolite, reduced triacylglycerol content, although resveratrol was more effective than them. Resveratrol and the three metabolites reduced C/EBPß mRNA levels. Trans-resveratrol-3-O-sulfate also reduced C/EBP-α, peroxisome proliferator-activated receptor γ (PPAR-γ), and lipoprotein lipase (LPL) expression. In mature adipocytes, resveratrol increased ATGL, CPT-1, deacetylase sirtuin 1 (SIRT-1), and PGC1-α expression. Trans-resveratrol-3-O-glucuronide reduced mRNA levels of FASN and increased those of SIRT-1. Trans-resveratrol-4'-O-glucuronide increased HSL and SIRT-1 mRNA levels. Trans-resveratrol-3-O-sulfate did not change gene expression. CONCLUSION: The present study shows for the first time the delipidating effect of (i) resveratrol metabolites in maturing pre-adipocytes and (ii) glucuronide metabolites in mature adipocytes. This suggests that both resveratrol and resveratrol metabolites may be involved in the anti-obesity effect of this polyphenol.