Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism.
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.
Cederroth
Christopher R
CR
Department of Genetic Medicine and Development, National Centre of Competence in Research-Frontiers in Genetics, University of Geneva, 1211 Geneva 4, Switzerland.
Vinciguerra
Manlio
M
Gjinovci
Asllan
A
Kühne
Françoise
F
Klein
Marcella
M
Cederroth
Manon
M
Caille
Dorothée
D
Suter
Mariane
M
Neumann
Dietbert
D
James
Richard W
RW
Doerge
Daniel R
DR
Wallimann
Theo
T
Meda
Paolo
P
Foti
Michelangelo
M
Rohner-Jeanrenaud
Françoise
F
Vassalli
Jean-Dominique
JD
Nef
Serge
S
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
D001786:Blood Glucose; D007328:Insulin; D007529:Isoflavones; D008055:Lipids; D009097:Multienzyme Complexes; D048789:Phytoestrogens; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases