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Mechanisms for fiber-type specificity of skeletal muscle atrophy

Wang, Yichen; Pessin, Jeffrey E.

Current Opinion in Clinical Nutrition & Metabolic Care: May 2013 - Volume 16 - Issue 3 - p 243–250
doi: 10.1097/MCO.0b013e328360272d
TRANSLATIONAL RESEARCH IN WASTING DISEASES: Edited by Vickie E. Baracos, Didier Attaix and Claude Pichard

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.

aDepartment of Molecular Pharmacology

bDepartment of Medicine, Albert Einstein College of Medicine, Diabetes Research and Training Center, Bronx, New York, USA

Correspondence to Jeffrey E. Pessin, PhD, Judy R. & Alfred A. Rosenberg Professorial, Chair in Diabetes Research, Director, Diabetes Research Center, Departments of Medicine and Molecular Pharmacology, Albert Einstein College of Medicine, 1301 Morris Park Avenue, Bronx, NY 10461, USA. Tel: +1 718 678 1029; fax: +1 718 678 1020; e-mail:

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