A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice

Environ Health Perspect. 2007 Oct;115(10):1467-73. doi: 10.1289/ehp.10413.


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 alpha and beta 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.

Keywords: AgRP; endocrine disruptors; isoflavones; lipid oxidation; obesity; phytoestrogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / drug effects*
  • Agouti-Related Protein / drug effects
  • Animal Feed
  • Animals
  • Case-Control Studies
  • Cold Temperature
  • Energy Metabolism / drug effects*
  • Isoflavones / blood*
  • Isoflavones / pharmacology
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Obesity
  • Phytoestrogens / metabolism
  • Phytoestrogens / pharmacology*
  • Soybeans / chemistry*


  • Agouti-Related Protein
  • Agrp protein, mouse
  • Isoflavones
  • Phytoestrogens