| A Phytoestrogen-Rich Diet Increases Energy Expenditure and Decreases Adiposity in Mice Christopher R. Cederroth,1 Manlio Vinciguerra,2 Françoise Kühne,1 Rime Madani,1 Daniel R. Doerge,3 Theo J. Visser,4 Michelangelo Foti,2 Françoise Rohner-Jeanrenaud,2,5 Jean-Dominique Vassalli,1 and Serge Nef1 1Department of Genetic Medicine and Development and National Center for Competence in Research - Frontiers in Genetics, and 2Department of Cellular Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland; 3National Center for Toxicological Research, Jefferson, Arkansas, USA; 4Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands; 5Department of Internal Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland Abstract
Background: Obesity is an increasingly prevalent health problem, and natural effective therapeutic approaches are required to prevent its occurrence. Phytoestrogens are plant-derived compounds with estrogenic activities ; they can bind to both estrogen receptors α and β and mimic the action of estrogens on target organs. Objectives: The purpose of this study was to examine the influence of soy-derived phytoestrogens on energy balance and metabolism. Methods: Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet from conception to adulthood. We measured circulating serum isoflavone levels using reverse-phase solid-phase extraction for subsequent liquid chromatography electrospray tandem mass spectrometry analysis. Adult animals were analyzed for body composition by dual-energy X-ray absorptiometry, locomotor activity by running-wheel experiments, respiratory exchange rate by indirect calorimetry, and food intake using metabolic cages. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine the expression of hypothalamic neuropeptide genes. Results: We found that adult mice fed a soy-rich diet had reduced body weight, adiposity, and resistance to cold. This lean phenotype was associated with an increase in lipid oxidation due to a preferential use of lipids as fuel source and an increase in locomotor activity. The modulation of energy balance was associated with a central effect of phytoestrogens on the expression of hypothalamic neuropeptides, including agouti-related protein. Conclusion: The data suggest that dietary soy could have beneficial effects on obesity, but they also emphasize the importance of monitoring the phytoestrogen content of diets as a parameter of variability in animal experiments. Key words: AgRP, endocrine disruptors, isoflavones, lipid oxidation, obesity, phytoestrogens. Environ Health Perspect 115:1467–1473 (2007) . doi:10.1289/ehp.10413 available via http://dx.doi.org/ [Online 12 July 2007]
Address correspondence to S. Nef, Department of Genetic Medicine and Development, Faculty of Medicine, University of Geneva, rue Michel Servet 1, CH-1211 Geneva 4, Switzerland. Telephone: 41 22 379 5193. Fax: 41 22 379 5260. E-mail: Serge.Nef@medecine.unige.ch Supplemental Material is available online at http://www.ehponline.org/members/2007/10413/suppl.pdf We thank L. Tropia, C. Vesin, G. Sealy, A. Fort, L. Lehr, C. Barraclough, and D. Cholet for technical assistance ; S. Ferrari and D. Pierroz for access to the DEXA analysis ; U. Schibler and P. Gos for the running-wheel activity test ; and P. Bonfils and I. Bolon for advice on animal care. This work was funded by grants from the Swiss National Science Foundation (NRP50, 4050-104375 to S.N.) and The Sir JulesThorn Charitable Overseas Trust Reg., Schaan. The authors declare they have no competing financial interests. Received 27 April 2007 ; accepted 12 July 2007.
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