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PPARs and Microbiota in Skeletal Muscle Health and Wasting

Department of Pharmaceutical Sciences, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA
Department of Nutritional Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria
Center for Integrative Genomics, University of Lausanne, Le Génopode, CH-1015 Lausanne, Switzerland
Toxalim, INRAE, Chemin de Tournefeuille 180, F-31027 Toulouse, France
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, Singapore 308232, Singapore
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(21), 8056;
Received: 18 October 2020 / Revised: 24 October 2020 / Accepted: 26 October 2020 / Published: 29 October 2020
(This article belongs to the Special Issue Muscle Atrophy: Discovery of Mechanisms and Potential Therapies)
Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -β/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARβ/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut–muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting. View Full-Text
Keywords: PPAR; muscle; microbiota; gut; metabolism PPAR; muscle; microbiota; gut; metabolism
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MDPI and ACS Style

Manickam, R.; Duszka, K.; Wahli, W. PPARs and Microbiota in Skeletal Muscle Health and Wasting. Int. J. Mol. Sci. 2020, 21, 8056.

AMA Style

Manickam R, Duszka K, Wahli W. PPARs and Microbiota in Skeletal Muscle Health and Wasting. International Journal of Molecular Sciences. 2020; 21(21):8056.

Chicago/Turabian Style

Manickam, Ravikumar, Kalina Duszka, and Walter Wahli. 2020. "PPARs and Microbiota in Skeletal Muscle Health and Wasting" International Journal of Molecular Sciences 21, no. 21: 8056.

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