Androgen (dihydrotestosterone)-mediated regulation of food intake and obesity in female mice

Abstract

To better understand how elevated androgen levels regulate food intake and obesity in females, we treated ovariectomized female mice with dihydrotestosterone (DHT) (non-aromatazable androgen), measured food intake and body weight, and evaluated physiological changes in liver function, glucose tolerance, and leptin resistance. Ovariectomized mice were treated with DHT or placebo. Mice were then fed a high fat diet under free-feeding or pair-feeding conditions for 3 months. We found that when DHT-treated ovariectomized mice had free access to food (free-feeding), they had increased food intake and higher body weight compared with control animals. These mice also had a significantly greater accumulation of fat in the liver and exhibited increased fasting glucose, impaired glucose tolerance, and resistance to leptin. However, when these mice were placed on a restricted diet and fed the same caloric amounts as controls (pair-feeding), their body weight increased at the same rate as control animals. This suggests that androgen regulates food intake through altered leptin sensitivity, and this increase of food intake could significantly contribute to an obesity phenotype. In summary, we demonstrated a role for androgen in the regulation of food intake and weight gain in females using a mouse model. This model will be useful to further elucidate the role of elevated androgen in females.

Keywords: ACC1; ACC2; ALT; ARC; Androgen; DHT; Dihydrotestosterone; Fas; Females; Food intake; G6Pase; IACUC; Institutional Animal Care and Use Committee; MCH; OVX; Obesity; Ovariectomized mice; PCOS; PCR; PEPCK; POMC; SCD; SREBP1c; WAT; acetyl-CoA carboxylase 1; acetyl-CoA carboxylase 2; arcuate nucleus; dihydrotestosterone; fatty acid synthetase; glucose 6-phosphatase; melanin concentration hormone-1; ovariectomized; phosphoenolpyruvate carboxykinase; polycystic ovary syndrome; polymerase chain reaction; pro-opiomelanocortin; serum alanine aminotransferase; stearoyl-CoA desaturase; sterol regulatory element-binding protein 1c; white adipose tissue.