Leixuri Aguirre

Resveratrol: Anti-Obesity Mechanisms of Action

Resveratrol is a non-flavonoid polyphenol which belongs to the stilbenes group and is produced naturally in several plants in response to injury or fungal attack. Resveratrol has been recently reported as preventing obesity. The present review aims to compile the evidence concerning the potential mechanisms of action which underlie the anti-obesity effects of resveratrol, obtained either in cultured cells lines and animal models. Published studies demonstrate that resveratrol has an anti-adipogenic effect. A good consensus concerning the involvement of a down-regulation of C/EBPα and PPARγ in this effect has been reached. Also, in vitro studies have demonstrated that resveratrol can increase apoptosis in mature adipocytes. Furthermore, different metabolic pathways involved in triacylglycerol metabolism in white adipose tissue have been shown to be targets for resveratrol. Both the inhibition of de novo lipogenesis and adipose tissue fatty acid uptake mediated by lipoprotein lipase play a role in explaining the reduction in body fat which resveratrol induces. As far as lipolysis is concerned, although this compound per se seems to be unable to induce lipolysis, it increases lipid mobilization stimulated by β-adrenergic agents. The increase in brown adipose tissue thermogenesis, and consequently the associated energy dissipation, can contribute to explaining the body-fat lowering effect of resveratrol. In addition to its effects on adipose tissue, resveratrol can also acts on other organs and tissues. Thus, it increases mitochondriogenesis and consequently fatty acid oxidation in skeletal muscle and liver. This effect can also contribute to the body-fat lowering effect of this molecule.

Beneficial Effects of Quercetin on Obesity and Diabetes

Scientific research is constantly looking for new molecules that could be used as dietary functional ingredients in the fight against obesity and diabetes, two pathologies highly prevalent in Western societies. In this context, flavonoids represent a group of molecules of increasing interest. The major flavonoid is Quercetin, which belongs to the class called flavonols and is mainly found in apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. It exhibits a wide range of biological functions including anticarcenogenic, anti-inflammatory and antiviral; it also inhibits lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the main effects of Quercetin on obesity and diabetes. The mechanisms of action explaining the effects of Quercetin on these two metabolic disturbances are also considered. Good perspectives have been opened for Quercetin, according to the results obtained either in cell cultures or in animal models. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of this flavonoid on these pathologies. Moreover, the body fat-lowering effect and the improvement of glucose homeostasis need to be confirmed in humans. Animal studies have consistently failed to demonstrate adverse effects caused by Quercetin. In contrast, due to inhibitory effect of Quercetin in cytochrome P450, interactions with drugs can be taken into account when they are administered at the same time than Quercetin.

Effects of resveratrol and other polyphenols in hepatic steatosis.

Non-alcoholic fatty liver disease covers a wide spectrum of liver pathologies which range from simple steatosis to non-alcoholic steatohepatitis. Polyphenols are members of a very large family of plant-derived compounds that can have beneficial effects on human health, and thus their study has become an increasingly important area of human nutrition research. The aim of the present review is to compile published data concerning the effects of both isolated polyphenols as well as polyphenol extracts, on hepatocyte and liver fat accumulation under different steatosis-inducing conditions. The results reported clearly show that this group of biomolecules is able to reduce fat accumulation, but further studies are needed to establish the optimal dose and treatment period length. With regard to the potential mechanisms of action, there is a good consensus. The anti-lipidogenic effect of polyphenols is mainly due to reduced fatty acid and triacylglycerol synthesis, increased in fatty acid oxidation, and reduced of oxidative stress and inflammation. As a general conclusion, it can be stated that polyphenols are biomolecules which produce hepatoprotective effects. To date, these beneficial effects have been demonstrated in cultured cells and animal models. Thus, studies performed in humans are needed before these molecules can be considered as truly useful tools in the prevention of liver steatosis.

Pterostilbene, a Dimethyl Ether Derivative of Resveratrol, Reduces Fat Accumulation in Rats Fed an Obesogenic Diet

The current study aimed to demonstrate the effects of pterostilbene in rats fed an obesogenic diet. For this purpose, pterostilbene was administered at doses of 15 mg/kg body weight/day (PT15 group) or 30 mg/kg body weight/day (PT30 group) for 6 weeks. Pterostilbene reduced adipose tissue mass -15.1% (PT15) and -22.9% (PT30). In this tissue, it decreased malic enzyme (-39.4 and -49.5% for PT15 and PT30 groups, respectively) and fatty acid synthase (-45 and -53.4% for PT15 and PT30) activities. Acetyl-CoA carboxylase activity was reduced and AMPK activity was increased only in the PT30 group. In the liver, pterostilbene (PT30) reduced malic enzyme (-29.5%) and glucose-6-P dehydrogenase (-43.2%) activities and increased carnitine palmitoyltransferase-1a (37.5%) and acyl-coenzyme A oxidase (42.5%) activities. This increased oxidative capacity was not associated with increased mitochondriogenesis. Among biochemical serum parameters, only insulin was modified by pterostilbene (-31.6%) in the PT15 group. The amounts of pterostilbene in serum and tissues from rats in the PT30 group were in not all cases 2-fold greater than those found in the PT15 group. In conclusion, pterostilbene shows antiobesity properties due, at least in part, to reduced lipogenesis in adipose tissue and increased fatty acid oxidation in liver.

