3-methylquercetin and Obesity

Isorhamnetin is a plant-derived secondary metabolite which belongs to the family of flavonoids. This review summarises the main outcomes described in the literature to date, regarding the effects of isorhamnetin on obesity from in vitro and in vivo studies. The studies carried out in pre-adipocytes show that isorhamnetin is able to reduce adipogenesis at 10 μM or higher doses and that these effects are mediated by Pparγ and by Wnt signalling pathway. Very few studies addressed in rodents are available so far. It seems that treatment periods longer than two weeks are needed by isorhamnetin and its glycosides to be effective as anti-obesity agents. Nevertheless, improvements in glycaemic control can be observed even in short treatments. Regarding the underlying mechanisms of action, although some contradictory results have been found, reductions in

Topics: Adipogenesis; Animals; Anti-Obesity Agents; Glycosides; Humans; Lipogenesis; Obesity; Quercetin

Studies on peroxisome proliferator-activated receptor (PPAR)-γ ligands have been focused on agonists. However, PPARγ activation may induce obesity and nonalcoholic fatty liver disease (NAFLD), one of the most challenging medical conditions. Here, we identified that isorhamnetin, a naturally occurring compound in fruits and vegetables and the metabolite of quercetin, is a novel antagonist of PPARγ. Isorhamnetin treatment inhibited the adipocyte differentiation induced by the PPARγ agonist rosiglitazone, reduced obesity development and ameliorated hepatic steatosis induced by both high-fat diet treatment and leptin deficiency. Our results suggest that dietary supplement of isorhamnetin may be beneficial to prevent obesity and steatosis and PPARγ antagonists may be useful to treat hepatic steatosis.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Animals; Cell Differentiation; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Gene Expression Regulation; Humans; Leptin; Metabolic Diseases; Mice; Models, Molecular; Molecular Conformation; Non-alcoholic Fatty Liver Disease; Obesity; PPAR gamma; Protein Binding; Quercetin; Transcriptional Activation

A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.

Topics: Animals; Anti-Obesity Agents; Diet, High-Fat; Dietary Supplements; Energy Metabolism; Gene Expression Regulation; Glucose Transporter Type 2; Glycosides; Hyperglycemia; Hyperlipidemias; Insulin; Insulin Secretion; Islets of Langerhans; Male; Mice, Inbred C57BL; Obesity; Opuntia; Plant Extracts; Plant Stems; PPAR gamma; Quercetin; Random Allocation; Rats, Wistar; Tissue Culture Techniques