{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:01:32Z","timestamp":1791475292635,"version":"4.3.4"},"reference-count":196,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T00:00:00Z","timestamp":1603929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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., PPAR\u03b1, -\u03b2\/\u03b4, and -\u03b3. The expression of PPAR\u03b1 is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPAR\u03b2\/\u03b4 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 PPAR\u03b3 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\u2013muscle 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.<\/jats:p>","DOI":"10.3390\/ijms21218056","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T09:44:53Z","timestamp":1603964693000},"page":"8056","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["PPARs and Microbiota in Skeletal Muscle Health and Wasting"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1240-2771","authenticated-orcid":false,"given":"Ravikumar","family":"Manickam","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7455-6090","authenticated-orcid":false,"given":"Kalina","family":"Duszka","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5966-9089","authenticated-orcid":false,"given":"Walter","family":"Wahli","sequence":"additional","affiliation":[{"name":"Center for Integrative Genomics, University of Lausanne, Le G\u00e9nopode, CH-1015 Lausanne, Switzerland"},{"name":"Toxalim, INRAE, Chemin de Tournefeuille 180, F-31027 Toulouse, France"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Clinical Sciences Building, 11 Mandalay Road, Singapore 308232, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1152\/jappl.2000.89.2.465","article-title":"Estimation of skeletal muscle mass by bioelectrical impedance analysis","volume":"89","author":"Janssen","year":"2000","journal-title":"J. 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