Prepubertal androgen signaling is required to establish male fat distribution

Fat distribution is sexually dimorphic and is associated with metabolic disease risk. It is unknown if prepubertal sex-hormone signaling influences adult fat distribution. Here, we show that karyotypically male androgen-insensitive mice exhibit pronounced subcutaneous adiposity compared with wild-type males and females. This subcutaneous adipose bias emerges prior to puberty and is not due to differences in adipocyte size or rates of adipogenesis between visceral and subcutaneous fat. Instead, we find that androgen-insensitive mice lack an adequate progenitor pool for normal visceral-fat expansion during development, thus increasing the subcutaneous-to-visceral-fat ratio. Obesogenic visceral-fat expansion is likewise inhibited in these mice, yet their metabolic health is similar to wild-type animals with comparable total fat mass. Taken together, these data show that adult fat distribution can be determined prior to the onset of puberty by the relative number of progenitors that seed nascent adipose depots.