Metabolic Adaptations and Substrate Oxidation are Unaffected by Exogenous Testosterone Administration during Energy Deficit in Men

Med Sci Sports Exerc. 2023 Apr 1;55(4):661-669. doi: 10.1249/MSS.0000000000003089. Epub 2022 Nov 22.

Abstract

Introduction/purpose: The effects of testosterone on energy and substrate metabolism during energy deficit are unknown. The objective of this study was to determine the effects of weekly testosterone enanthate (TEST; 200 mg·wk -1 ) injections on energy expenditure, energy substrate oxidation, and related gene expression during 28 d of energy deficit compared with placebo (PLA).

Methods: After a 14-d energy balance phase, healthy men were randomly assigned to TEST ( n = 24) or PLA ( n = 26) for a 28-d controlled diet- and exercise-induced energy deficit (55% below total energy needs by reducing energy intake and increasing physical activity). Whole-room indirect calorimetry and 24-h urine collections were used to measure energy expenditure and energy substrate oxidation during balance and deficit. Transcriptional regulation of energy and substrate metabolism was assessed using quantitative reverse transcription-polymerase chain reaction from rested/fasted muscle biopsy samples collected during balance and deficit.

Results: Per protocol design, 24-h energy expenditure increased ( P < 0.05) and energy intake decreased ( P < 0.05) in TEST and PLA during deficit compared with balance. Carbohydrate oxidation decreased ( P < 0.05), whereas protein and fat oxidation increased ( P < 0.05) in TEST and PLA during deficit compared with balance. Change (∆; deficit minus balance) in 24-h energy expenditure was associated with ∆activity factor ( r = 0.595), but not ∆fat-free mass ( r = 0.147). Energy sensing (PRKAB1 and TP53), mitochondria (TFAM and COXIV), fatty acid metabolism (CD36/FAT, FABP, CPT1b, and ACOX1) and storage (FASN), and amino acid metabolism (BCAT2 and BCKHDA) genes were increased ( P < 0.05) during deficit compared with balance, independent of treatment.

Conclusions: These data demonstrate that increased physical activity and not exogenous testosterone administration is the primary determinate of whole-body and skeletal muscle metabolic adaptations during diet- and exercise-induced energy deficit.

Trial registration: ClinicalTrials.gov NCT02734238.

Publication types

  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Energy Metabolism* / physiology
  • Exercise / physiology
  • Humans
  • Male
  • Oxidation-Reduction
  • Polyesters
  • Testosterone*

Substances

  • Testosterone
  • Polyesters

Associated data

  • ClinicalTrials.gov/NCT02734238