Department of Health and Kinesiology and Max E, Wastl Human Performance Laboratory, Purdue University, 800 W. Stadium Ave, West Lafayette, IN, 47907, USA.
Department of Animal Sciences, Purdue University, West Lafayette, IN, USA.
Eur J Appl Physiol. 2020 Dec;120(12):2835-2846. doi: 10.1007/s00421-020-04509-z. Epub 2020 Sep 28.
Obesity is associated with numerous changes in skeletal muscle including greater muscle mass and muscle fiber cross sectional area (FCSA), yet fasted muscle protein synthesis is lower. Activation of the IGF-1/Akt/mTOR pathway is critical for muscle mass maintenance, muscle hypertrophy, and muscle protein regulation. Resistance exercise (RE) increases muscle mass, FCSA, and IGF-1. Persons with obesity have greater skeletal muscle mass and larger skeletal muscle fiber cross sectional area. The IGF-1/Akt/mTOR pathway is critical for the regulation of skeletal muscle mass. Our study found men and women with obesity have lower skeletal muscle IGF-1 mRNA and protein and higher expression of miR-206 an epigenetic regulator of IGF-1, at rest and following an acute bout of resistance exercise. Despite this, Akt mediated signaling was maintained and maintenance of phosphorylation does not appear to be accounted for by compensatory pathways. Our findings suggest a possible negative feedback mechanism via increased miR-206 and in turn decreased IGF-1 to limit further skeletal muscle hypertrophy in persons with obesity. The current work investigated if: (1) obesity dysregulates basal skeletal muscle IGF-1 pathways; and (2) obesity augments the muscle IGF-1 pathway responses to acute RE.
Eight sedentary (no self-reported physical activity), lean (LN) and eight sedentary subjects with obesity (OB) had vastus lateralis biopsies taken at rest, and 15 min and 3 h post-acute RE for the measurement of the IGF-1 pathway and muscle FCSA.
Type II FCSA was larger in OB vs. LN. Skeletal muscle IGF-1 mRNA and IGF-1 protein were lower in OB vs. LN at rest and post-exercise. Acute RE increased IGF-1 protein similarly in both groups. The expression of miR-206, a post-transcriptional inhibitor of IGF-1 expression, was higher in OB vs. LN and linked with lower IGF-1 mRNA (r = - 0.54).
In spite of greater muscle FCSA, muscle IGF-1 expression was lower in obesity suggesting negative feedback may be limiting muscle mass expansion in obesity.
肥胖与骨骼肌的许多变化有关，包括更大的肌肉质量和肌肉纤维横截面积（FCSA），但空腹肌肉蛋白质合成较低。IGF-1/Akt/mTOR 通路的激活对于维持肌肉质量、肌肉肥大和肌肉蛋白调节至关重要。阻力运动（RE）增加肌肉质量、FCSA 和 IGF-1。肥胖者的骨骼肌质量更大，骨骼肌纤维横截面积更大。IGF-1/Akt/mTOR 通路对于调节骨骼肌质量至关重要。我们的研究发现，肥胖男性和女性在休息时和急性抵抗运动后，骨骼肌 IGF-1 mRNA 和蛋白水平较低，miR-206 表达较高，miR-206 是 IGF-1 的一种表观遗传调节剂。尽管如此，Akt 介导的信号仍然存在，磷酸化的维持似乎不是由补偿途径引起的。我们的研究结果表明，肥胖个体可能通过增加 miR-206 并随之降低 IGF-1 来限制进一步的骨骼肌肥大，从而产生一种负反馈机制。目前的工作研究了以下问题：（1）肥胖是否会调节基础骨骼肌 IGF-1 通路；（2）肥胖是否会增强肌肉 IGF-1 通路对急性 RE 的反应。
8 名久坐（无自我报告的体育活动）、瘦（LN）和 8 名久坐肥胖（OB）受试者在休息时、急性 RE 后 15 分钟和 3 小时取股外侧肌活检，以测量 IGF-1 通路和肌肉 FCSA。
OB 组的 II 型 FCSA 大于 LN 组。OB 组在休息和运动后，骨骼肌 IGF-1 mRNA 和 IGF-1 蛋白均低于 LN 组。急性 RE 同样增加了两组的 IGF-1 蛋白。IGF-1 表达的转录后抑制剂 miR-206 在 OB 组中的表达高于 LN 组，与 IGF-1 mRNA 呈负相关（r=-0.54）。
尽管肌肉 FCSA 更大，但肥胖患者的肌肉 IGF-1 表达较低，这表明负反馈可能限制了肥胖患者的肌肉质量扩张。
