Sexual Dimorphism's impact on adipogenesis: A three-dimensional in vitro model treated with 17β-estradiol and testosterone.

Using a three-dimensional (3-D) in vitro culture model, we report the dose dependent effect of 17β-estradiol and testosterone on the adipogenic differentiation and maturation of human adipose derived stem cells (hASCs) obtained from female and male patients. Considering sexual dimorphism, we expected male and female adipocytes to respond differently to the sex steroids. Both male and female hASC spheroids were exposed to 100 nM and 500 nM of 17β-estradiol and testosterone either at the beginning of the adipogenic maturation (Phase I) to discourage intracellular triglyceride accumulation or exposed after adipogenic maturation (Phase II) to reduce the intracellular triglyceride accumulation. The results show that 17β-estradiol leads to a dose dependent reduction in intracellular triglyceride accumulation in female hASC spheroids compared to the both untreated and testosterone-treated cells. Affirming our hypothesis, 17β-estradiol prevented intracellular triglyceride accumulation during Phase I, while it stimulated lipolysis during Phase II. PPAR-γ and adiponectin gene expression also reduced upon 17β-estradiol treatment in female cells. Interestingly, 17β-estradiol and testosterone had only a modest effect on the male hASC spheroids. Collectively, our findings suggest that 17β-estradiol can prevent fat accumulation in adipocytes during early and late stages of maturation in females.