Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner.

The soy isoflavone genistein targets adipose tissue and elicits
physiological effects that may vary based on dietary intake.
We hypothesized that the adipose effects of genistein are dose
and gender dependent. Four-week-old C57BL/6 male and female
mice received daily oral doses of genistein (50–200,000
g/kgd) or 17-estradiol (E2) (5 g/kgd) for 15 d or a diet
containing 800 ppm genistein. Genistein increased epididymal
and renal fat pad and adipocyte size at doses up to 50,000
g/kgd or at 800 ppm in the diet in males but not in females.
The alteration in adipocity correlated with changes in peripheral
insulin resistance. These treatments increased
genistein serum concentrations from 356 to 10326 nM 12 h
after treatment and lowered plasma triglycerides and cholesterol
levels. The 200,000 g/kgd genistein dose decreased adipose
tissue weight similarly to E2. This genistein dose downregulated
estrogen receptor ( more than) and progesterone
receptor expression and induced estrogen-dependent adipose
differentiation factors; it did not change expression of the
minimal consensus estrogen-responsive element in ERE-tKLUC
mice, which was positively modulated in other tissues
(e.g. the lung). E2 down-regulated almost all examined adipogenic
factors. Gene microarray analysis identified factors in
fat metabolism and obesity-related phenotypes differentially
regulated by low and high doses of genistein, uncovering its
adipogenic and antiadipogenic actions. The lower dose induced
the phospholipase A2 group 7 and the phospholipid
transfer protein genes; the 200,000 g/kgd dose inhibited
them. The antiadipogenic action of genistein and down-regulation
of adipogenic genes required the expression ofER. In
conclusion, nutritional doses of genistein are adipogenic in a
gender-specific manner, whereas pharmacological doses inhibited
adipose deposition.