Dietary Phytoestrogens Activate AMP-Activated Protein Kinase With Improvement in Lipid and Glucose Metabolism

  1. Christopher R. Cederroth1,
  2. Manlio Vinciguerra2,
  3. Asllan Gjinovci2,
  4. Françoise Kühne1,
  5. Marcella Klein3,
  6. Manon Cederroth1,
  7. Dorothée Caille2,
  8. Mariane Suter4,
  9. Dietbert Neumann4,
  10. Richard W. James5,
  11. Daniel R. Doerge6,
  12. Theo Wallimann4,
  13. Paolo Meda2,
  14. Michelangelo Foti2,
  15. Françoise Rohner-Jeanrenaud3,
  16. Jean-Dominique Vassalli1 and
  17. Serge Nef1
  1. 1Department of Genetic Medicine and Development and National Centre of Competence in Research–Frontiers in Genetics, University of Geneva, Geneva, Switzerland
  2. 2Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland
  3. 3Laboratory of Metabolism, University of Geneva, Geneva, Switzerland
  4. 4Institute of Cell Biology, ETH Zürich, Zürich, Switzerland
  5. 5Clinical Diabetes Unit, Division of Endocrinology, Diabetology, and Nutrition, Faculty of Medicine, Department of Internal Medicine, University of Geneva, Geneva, Switzerland
  6. 6National Center for Toxicological Research, Jefferson, Arkansas
  1. Corresponding author: Serge Nef, Department of Genetic Medicine and Development and National Centre of Competence in Research–Frontiers in Genetics, University of Geneva, 1211 Geneva 4, Switzerland. E-mail: serge.nef{at}


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.

RESEARCH DESIGN AND 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.


  • Published ahead of print at on day month year. DOI: 10.2337/db07-0630.

    Additional information for this article can be found in an online appendix at

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted January 31, 2008.
    • Received May 10, 2007.
| Table of Contents

This Article

  1. Diabetes vol. 57 no. 5 1176-1185
  1. Online-Only Appendix
  2. All Versions of this Article:
    1. db07-0630v1
    2. 57/5/1176 most recent