Seminars in Immunopathology

, Volume 36, Issue 1, pp 27–53 | Cite as

Functional crosstalk of PGC-1 coactivators and inflammation in skeletal muscle pathophysiology

Review

Abstract

Skeletal muscle is an organ involved in whole body movement and energy metabolism with the ability to dynamically adapt to different states of (dis-)use. At a molecular level, the peroxisome proliferator-activated receptor γ coactivators 1 (PGC-1s) are important mediators of oxidative metabolism in skeletal muscle and in other organs. Musculoskeletal disorders as well as obesity and its sequelae are associated with PGC-1 dysregulation in muscle with a concomitant local or systemic inflammatory reaction. In this review, we outline the function of PGC-1 coactivators in physiological and pathological conditions as well as the complex interplay of metabolic dysregulation and inflammation in obesity with special focus on skeletal muscle. We further put forward the hypothesis that, in this tissue, oxidative metabolism and inflammatory processes mutually antagonize each other. The nuclear factor κB (NF-κB) pathway thereby plays a key role in linking metabolic and inflammatory programs in muscle cells. We conclude this review with a perspective about the consequences of such a negative crosstalk on the immune system and the possibilities this opens for clinical applications.

Keywords

Skeletal muscle Metabolism Metabolic disorders Inflammation PGC-1 NF-κB Macrophages 

Notes

Acknowledgments

This review is dedicated to the memory of Dr. Martine Christe. Research in our laboratory is supported by the Swiss National Science Foundation, the Muscular Dystrophy Association USA (MDA), the SwissLife ‘Jubiläumsstiftung für Volksgesundheit und medizinische Forschung’, the Swiss Society for Research on Muscle Diseases (SSEM), the Swiss Diabetes Association, the Roche Research Foundation, the United Mitochondrial Disease Foundation (UMDF), the Association Française contre les Myopathies (AFM), the Gebert-Rüf Foundation “Rare Diseases” Program, the University of Basel, and the Biozentrum.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Biozentrum, University of BaselBaselSwitzerland

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