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

Abstract

Background 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). Methods 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. Results 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. Conclusions Testosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling.

Endogenous Androgens Diminish Food Intake and Activation of Orexin A Neurons in Response to Reduced Glucose Availability in Male Rats

“…This result is consistent with the results of Chai’s study, in which they reported that orchiectomy reduced daily food intake up to five days after the surgery but did not affect daily food intake thereafter [ 20 ]. The data in the present study and earlier studies suggest that androgens affect body weight and body composition by modifying metabolism more prominently than feeding behavior [ 1 , 12 , 13 ].…”

“…Animal studies have demonstrated that gonadectomy in male animals (orchiectomy) reduces and testosterone augments body weight gain, and androgen increases lean body mass and decreases fat mass [ 12 ]. On the other hand, the role of androgens in the regulation of food intake is controversial; some studies reported that androgen increased body weight gain with increased food intake, while other studies reported androgen increased body weight gain without altering daily food intake [ 1 , 13 ].…”

Rapeseed (canola) oil aggravates metabolic syndrome-like conditions in male but not in female stroke-prone spontaneously hypertensive rats (SHRSP)

“…On the other hand, significantly suppressed testosterone production was observed in male SHRSP given a CAN diet for 13 weeks, compared to animals given a SOY diet [ 12 ]. These findings imply that CAN ingestion promotes metabolic syndrome-like conditions by lowering the testosterone level in male SHRSP, since it is well known that testosterone deficiency is associated with metabolic syndrome in men and induces metabolic syndrome-like symptoms in rodents, as well [ [13] , [14] , [15] ]. In fact, the prevalence in men of metabolic syndrome is affected by androgen, and a decreased level of testosterone is connected with increased mortality in elderly men [ 16 ].…”

Mitochondria in Sex Hormone-Induced Disorder of Energy Metabolism in Males and Females

“…Testosterone controls energy metabolism through the actions in several organs, including the brain (55), skeletal muscle, adipose tissue (56), liver, and pancreatic islet cells (4,13,57,58). Here, the discussion focuses on the liver for the availability of transcriptomic data.…”

“…In testosterone-deficient patients and animals, decreased catabolism of energy substrates increased the risk of obesity. For example, castration of male rats induced expression of fatty acid synthesis-related genes, thereby leading to fat accumulation in the skeletal muscle and increased subcutaneous fat deposition in normal diet-fed rats (58). In the skeletal muscle, androgens promote myogenesis in male mice and humans by enhancing the expression of glycogen synthase, GLUT4, and insulin receptor substrate 1 (IRS1) (19).…”