The role of estrogen and estrogen receptor-α in male adipose tissue

Abstract

Males and females both express estrogen receptor (ER) in white adipose tissue (WAT), and estrogens appear to play an important role in regulating WAT in females. However, the role of ER in male WAT was unclear. In this review, we describe our work, which used wild type (WT) and ERα-knockout (αERKO) male and female mice to determine the role of ERα in regulating WAT and brown adipose tissue (BAT). There were progressive increases in WAT with advancing age in αERKO compared with WT males; weights of various WAT depots in αERKO males were increased by more than 100% compared with WT controls during adulthood. Conversely, BAT weight was similar in αERKO and WT males at all ages. Adipocyte areas and numbers were also increased in WAT from αERKO compared with WT males. Compared with WT controls, αERKO females also had increases in WAT. The αERKO mice also had insulin resistance and impaired glucose tolerance, similar to humans lacking ERα or aromatase. The obesity in αERKO males appeared to involve decreased energy expenditure rather than hyperphagia. In summary, ERα absence causes adipocyte hyperplasia and hypertrophy in WAT, but not BAT, and is accompanied by insulin resistance and glucose intolerance in both males and females. These results are the first evidence that the estrogen/ERα signaling system is critical in female and male WAT deposition, and may have clinical implications.