Ablation of steroid receptor coactivator-3 in mice impairs adipogenesis and enhances energy expenditure

Abstract

Obesity is a medical condition in which excess body fat has accumulated to an extent and may have an adverse effect on health, leading to reduced life expectancy, impaired energy homeostasis and increased health problems. The p160 steroid receptor coactivator (SRC) gene family members have been suggested to be involved in energy homeostasis, but the impact of SRC-3 ablation on white and brown adipose tissue needs to be elucidated. In the current study, we collected in vivo data and carried out morphological studies on the effect of SRC-3 deficiency on white adipose tissue (WAT) and brown adipose tissue (BAT). Primary cells were cultured to investigate the differentiation ability of both adipocytes. Western blot was applied to detect the expression of master genes governing adipogenesis and thermogenesis. We observed that SRC-3^{−/−} mice were lean, with reduced WAT and decreased serum leptin levels, mainly due to the smaller white adipocyte size caused by impaired adipogenesis, presented by decreased peroxisome proliferator activated receptor g (PPARg) expression. In the BAT, the lipid droplets decreased significantly in SRC-3^{−/−} mice as demonstrated by histological analysis and electron microscopic observation, which could be explained by enhanced thermogenesis. The expression of thermogenic marker gene PPARg coactivator 1α and uncoupling protein-1 increased in BAT of SRC-3^{−/−} mice, which proved our observations. Collectively, these results demonstrate that SRC-3 plays a key role in adipogenesis and energy expenditure.

Keywords

steroid receptor coactivator-3 / white adipose tissue / brown adipose tissue / obesity / adipocytes / energy expenditure