Department of Endocrinology, Odense University Hospital, Odense C, Denmark.
Department of Sports Science & Clinical Biomechanics, University of Southern Denmark, Odense M, Denmark.
Andrology. 2018 Jul;6(4):547-555. doi: 10.1111/andr.12492. Epub 2018 Apr 15.
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.
衰老男性的低睾酮水平与胰岛素抵抗有关。线粒体功能障碍、糖原代谢变化和脂质积累与骨骼肌胰岛素抵抗有关。在这项随机、双盲、安慰剂对照研究中，我们研究了六个月的睾酮替代治疗 (TRT) 和力量训练 (ST) 对生物可利用睾酮 (BioT) 水平降低的衰老男性骨骼肌中线粒体、糖原和脂滴 (LD) 含量的影响。通过透射电子显微镜估计肌肉活检中的线粒体、糖原和 LD 体积分数。通过正葡萄糖高胰岛素钳夹和双能 X 射线吸收法分别评估胰岛素敏感性 (胰岛素刺激的 Rd) 和身体成分。TRT 显著增加总睾酮水平、BioT 和瘦体重 (LBM) (p<0.05)，而体脂百分比降低 (p<0.05)，胰岛素敏感性不变。基线线粒体体积分数与体脂百分比呈负相关 (ρ=-0.43；p=0.003)。Δ-线粒体分数与 Δ-总睾酮呈正相关 (ρ=0.70；p=0.02)，Δ-糖原分数与 Δ-LBM 呈负相关 (ρ=-0.83；p=0.002) 在六个月的 TRT 期间，但在 TRT 和 ST 期间，线粒体、糖原和 LD 体积分数没有观察到显著变化。总之，在这项小规模探索性研究中，六个月 TRT 对总睾酮、LBM 和体脂百分比的有益影响并未导致降低睾酮水平的衰老男性骨骼肌中线粒体、糖原和脂质的分数发生显著变化。与安慰剂相比，六个月的 ST 或联合三个月的 ST+TRT 并没有改变肌内线粒体、糖原和 LD 分数。然而，需要更大样本量的进一步研究。
