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


OBJECTIVE
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.


CONCLUSIONS
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.
Cederroth
Christopher R
CR
Department of Genetic Medicine and Development and National Center for Competence in Research - Frontiers in Genetics, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Vinciguerra
Manlio
M
Kühne
Françoise
F
Madani
Rime
R
Doerge
Daniel R
DR
Visser
Theo J
TJ
Foti
Michelangelo
M
Rohner-Jeanrenaud
Françoise
F
Vassalli
Jean-Dominique
JD
Nef
Serge
S
D050154:Adiposity / Q000187:drug effects*; D054369:Agouti-Related Protein / Q000187:drug effects; D000821:Animal Feed; D000818:Animals; D016022:Case-Control Studies; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects*; D007529:Isoflavones / Q000097:blood* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D009765:Obesity; D048789:Phytoestrogens / Q000378:metabolism / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*
D054369:Agouti-Related Protein; C515199:Agrp protein, mouse; D007529:Isoflavones; D048789:Phytoestrogens