Importance of estrogen receptors in adipose tissue function

Abstract

Adipose tissue dysfunction belongs to the primary defects in obesity and may link excessive fat accumulation to several health problems including increased risk of insulin resistance, type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, atherosclerosis, dementia, and certain forms of cancer [1]. Symptoms of adipose tissue (AT) dysfunction include ectopic fat deposition in visceral depots, adipocyte hypertrophy, increased number of immune cells infiltrating AT, impaired insulin sensitivity and lipolysis in adipocytes, and the production of a proinflammatory, atherogenic, and diabetogenic adipokine pattern [1]. In this context, it is important to note that approximately 10–15% of obese individuals are protected against obesity-associated metabolic and cardiovascular diseases and therefore called metabolically healthy or insulin sensitive obese [2]. Metabolically healthy obesity may result from preserved adipose tissue function and is more frequently observed in pre-menopausal women compared to both postmenopausal women and men [1]. Moreover, there are significant differences in fat distribution, adipocyte and AT function between men and women, which may, to a large extent, result from gender differences in estrogen receptor expression [3]. In postmenopausal women, decreased circulating estrogens may contribute to the development of visceral obesity and subsequent metabolic disorders—a phenomenon, which can be partly reversed by estrogen replacement therapy [4]. Visceral and subcutaneous abdominal fat distribution (often referred to as male type of fat distribution) is commonly associated with metabolic complications of obesity, whereas lower-body fat (gluteal-femoral), which is considered the typical “female fat distribution”, may be protective. Investigating metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate AT function distinctly in men and women, is a goal of current research endeavors. During the past decades, it has become clear that there are gender-dependent differences in AT biology, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, as well as AT's secretory function. The well recognized effects of estrogens in the regulation of glucose homeostasis and lipid metabolism may at least in part be due to their action in adipose tissue. In this issue of Molecular Metabolism, Davis and co-workers provide novel experimental evidence that AT and adipocyte estrogen receptor alpha (ERα) play an important role in maintaining AT function and protecting AT against inflammatory damage [5]. The first notion that estrogen/ERα signaling may be associated with obesity and the development of AT comes from studies of ERα whole body knockout