Insights into the molecular mechanisms of the anti-atherogenic actions of flavonoids in normal and obese mice.
Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state.
Department of Plant Biology and Pathology, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, United States of America.
Elena V
EV
Shabrova
Olga
O
Tarnopolsky
Ajay P
AP
Singh
Jorge
J
Plutzky
Nicholi
N
Vorsa
Loredana
L
Quadro
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006262:Health; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D029799:Vaccinium macrocarpon / Q000737:chemistry
D052242:Adiponectin; D001786:Blood Glucose; D005419:Flavonoids; D054419:Receptors, Adiponectin; D002784:Cholesterol; D055372:AMP-Activated Protein Kinases