title: Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism.
abstract: OBJECTIVE
  Emerging evidence suggests that dietary phytoestrogens can have beneficial effects on obesity and diabetes, although their mode of action is not known. Here, we investigate the mechanisms mediating the action of dietary phytoestrogens on lipid and glucose metabolism in rodents.
  
  
  METHODS
  Male CD-1 mice were fed from conception to adulthood with either a high soy-containing diet or a soy-free diet. Serum levels of circulating isoflavones, ghrelin, leptin, free fatty acids, triglycerides, and cholesterol were quantified. Tissue samples were analyzed by quantitative RT-PCR and Western blotting to investigate changes of gene expression and phosphorylation state of key metabolic proteins. Glucose and insulin tolerance tests and euglycemic-hyperinsulinemic clamp were used to assess changes in insulin sensitivity and glucose uptake. In addition, insulin secretion was determined by in situ pancreas perfusion.
  
  
  RESULTS
  In peripheral tissues of soy-fed mice, especially in white adipose tissue, phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase was increased, and expression of genes implicated in peroxisomal fatty acid oxidation and mitochondrial biogenesis was upregulated. Soy-fed mice also showed reduced serum insulin levels and pancreatic insulin content and improved insulin sensitivity due to increased glucose uptake into skeletal muscle. Thus, mice fed with a soy-rich diet have improved adipose and glucose metabolism.
  
  
  CONCLUSIONS
  Dietary soy could prove useful to prevent obesity and associated disorders. Activation of the AMPK pathway by dietary soy is likely involved and may mediate the beneficial effects of dietary soy in peripheral tissues.
authors.affiliation: Department of Genetic Medicine and Development, National Centre of Competence in Research-Frontiers in Genetics, University of Geneva, 1211 Geneva 4, Switzerland.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cederroth
authors.forename: Manlio
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Françoise
authors.initials: F
authors.lastname: Kühne
authors.forename: Marcella
authors.initials: M
authors.lastname: Klein
authors.forename: Manon
authors.initials: M
authors.lastname: Cederroth
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Mariane
authors.initials: M
authors.lastname: Suter
authors.forename: Dietbert
authors.initials: D
authors.lastname: Neumann
authors.forename: Richard W
authors.initials: RW
authors.lastname: James
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Foti
authors.forename: Françoise
authors.initials: F
authors.lastname: Rohner-Jeanrenaud
authors.forename: Jean-Dominique
authors.initials: JD
authors.lastname: Vassalli
authors.forename: Serge
authors.initials: S
authors.lastname: Nef
mesh_terms: D055372:AMP-Activated Protein Kinases; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003433:Crosses, Genetic; D004032:Diet; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007529:Isoflavones / Q000097:blood*; D008055:Lipids / Q000097:blood*; D008297:Male; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000502:physiology; D048789:Phytoestrogens / Q000008:administration & dosage / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D045730:Soy Foods
chemical_list: D001786:Blood Glucose; D007328:Insulin; D007529:Isoflavones; D008055:Lipids; D009097:Multienzyme Complexes; D048789:Phytoestrogens; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases