Interrelationships of serum androgens, omental adipose tissue metabolism, and nonalcoholic fatty liver disease in obese premenopausal women.

Background: The concept that androgens regulate multiple aspects of adipose tissue metabolism in women is based on studies of women with pathological androgen excess and in vitro studies generally using supraphysiological androgen concentrations. We investigated whether in women with normal-range serum testosterone, relationships exist between serum androgens and expression of proinflammatory (tumor necrosis factor-α, interleukin-6, CD68), anti-inflammatory (adiponectin), and lipid metabolic (lipoprotein lipase, hormone sensitive lipase) genes in omental adipose tissue, and severity of nonalcoholic fatty liver disease (NAFLD).

Methods: We studied obese women undergoing laparoscopic gastric band surgery (premenopausal, regular menses, nondiabetic, serum testosterone <2.5 nmol/L, n=27). Gene expression was measured in omental adipose tissue. Liver biopsies were examined in 22 participants.

Results: Serum testosterone or androstanediol glucuronide (an indicator of peripheral androgen metabolism) were not related to markers of inflammation or lipid metabolism in omental adipose tissue. In women with NAFLD, there was a significant trend to higher serum free testosterone, serum insulin, and insulin resistance with increasing severity of liver pathology; however, markers of inflammation in omental adipose tissue did not differ. Omental lipoprotein lipase expression was significantly increased in women with nonalcoholic steatohepatitis (NASH).

Conclusions: These primarily correlative data suggest that physiological-range androgen levels do not influence inflammation or lipid metabolism in omental adipose tissue of women, but further studies of direct androgen effects on adipose tissue are needed for confirmation. Androgens may still play a role in the pathogenesis of NAFLD in women, via mechanisms unrelated to omental adipose tissue metabolism.