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Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit.

ABSTRACT: Testosterone supplementation during energy deficit promotes whole body lean mass accretion, but the mechanisms underlying that effect remain unclear. To elucidate those mechanisms, skeletal muscle molecular adaptations were assessed from muscle biopsies collected before, 1 h, and 6 h after exercise and a mixed meal (40 g protein, 1 h postexercise) following 14 days of weight maintenance (WM) and 28 days of an exercise- and diet-induced 55% energy deficit (ED) in 50 physically active nonobese men treated with 200 mg testosterone enanthate/wk (TEST) or placebo (PLA) during the ED. Participants (n = 10/group) exhibiting substantial increases in leg lean mass and total testosterone (TEST) were compared with those exhibiting decreases in both of these measures (PLA). Resting androgen receptor (AR) protein content was higher and fibroblast growth factor-inducible 14 (Fn14), IL-6 receptor (IL-6R), and muscle ring-finger protein-1 gene expression was lower in TEST vs. PLA during ED relative to WM (P < 0.05). Changes in inflammatory, myogenic, and proteolytic gene expression did not differ between groups after exercise and recovery feeding. Mechanistic target of rapamycin signaling (i.e., translational efficiency) was also similar between groups at rest and after exercise and the mixed meal. Muscle total RNA content (i.e., translational capacity) increased more during ED in TEST than PLA (P < 0.05). These findings indicate that attenuated proteolysis at rest, possibly downstream of AR, Fn14, and IL-6R signaling, and increased translational capacity, not efficiency, may drive lean mass accretion with testosterone administration during energy deficit.

SUBMITTER: Howard EE

PROVIDER: S-EPMC7750513 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundSevere energy deficits cause interrelated reductions in testosterone and fat free mass. Testosterone supplementation may mitigate those decrements, but could also reduce circulating concentrations of the orexigenic hormone ghrelin, thereby exacerbating energy deficit by suppressing appetite.ObjectiveTo determine whether testosterone supplementation during severe energy deficit influences fasting and postprandial ghrelin concentrations and appetite.Design and methodsSecondary analysis of a randomized, double-blind trial that determined the effects of testosterone supplementation on body composition changes during and following severe energy deficit in nonobese, eugonadal men. Phase 1 (PRE-ED): 14-day run-in; phase 2: 28 days, 55% energy deficit with 200 mg testosterone enanthate weekly (TEST; n = 24) or placebo (PLA; n = 26); phase 3: free-living until body mass recovered (end-of-study; EOS). Fasting and postprandial acyl ghrelin and des-acyl ghrelin concentrations and appetite were secondary outcomes measured during the final week of each phase.ResultsFasting acyl ghrelin concentrations, and postprandial acyl and des-acyl ghrelin concentrations increased in PLA during energy deficit then returned to PRE-ED values by EOS, but did not change in TEST (phase-by-group, P < 0.05). Correlations between changes in free testosterone and changes in fasting acyl ghrelin concentrations during energy deficit (ρ = -0.42, P = 0.003) and body mass recovery (ρ = -0.38; P = 0.01) were not mediated by changes in body mass or body composition. Transient increases in appetite during energy deficit were not affected by testosterone treatment.ConclusionsTestosterone supplementation during short-term, severe energy deficit in healthy men prevents deficit-induced increases in circulating ghrelin without blunting concomitant increases in appetite.Clinical trials registrationwww.clinicaltrials.gov NCT02734238 (registered 12 April 2016).

Project description:The objective of this study was to determine metabolic and physiological differences between males with low testosterone (LT) versus those with normal testosterone (NT) following a period of severe energy deficit. In this secondary analysis, 68 male US Marines (mean ± SD, 24.6 ± 2.4 y) were dichotomized by testosterone concentration (< or ≥ 10.5 nmol/L as determined from a single blood sample collected between 0600-0630 after an 8-10 h overnight fast by automated immunoassay) following 7 days of near complete starvation (~300 kcal consumed/d, ~85% energy deficit) during Survival, Evasion, Resistance, and Escape (SERE) training. Dietary intake was assessed before (PRE) SERE. Body composition (dual-energy x-ray absorptiometry and peripheral quantitative computed tomography) and whole-body protein turnover (15 N alanine) were assessed before (PRE) and after (POST) SERE. Mean testosterone concentrations decreased PRE (17.5 ± 4.7 nmol/L) to POST (9.8 ± 4.0 nmol/L, p < 0.0001). When volunteers were dichotomized by POST testosterone concentrations [NT (n = 24) 14.1 ± 3.4 vs. LT (n = 44): 7.5 ± 1.8 nmol/L, p < 0.0001], PRE BMI, total fat mass, trunk fat mass, and testosterone were greater and the diet quality score and total carbohydrate intake were lower in NT compared to LT (p ≤ 0.05). LT lost more fat-free mass and less fat mass, particularly in the trunk region, compared to NT following SERE (p-interaction≤0.044). Whole-body protein synthesis, net balance, and flux decreased and whole-body protein breakdown increased from PRE to POST in both groups (p-time ≤0.025). Following short-term, severe energy deficit, Marines who exhibited low testosterone had greater fat-free mass loss than those who maintained normal testosterone concentrations. Altering body composition and dietary strategies prior to physical training that elicits severe energy deficit may provide an opportunity to attenuate post-training decrements in testosterone and its associated effects (e.g., loss of lean mass, performance declines, fatigue).

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Testosterone supplementation upregulates androgen receptor expression and translational capacity during severe energy deficit.

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