Mechanisms for fiber-type specificity of skeletal muscle atrophy

Curr Opin Clin Nutr Metab Care. 2013 May;16(3):243-50. doi: 10.1097/MCO.0b013e328360272d.


Purpose of review: There are a variety of pathophysiologic conditions that are known to induce skeletal muscle atrophy. However, muscle wasting can occur through multiple distinct signaling pathways with differential sensitivity between selective skeletal muscle fiber subtypes. This review summarizes some of the underlying molecular mechanisms responsible for fiber-specific muscle mass regulation.

Recent findings: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha protects slow-twitch oxidative fibers from denervation/immobilization (disuse)-induced muscle atrophies. Nutrient-related muscle atrophies, such as those induced by cancer cachexia, sepsis, chronic heart failure, or diabetes, are largely restricted to fast-twitch glycolytic fibers, of which the underlying mechanism is usually related to abnormality of protein degradation, including proteasomal and lysosomal pathways. In contrast, nuclear factor kappaB activation apparently serves a dual function by inducing both fast-twitch fiber atrophy and slow-twitch fiber degeneration.

Summary: Fast-twitch glycolytic fibers are more vulnerable than slow-twitch oxidative fibers under a variety of atrophic conditions related to signaling transduction of Forkhead box O family, autophagy inhibition, transforming growth factor beta family, and nuclear factor-kappaB. The resistance of oxidative fibers may result from the protection of peroxisome proliferator-activated receptor gamma coactivator 1-alpha.

Publication types

  • Review

MeSH terms

  • Animals
  • Cachexia / complications
  • Cachexia / pathology
  • Chronic Disease
  • Diabetes Mellitus / pathology
  • Disease Models, Animal
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Glycolysis
  • Heart Diseases / complications
  • Heart Diseases / pathology
  • Humans
  • Muscle Fibers, Fast-Twitch / metabolism
  • Muscle Fibers, Fast-Twitch / pathology*
  • Muscle Fibers, Slow-Twitch / metabolism
  • Muscle Fibers, Slow-Twitch / pathology*
  • Muscular Atrophy / pathology*
  • Muscular Diseases / metabolism
  • Muscular Diseases / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Sepsis / complications
  • Sepsis / pathology
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • NF-kappa B
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • Transforming Growth Factor beta