Pterostilbene-induced changes in gut microbiota composition in relation to obesity.

SCOPE Nutritional interventions based on the use of natural bioactive compounds might offer new possibilities for reshaping obesity-associated bacterial dysregulation or dysbiosis and improving health. We evaluated whether pterostilbene supplementation could induce changes in gut microbiota composition and whether these modifications were associated with improvements in metabolic variables. METHODS AND RESULTS Zucker (fa/fa) rats were given a standard diet supplemented (n = 10) or not (n = 9) with pterostilbene (15 mg/kg body weight/day) by oral gavage for 6 weeks. Faucal samples at the beginning and at the end of the intervention period were analyzed by Illumina Mi-Seq sequencing approach. Pterostilbene exerted protective antiobesity effects, improved metabolic function (insulin sensitivity), and induced structural changes in gut microbiota composition. A decrease in the levels of Firmicutes and an increase in Verrucomicrobia phyla were detected in the pterostilbene-treated group. Bacterial species belonging to genera Akkermansia and Odoribacter were also increased. A strong inverse correlation between Akkermansia muciniphila and body weight was evidenced. Odoribacter splanchnicus showed a negative correlation with adiposity. CONCLUSION Pterostilbene modifies intestinal bacteria composition toward a healthier microbial profile and suggests that the antiobesity effects induced in Zucker rats could be associated with an enrichment of the mucin-degrading bacterial members, namely Akkermansia and Odoribacter genus.

Effects of pomegranate seed oil on glucose and lipid metabolism-related organs in rats fed an obesogenic diet.

Studies conducted in mice have revealed positive effects of punicic acid (PUA). The aim of this study was to analyze the effects of PUA on fat accumulation and glycemic control in rats fed an obesogenic diet. Rats were randomly divided into two groups: control group and PUA group (diet supplemented with 0.5% PUA). No changes were observed in adipose tissue weights. The glucose tolerance test showed that the glycemic value in the PUA group had decreased significantly at the final time (120 min) (-19.3%), as had fructosamine levels (-11.1%). However, homeostasis model assessment (HOMA-IR) showed that insulin resistance did not improve. No changes were observed in the liver, skeletal muscle composition, or peroxisome proliferator-activated receptors (PPARs) activation. Low levels (mg/g tissue) of PUA (0.04 ± 0.01 in both tissues) and higher levels of cis-9,trans-11 conjugated linoleic acid (0.31 ± 0.08 in liver, 0.52 ± 0.11 in muscle) were found. PUA supplementation induced hypoplasia (-16.1%) due to the antiproliferative effect on hepatocytes. In conclusion, dietary supplementation of 0.5% PUA did not lead to decreased fat accumulation in adipose tissue, liver, or skeletal muscle, or to improved glycemic control. The hypoplasia induced in liver is a negative effect that should be considered before proposing PUA as a functional ingredient.

Anti-obesity effects of resveratrol: comparison between animal models and humans

The prevalence of obesity has increased rapidly during recent years and has reached epidemic proportions. As a result, the scientific community is interested in active biomolecules which are naturally present in plants and foodstuffs and may be useful in body weight management. In recent years, polyphenols have made up one of the most frequently studied groups among these molecules. Numerous studies have been carried out on animals to analyse the potential anti-obesity effects of resveratrol, a non-flavonoid polyphenol, and a general consensus concerning the body-fat-lowering effect of this compound exists. By contrast, studies in humans have been few so far. Moreover, in these studies, the effectiveness of resveratrol is low. The aims of the present review are to summarize the results reported so far on this topic and to justify the differences observed between animals and humans. It seems that the reduced response to resveratrol in humans cannot be attributed to the use of lower doses in humans because the doses that induce body-fat-lowering effects in rodents are in the same range as those used in human studies. With regard to the experimental period length, treatments were longer in animal studies than in human studies. This can be one of the reasons contributing to the reduced responses observed in humans. Moreover, animals used in the reported studies are young while volunteers participating in human studies are adults, suggesting that resveratrol may be more efficient in young individuals. In addition to differences in the experimental designs, metabolic differences between animals and human cannot be discarded.

