Testosterone deficiency caused by castration increases adiposity in male rats in a tissue-specific and diet-dependent manner

Myunggi Baik, Jin Young Jeong, Seung Ju Park, Seon Pil Yoo, Jin Oh. Lee, Jae Sung Lee, Md Najmul Haque, Hyun-Jeong Lee

Testosterone deficiency in men is clinically associated with the development of metabolic syndrome, which manifests as obesity, hepatic steatosis, and type-2 diabetes. We investigated the effects of castration-induced testosterone deficiency on body adiposity and the expression of genes related to lipid metabolism and glucose uptake and androgen signaling in male rats fed a normal diet (ND) or a high-fat diet (HFD). Changes in lipid and glucose metabolism and androgen signaling were investigated at physiological and molecular levels in the muscle, liver, and adipose tissues of non-castrated and castrated rats under ND or HFD feeding. Castration-induced testosterone deficiency predisposed animals on ND to early development of fatty liver by activating fatty acid (FA) synthesis, whereas HFD activated hepatic FA uptake CD36 expression, leading to the development of hepatic steatosis. In rats fed ND, castration induced muscle fat accumulation by activating CD36 expression. In the subcutaneous fat of ND-fed rats, castration increased adiposity and the expression of FA synthesis-related genes, but it decreased glucose transporter gene expression. In the abdominal fat of rats fed ND, castration increased adiposity by upregulating FA synthesis-related genes, and HFD promoted adiposity by inducing FA uptake, glucose transporter, and FA synthesis-related gene expression. In rats fed ND, castration decreased body growth and muscle weight and downregulated the expression of genes androgen signaling in the longissimus dorsi muscle. Testosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling.