Mitochondria, glycogen, and lipid droplets in skeletal muscle during testosterone treatment and strength training: a randomized, double‐blinded, placebo‐controlled trial

Abstract

Low testosterone levels in aging men are associated with insulin resistance. Mitochondrial dysfunction, changes in glycogen metabolism, and lipid accumulation are linked to insulin resistance in skeletal muscle. In this randomized, double-blinded, placebo-controlled study, we investigated the effects of six-month testosterone replacement therapy (TRT) and strength training (ST) on mitochondrial, glycogen, and lipid droplet (LD) content in skeletal muscle of aging men with subnormal bioavailable testosterone (BioT) levels. Mitochondrial, glycogen, and LD volume fractions in muscle biopsies were estimated by transmission electron microscopy. Insulin sensitivity (insulin-stimulated Rd) and body composition were assessed by euglycemic-hyperinsulinemic clamp and dual X-ray absorptiometry, respectively. TRT significantly increased total testosterone levels, BioT, and lean body mass (LBM) (p < 0.05), whereas percent body fat decreased (p < 0.05), and insulin sensitivity was unchanged. Baseline mitochondrial volume fraction correlated inversely with percent body fat (ρ = -0.43; p = 0.003). Δ-mitochondrial fraction correlated positively with Δ-total testosterone (ρ = 0.70; p = 0.02), and Δ-glycogen fraction correlated inversely with Δ-LBM (ρ = -0.83; p = 0.002) during six-month TRT, but no significant changes were observed in mitochondrial, glycogen, and LD volume fractions during TRT and ST. In conclusion, in this exploratory small-scale study, the beneficial effects of six-month TRT on total testosterone, LBM, and percent body fat were not followed by significant changes in fractions of mitochondria, glycogen, or lipid in skeletal muscle of aging men with lowered testosterone levels. Six-month ST or combined three-month ST+TRT did not change intramyocellular mitochondria, glycogen, and LD fractions compared to placebo. However, further studies with a larger sample size are needed.

Testosterone treatment is associated with reduced adipose tissue dysfunction and nonalcoholic fatty liver disease in obese hypogonadal men

“…Our data also corroborated the pivotal role of T in maintaining the homeostasis of mitochondria, the most energetically active organelles in the eukaryotic cells [85]. Previous studies, both in animal models and in humans, demonstrated that androgens stimulate glucose utilization and ATP production, as well as mitochondrial cytochrome c oxidase activity in muscle [86][87][88], and in several other tissues and cell types [89][90][91][92]. However, to our knowledge, this is the first demonstration that in vivo TTh is associated with a healthier phenotype of human preadipocytes.…”

Amino acid and fatty acid metabolomic profile during fasting and hyperinsulinemia in girls with polycystic ovarian syndrome

“…This is consistent with evidence demonstrating increased whole body lipid oxidation in hypogonadic men treated with testosterone (42). Whereas increases in the proportion of the mitochondrial fraction of the muscle cell related to increases in serum testosterone, there was no apparent change in the number or activity of mitochondrial enzymes, genes involved in biogenesis, or lipid metabolism (24,42). Thus the exact role of excess or supplemental testosterone in mitochondrial function per se remains unclear.…”

The Prevalence of Hypogonadism and the Effectiveness of Androgen Administration on Body Composition in HIV-Infected Men: A Meta-Analysis

“…Thus, despite these significant variations in serum hormonal levels, the biochemical mechanism by which Te affects body composition is not completely understood. The androgens' capability to increase LBM, and consequently muscle mass, has been previously envisaged in different experimental settings [62,63]. In fact, Te is able to stimulate lipolysis in animal models [64], as well as in human subcutaneous adipose tissue, in which both a Te-induced inhibition of lipoprotein lipase and an activation of the hormone sensitive lipase were observed [65].…”