Differential effects of pre-exercise on cancer cachexia-induced muscle atrophy in fast- and slow-twitch muscles

FASEB J. 2020 Nov;34(11):14389-14406. doi: 10.1096/fj.202001330R. Epub 2020 Sep 5.

Abstract

We hypothesized that pre-exercise may effectively prevent cancer cachexia-induced muscle atrophy in both fast- and slow-twitch muscle types. Additionally, the fast-twitch muscle may be more affected by cancer cachexia than slow-twitch muscle. This study aimed to evaluate the effects of pre-exercise on cancer cachexia-induced atrophy and on atrophy in fast- and slow-twitch muscles. Twelve male Wistar rats were randomly divided into sedentary and exercise groups, and another 24 rats were randomly divided into control, pre-exercise, cancer cachexia induced by intraperitoneal injections of ascites hepatoma AH130 cells, and pre-exercise plus cancer cachexia groups. We analyzed changes in muscle mass and in gene and protein expression levels of major regulators and indicators of muscle protein degradation and synthesis pathways, angiogenic factors, and mitochondrial function in both the plantaris and soleus muscles. Pre-exercise inhibited muscle mass loss, rescued protein synthesis, prevented capillary regression, and suppressed hypoxia in the plantaris and soleus muscles. Pre-exercise inhibited mitochondrial dysfunction differently in fast- and slow-twitch muscles. These results suggested that pre-exercise has the potential to inhibit cancer-cachexia-induced muscle atrophy in both fast- and slow-twitch muscles. Furthermore, the different progressions of cancer-cachexia-induced muscle atrophy in fast- and slow-twitch muscles are related to differences in mitochondrial function.

Keywords: cancer cachexia; muscle atrophy; pre-exercise; protein degradation; protein synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cachexia / etiology
  • Cachexia / prevention & control*
  • Cell Line, Tumor
  • Male
  • Mitochondria, Muscle / metabolism
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Fast-Twitch / physiology*
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / physiology*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / prevention & control*
  • Neoplasms, Experimental / complications
  • Neovascularization, Physiologic
  • Physical Conditioning, Animal / methods*
  • Protein Biosynthesis
  • Rats
  • Rats, Wistar