Late-onset
hypogonadism (i.e.
androgen deficiency) raises the risk for
abdominal obesity in men. The mechanism for this
obesity is unclear. Here, we demonstrated that
hypogonadism after
castration caused
abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with
antibiotics that disrupt the intestinal microflora. In HFD-fed mice,
castration increased feed efficiency and decreased fecal weight per food intake.
Castration also induced in an increase of visceral fat mass only in the absence of
antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by
castration irrespective of
antibiotics.
Castration reduced the expression in the mesenteric fat of both adipose
triglyceride lipase and
hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of
antibiotics.
Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting
blood glucose levels, and increased liver
triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with
antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that
androgen (e.g.
testosterone) deficiency can alter the intestinal microbiome and induce
abdominal obesity in a diet-dependent manner.