Metabolic Effects of Testosterone Hormone Therapy in Normal and Orchiectomized Male Rats: From Indirect Calorimetry to Lipolytic Enzymes

Changes in total energy expenditure (TEE) and substrate metabolism may help explain the metabolic actions of testosterone (T). This study measured respiratory quotient (RQ), TEE, ghrelin, insulin, and key lipolysis enzyme concentrations in relation to body weight (wt) and food intake (FI) in both normal and bilaterally orchiectomized rats with/without T treatment.

T administration in orchiectomized rats significantly increased orexigenic mediators such as ghrelin and insulin without inducing any significant changes in wt. The mechanism for this finding might be the increased TEE and the stimulation of lipolysis through the ATGL enzyme. The associated rise of GH might help in interference with accumulation of lipid in adipose tissue. Apart from the effect on GH, T-Sham showed similar effects of T supplementation.

In total, thirty-two male Wistar rats (300-400 g) were divided into four groups (n = 8/group), including (a) sham-operated and vehicle-injected group (Sham), (b) T-treated sham group (T-Sham) for which sham-operated rats were injected with IM testosterone undecanoate (100 mg/kg, for one week), (c) orchiectomy and vehicle-injected group (Orch), and (d) T-replaced orchiectomy group (T-Orch). After one week, FI and wt were automatically recorded, indirect calorimetry parameters were measured, and blood samples were collected to measure T, ghrelin, insulin, growth hormone (GH), glucose, hormone-sensitive lipase (HSL), adipocyte triglyceride lipase (ATGL), free fatty acids (FFA), and lipid profiles.

Orchiectomy decreased ghrelin, GH, and insulin levels, increased TEE and RQ, and lowered FI and wt. The T-Orch group exhibited increased levels of ghrelin (3-fold), insulin, GH, blood levels of lipolysis products, TEE, and FI in addition to reduced glucose levels (P < 0.05). This group demonstrated no significant changes in wt. In the T-Sham group, T increased ghrelin and insulin levels (P < 0.05) with strong positive correlations (r = 0.663 and 0.644, respectively, P < 0.05), increased ATGL levels, RQ toward carbohydrate utilization ranges, and TEE, and reduced HSL levels (P < 0.05) with insignificant changes in FI or wt. Conclusions: T administration in orchiectomized rats significantly increased orexigenic mediators such as ghrelin and insulin without inducing any significant changes in wt. The mechanism for this finding might be the increased TEE and the stimulation of lipolysis through the ATGL enzyme. The associated rise of GH might help in interference with accumulation of lipid in adipose tissue. Apart from the effect on GH, T-Sham showed similar effects of T supplementation.