Androgens and body fat distribution

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Abstract

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.

Section snippets

Body fat distribution and metabolic alterations

The importance of obesity and body fat distribution in the development of type 2 diabetes and cardiovascular disease is of growing interest in the context of the worldwide obesity epidemic [1], [2], [3]. Adipose tissue accumulation within the abdominal cavity (visceral obesity) has been identified as a critical correlate of obesity-related metabolic disorders leading to insulin resistance, hyperinsulinemia, a dyslipidemic state and proinflammatory/prothrombotic alterations [4], [5], [6].

Sex-specificity of body fat distribution

There is a striking sex difference in body fat distribution between men and women. Men tend to accumulate adipose tissue in the abdomen (android fat distribution) while women tend to accumulate fat in the gluteal-femoral region (gynoid fat distribution). Abdominal adipose tissue areas measured by imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) also show a clear sex-related difference. In men, abdominal adipose tissue tends to accumulate in the visceral

Studies in men

Abdominal obesity is usually associated with low plasma testosterone levels in cross-sectional [14] as well as in longitudinal [15], [16] studies. Waist circumference and waist-to-hip ratio are also inversely associated with plasma sex hormone-binding globulin (SHBG) levels in these studies [14], [15], [16]. These results are confirmed by many studies which have measured abdominal fat areas using CT or MRI. In such studies, visceral fat accumulation measured by CT is significantly correlated

Exogenous androgens and body fat distribution

Elbers et al. [37], [38], [39] have shown that testosterone administration (250 mg intramuscular testosterone ester injections every 2–3 weeks) in female-to-male transsexuals changes their body fat distribution toward a more android pattern. In the latter studies, abdominal adipose tissue was assessed using MRI.

On the other hand, androgen treatment in hypogonadal men leads to a decrease in waist-to-hip ratio in one study [40]. No change in waist-to-hip ratio was observed after testosterone or

Androgens and adipose tissue function

Some studies have examined adipocyte cell size, lipoprotein lipase and lipolytic activities after androgen treatment in humans. Adipocyte size was decreased in abdominal subcutaneous and gluteal depots in female-to-male transsexuals under testosterone treatment [48]. Basal lipolysis in these subjects was significantly increased in abdominal but not in gluteal adipose tissue [48]. Rebuffé-Scrive et al. [49] have shown that norepinephrine-stimulated lipolysis was increased and LPL activity

Local androgen metabolism in adipose tissue and body fat distribution

The adrenal gland secretes steroid precursors of active sex hormones. From these precursors, the regulation of local sex steroid hormone concentrations can be achieved separately in each peripheral tissue. This process, termed “intracrinology”, depends on the tissue expression of specific enzymes involved in the synthesis and inactivation of sex steroid hormones [90]. Adipose tissue is known to express several steroidogenic and steroid-inactivating enzymes (reviewed in ref. [91]).

Several lines

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  • Cited by (0)

    Presented at the ‘12th International Congress on Hormonal Steroids and Hormones & Cancer’ (Athens, Greece, 13–16 September 2006).

    1

    Karine Blouin is the recipient of a Canadian Institutes of Health Research studentship.

    2

    André Tchernof is the recipient of a Canadian Institutes of Health Research Scholarship.

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