Androgens Decrease Plasma Adiponectin, an Insulin-Sensitizing Adipocyte-Derived Protein

Abstract

Adiponectin, an adipose-specific secretory protein, exhibits antidiabetic and antiatherogenic properties. In the present study, we examined the effects of sex hormones on the regulation of adiponectin production. Plasma adiponectin concentrations were significantly lower in 442 men (age, 52.6 ؎ 11.9 years [mean ؎ SD]) than in 137 women (53.2 ؎ 12.0 years) but not different between pre-and postmenopausal women. In mice, ovariectomy did not alter plasma adiponectin levels. In contrast, high levels of plasma adiponectin were found in castrated mice. Testosterone treatment reduced plasma adiponectin concentration in both sham-operated and castrated mice. In 3T3-L1 adipocytes, testosterone reduced adiponectin secretion into the culture media, using pulse-chase study. Castration-induced increase in plasma adiponectin was associated with a significant improvement of insulin sensitivity. Our results indicate that androgens decrease plasma adiponectin and that androgen-induced hypoadiponectinemia may be related to the high risks of insulin resistance and atherosclerosis in men.

Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex

“…In addition, in a multiple linear regression analysis that included body size and body fat distribution, sex again had an independent effect on adiponectin concentrations. This finding of a sex-based difference in plasma adiponectin concentra- tions is supported by some [28,31,55] but not all [30,56] other studies. However, the current findings are the first to account for the known sex-based differences in body fat distributions and strongly support the concept that sex has an additional independent effect to modulate adiponectin concentrations.…”

“…The number of fat cells and fat cell size, both of which vary between sexes, are possible determinants of adiponectin production rates. Furthermore, it was recently reported that androgens decrease plasma adiponectin concentrations in vivo as well as adiponectin secretion from 3T3-L1 adipocytes in vitro [55].…”

“…These changes would be predicted to be associated with a decline in adiponectin concentrations with age, yet we observed the opposite. Sex steroids could be responsible for some of these changes as both testosterone [55] and estrogen have been shown to inhibit adiponectin production [61] and they both decline with age. A reduction in adiponectin clearance in older individuals is another possible contributor to the agerelated increase in adiponectin.…”

The prospective association between adiponectin and coronary artery disease among individuals with type 1 diabetes. The Pittsburgh Epidemiology of Diabetes Complications Study

“…Androgens reduce plasma adiponectin, explaining the lower plasma protein levels observed among men, as well as some of the increased risk of insulin resistance and atherosclerosis in these individuals, compared with women [47]. Surprisingly, adiponectin levels were elevated among individuals with macroalbuminuria compared with those with normal albumin excretion.…”

Adiponectin complexes in human cerebrospinal fluid: distinct complex distribution from serum

“…Sexual dimorphism in terms of total systemic adiponectin, with women having higher levels of adiponectin than men, has been reported [10,42,43]. Although this was preserved in CSF [18], such findings were achieved using assay-based measures.…”