**1. Introduction**

Obesity is a process by which excess energy accumulates and results in increasing fat deposition in various parts of the body. Obesity is associated with economic, social, and lifestyle factors, and is commonly induced by imbalanced energy intake and consumption of high calorie foods or low physical activity. Obesity is a worldwide issue in public health that significantly increases the risk for type 2 diabetes, metabolic syndrome, atherosclerosis, and cardiovascular disease.

Body weight increases with aging in both genders, irrespective of the baseline weight in normal and obese individuals [1]. This increase in body weight is attributed to a reduction in energy expenditure with decreased physical activity. The global prevalence of obesity has been reported to be higher in females than males [2]. A US population survey estimated that approximately two thirds of women 40 - 60 years of age are overweight or obese [3].

In addition to aging, the menopause is considered an important factor for contributing to altered adiposity in women. Menopause is defined as a decline in endogenous estrogen production from the ovaries, and clinically represents cessation of menstruation and loss of fertility. Estrogen loss is the most significant event impacting a variety of physiologic and psychological changes in women. In the peri- or postmenopausal period, a change in adiposity has been well described. Weight gain during the menopausal transition has been scrutinized as a critical factor to midlife body weight in women [1]. Several observational studies have shown increased weight gain during the menopausal transition [4, 5]. A number of clinical trials have demonstrated a significant association between menopausal status with changes in anthropometry, blood pressure, lipid profile, and glucose/insulin metabolism [6-11], which can be linked to increased cardiovascular morbidity and mortality during the postmenopausal period [12].

Given the collective evidence on the change in adiposity across the menopausal transition, the roles of sex hormones, especially estrogen, are of increased interest in understanding the regulation of adiposity. This review discusses the association between estrogen and adiposity, and the interaction of estrogen with other biological metabolites and substances

Adipose Tissue Metabolism and Effect of

[24, 25].

therapy [27, 28].

adiposity.

Postmenopausal Hormone Therapy on Change of Body Composition 293

during 4 years of follow-up showed an increase in visceral adipose tissue and total body fat, and a 32% reduction in fat oxidation during the menopausal transition [4]. In the study, the subcutaneous adipose tissue increased in accordance with age independent of menopausal status, while the findings of increased visceral adipose tissue and total body fat were noted only in postmenopausal women. This distinctive physiologic change in amount and distribution of fat in women is noteworthy because the central fat deposition has a more deleterious effect on the development of cardiovascular and metabolic disease

Although the exact mechanism regarding fat redistribution after menopause remains unclear, the phenomenon with declining estrogen level may be due to alterations in adipose tissue metabolism [4]. Several studies have shown that estrogen directly promotes subcutaneous fat accumulation [26], and the loss of estrogen by menopause is associated with an increase in central fat. Several longitudinal studies lend support in suggesting that estrogen plays an important role in regulating body fat distribution. Postmenopausal women who receive estrogen replacement have significantly lower waist-to-hip ratios and less visceral adipose tissue than women who have never received estrogen replacement

In experimental studies, 17β-estradiol (E2) has been shown to regulate adipose tissue by increasing the number of adipocytes through effects on proliferation and differentiation [29, 30]. The number and size of adipocytes is a determining factor for adiposity, and the adipocyte size is balanced by lipogenesis and the lipolysis pathway. Palin et al. have found a direct regulatory effect of E2 on the expression of lipoprotein lipase (LPL) and hormonesensitive lipase (HSL) in human subcutaneous abdominal adipose tissue [31]. LPL is a major modulator of lipid deposition as triglycerides into adipocytes, and HSL is the rating-limiting enzyme involved in the process of lipolysis. Therefore, the direct effect of estrogen on these

As other mechanisms suggest, the role of the estrogen receptor (ER) is focused on estrogenrelated action on the regulation of adiposity. Adipocytes express two main subtypes of ERs (alpha [ERα] and beta [ERβ]). ERα was discovered first, and the biological effects of ERα on adiposity have been thoroughly described. ERα is considered to be essential for genomic actions of E2 on the regulation of body fat [32]. Because the hypothalamic nuclei that regulate energy homeostasis express ERα, E2 action could affect adiposity [33-35]. An animal study conducted by Heine et al. demonstrated that glucose intolerance, hypertrophy, and hyperplasia of adipocytes are induced in ERα knockout mice [36], thus supporting a

In contrast, the biological implications of the more recently discovered ERβ have been less revealing than ERα. The binding affinity of estrogen to ERα and ERβ is known to be similar, but the two subtypes of ER only have 56% identity in the ligand binding domain [26, 37, 38]. Therefore, different or competitive roles between both ERs have been repeatedly suggested. Naaz et al. studied the role of ERβ in adipose tissue [39] in mice with ERαKO. When compared to the results generated in ERαKO mice, it was shown that removing E2/ERβ signaling induced a decrease in body weight, the amount of fat, and adipocyte size. Therefore, the authors suggested a potential role for ERβ in regulating adiposity, as well as ERα, but with opposing actions. Thus, the roles for ERs in adipocytes might be an interesting target to further elucidate the estrogen effects on regulating

enzymes might lead to fat redistribution in postmenopausal women.

critical role of ERα in determining adiposity.

involved in obesity. In addition we summarize evidence for the effect of postmenopausal hormone therapy (HT) on changes in body composition.