MicroRNAs involved in the browning process of adipocytes

The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19–22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA) that miR-196a, miR-26 and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b and miR-34 act as negative regulators of this process. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation.The present review focuses on the role of miRNAs in the control of white adipose tissue browning, a process which describes the recruitment of adipocytes showing features of brown adipocytes in white adipose tissue. MicroRNAs (miRNAs) are a class of short non-coding RNAs (19–22 nucleotides) involved in gene regulation. Although the main effect of miRNAs is the inhibition of the translational machinery, thereby preventing the production of the protein product, the activation of protein translation has also been described in the literature. In addition to modifying translation, miRNAs binding to its target mRNAs also trigger the recruitment and association of mRNA decay factors, leading to mRNA destabilization, degradation, and thus to the decrease in expression levels. Although a great number of miRNAs have been reported to potentially regulate genes that play important roles in the browning process, only a reduced number of studies have demonstrated experimentally an effect on this process associated to changes in miRNA expressions, so far. These studies have shown, by using either primary adipocyte cultures or experimental models of mice (KO mice, mice overexpressing a specific miRNA) that miR-196a, miR-26 and miR-30 are needed for browning process development. By contrast, miR-155, miR-133, miR-27b and miR-34 act as negative regulators of this process. Further studies are needed to fully describe the miRNA network-involved white adipose tissue browning regulation.

Novel equation to determine the hepatic triglyceride concentration in humans by MRI: diagnosis and monitoring of NAFLD in obese patients before and after bariatric surgery.

BackgroundNon-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since NAFLD is usually asymptomatic at diagnosis, new non-invasive approaches are needed to determine the hepatic lipid content in terms of diagnosis, treatment and control of disease progression. Here, we investigated the potential of magnetic resonance imaging (MRI) to quantitate and monitor the hepatic triglyceride concentration in humans.MethodsA prospective study of diagnostic accuracy was conducted among 129 consecutive adult patients (97 obesity and 32 non-obese) to compare multi-echo MRI fat fraction, grade of steatosis estimated by histopathology, and biochemical measurement of hepatic triglyceride concentration (that is, Folch value).ResultsMRI fat fraction positively correlates with the grade of steatosis estimated on a 0 to 3 scale by histopathology. However, this correlation value was stronger when MRI fat fraction was linked to the Folch value, resulting in a novel equation to predict the hepatic triglyceride concentration (mg of triglycerides/g of liver tissue = 5.082 + (432.104 * multi-echo MRI fat fraction)). Validation of this formula in 31 additional patients (24 obese and 7 controls) resulted in robust correlation between the measured and estimated Folch values. Multivariate analysis showed that none of the variables investigated improves the Folch prediction capacity of the equation. Obese patients show increased steatosis compared to controls using MRI fat fraction and Folch value. Bariatric surgery improved MRI fat fraction values and the Folch value estimated in obese patients one year after surgery.ConclusionsMulti-echo MRI is an accurate approach to determine the hepatic lipid concentration by using our novel equation, representing an economic non-invasive method to diagnose and monitor steatosis in humans.

Comparative effects of energy restriction and resveratrol intake on glycemic control improvement

Resveratrol (RSV) has been proposed as an energy restriction mimetic. This study aimed to compare the effects of RSV and energy restriction on insulin resistance induced by an obesogenic diet. Any additive effect of both treatments was also analyzed. Rats were fed a high-fat high-sucrose diet for 6 weeks. They were then distributed in four experimental groups which were either fed a standard control diet (C), or treated with RSV (30 mg/kg/d), or submitted to energy restriction (R, 15%), or treated with RSV and submitted to energy restriction (RR). A glucose tolerance test was performed, and serum glucose, insulin, fructosamine, adiponectin, and leptin concentrations determined. Muscle triacylglycerol content and protein expression of insulin receptor (IRβ), protein kinase B (Akt), Akt substrate of 160 kDa (AS160) and glucose transporter 4 (GLUT-4) were measured. In RSV rats, fructosamine concentrations were reduced, HOMA-IR remained unchanged, but glucose tolerance was improved, without changes in phosphorylation of IRβ, Akt, and AS160 or in GLUT-4 protein expression. Rats under energy restriction showed an improvement in all the markers related to glycemic control, as well as increased phosphorylation of AS160 and protein expression of GLUT-4. In rats from RR group the results were similar to R group, with the exception of IRβ and Akt phosphorylation, which were increased. In conclusion, mild energy restriction is more efficient than intake of RSV within a standard balanced diet, and acts by means of a different mechanism from that of RSV. No additive effects between RSV and energy restriction were observed.