Endocrine Abstracts

Androgen is an important factor for determining body composition in males. Abdominal obesity is inversely correlated with serum androgen levels in men. Androgen receptor (AR) null male mice revealed late-onset visceral obesity, accompanying energy balance abnormality. We previously reported a novel synthetic steroid, S42 as a promising candidate of a selective androgen receptor modulator (SARM). When orchiectomized Sprague-Dawley rats were administered with S42 for 3 weeks, the muscle weight of the levator ani was increased as markedly as that induced by dihydrotestosterone (DHT), but the weight of the prostate was not elevated at any doses in contrast to DHT. In addition, although the plasma triglyceride level was unaffected by DHT, it was significantly reduced by S42. Taken together, S42 works as an AR agonist in muscle and as an AR antagonist in the prostate, accompanying beneficial potentials on lipid metabolism. We then administered S42 (10 mg/kgBW) by intraperitoneal injection in high-fat diet induced obese mouse model for 16 weeks and found that S42 significantly decreased the body weight (BW) compared with the placebo administration without affecting the food intake. The BW reduction was accompanied by the marked reduction of visceral fat determined by the CT analysis. The aggravated insulin sensitivity by high fat diet was also improved by the S42 treatment but not by placebo. A similar effect of S42 was also observed when S42 was administered to ob/ob mouse for 4 weeks. S42 could reduce the BW with marked reduction of visceral fat in ob/ob mouse. These results suggest that S42 have some beneficial metabolic effect on fat accumulation and insulin sensitivity in vivo.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.