Effects of Aerobic Exercise Training on C1q Tumor Necrosis Factor α-Related Protein Isoform 5 (Myonectin): Association with Insulin Resistance and Mitochondrial DNA Density in Women

Context: The C1q TNF alpha-related protein (C1QTNF) families exhibit a C-terminal complement factor C1q globular domain similar to that of TNF. However, their clinical implications are largely unknown. We recently found that the C1q TNF alpha-related protein isoform 5 (C1QTNF5 or myonectin) level was increased in insulin-resistant rodents and mitochondrial DNA (mtDNA)-depleted myocytes. Objective: We aimed to determine the effects of aerobic exercise training on C1QTNF5 level and its association with insulin resistance and mtDNA density in young and old healthy women. Design and Setting: Fourteen healthy young women aged 22.5 +/- 2.7 yr and 14 healthy older women aged 60.3 +/- 5.2 yr performed aerobic exercise at 60-80% of maximal oxygen consumption (VO(2)max) over three 1-h sessions per week for 10 wk. Insulin resistance was assessed by homeostasis model assessment of insulin resistance and adiponectin concentration. Serum C1QTNF5 level was estimated by immunoblotting. The mtDNA/28S rRNA ratio was used to determine mtDNA density. Results: VO(2)max increased significantly after the exercise training from 33.1 +/- 6.2 to 35.3 +/- 5.3 ml/kg . min in younger women and from 23.2 +/- 3.1 to 27.2 +/- 4.8 ml/kg . min in older women (P < 0.05). The C1QTNF5 level and homeostasis model assessment of insulin resistance decreased significantly after exercise training and were correlated positively (r = 0.462; P < 0.01). There were negative correlations between the changes in C1QTNF5 level and the changes in VO(2)max, mtDNA density, and adiponectin level (r = -0.495, -0.672, and -0.569, respectively; all P < 0.01). Conclusion: These findings suggest a physiological function for C1QTNF5 (myonectin) in linking insulin resistance with quantitative changes in mtDNA. Further research exploring the role of C1QTNF5 in the development of insulin resistance is warranted. (J Clin Endocrinol Metab 97: E88-E93, 2012)