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

Document Type

Article

Publication Date

4-1-2023

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 (Δ; deficit minus balance) in 24-h energy expenditure was associated with Δactivity factor (r = 0.595), but not Δfat-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.

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