Acute endurance exercise stimulates circulating levels of mitochondrial-derived peptides in humans

J Appl Physiol (1985). 2021 Sep 1;131(3):1035-1042. doi: 10.1152/japplphysiol.00706.2019. Epub 2021 Aug 5.

Abstract

Mitochondrial-derived peptides (MDPs) humanin (HN) and mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) are involved in cell survival, suppression of apoptosis, and metabolism. Circulating levels of MDPs are altered in chronic diseases such as diabetes type 2 and chronic kidney disease. Whether acute resistance (RE) or endurance (EE) exercise modulates circulating levels of HN and MOTS-c in humans is unknown. Following familiarization, subjects were randomized to EE (n = 10, 45 min cycling at 70% of estimated V̇O2max), RE (n = 10, 4 sets × 7RM, leg press and knee extension), or control (CON, n = 10). Skeletal muscle biopsies and blood samples were collected before and at 30 min and 3 h following exercise. Plasma concentration of HN and MOTS-c, skeletal muscle MOTS-c as well as gene expression of exercise-related genes were analyzed. Acute EE and RE promoted changes in skeletal muscle gene expression typically seen in response to each exercise modality (c-Myc, 45S pre-rRNA, PGC-1α-total, and PGC-1α-ex1b). At rest, circulating levels of HN were positively correlated to MOTS-c levels and age. Plasma levels of MDPs were not correlated to fitness outcomes [V̇O2max, leg strength, or muscle mitochondrial (mt) DNA copy number]. Circulating levels of HN were significantly elevated by acute EE but not RE. MOTS-C levels showed a trend to increase after EE. These results indicate that plasma MDP levels are not related to fitness status but that acute EE increases circulating levels of MDPs, in particular HN.NEW & NOTEWORTHY In this manuscript, we report for the first time, to our knowledge, the response of circulating levels of mitochondrial-derived peptides humanin and MOTS-c to acute resistance and endurance exercise. Our data support that acute endurance exercise stimulates MDP levels in plasma, whereas acute resistance exercise does not.

Keywords: MOTS-c; exercise; humanin; mitochondria; skeletal muscle.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exercise
  • Humans
  • Mitochondria*
  • Muscle, Skeletal / metabolism
  • Peptides*
  • Transcription Factors / metabolism

Substances

  • Peptides
  • Transcription Factors

Associated data

  • figshare/10.6084/m9.figshare.15034692.v1