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

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 ER alpha -knockout (alpha ERKO) male and female mice to determine the rule of ER alpha in regulating WAT and blown adipose tissue (BAT). There were progressive increases in WAT with advancing age in alpha ERKO compared with WT males; weights of various WAT depots in alpha ERKO males were increased by more than 100% compared with WT controls during adulthood. Conversely, BAT weight was similar in alpha ERKO and WT males at all ages. Adipocyte areas and numbers were also increased in WAT from alpha ERKO compared with WT males. Compared with WT controls, alpha ERKO females also had increases in WAT. The alpha ERKO mice also had insulin resistance and impaired glucose tolerance, similar to humans lacking ER alpha or aromatase. The obesity in alpha ERKO males appeared to involve decreased energy expenditure rather than hyperphagia. In summary, ER alpha 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/ER alpha signaling system is critical in female and male WAT deposition, and may have clinical implications. (C) 2001 Elsevier Science ireland Ltd. All rights reserved.