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However, therapeutic targeting of these skeletal muscle mechanisms has not advanced the prevention of critical illness-induced muscle wasting, which may require exploring the roles of other peripheral organs. For example, recent research has demonstrated positive associations between whole-body adipose tissue mass, maintenance of muscle mass, and lower mortality rates in critically ill patients. However, having excess adiposity is often associated with impaired skeletal muscle remodeling due to blunted anabolic signaling, which has been tied to insulin resistance, lipid accumulation, and inflammation. Thus, the positive association between adiposity and beneficial outcomes in critical illness is paradoxical. This may be explained, at least partially, by an incomplete understanding of the processes by which adipose tissue influences skeletal muscle health and function in the context of critical illness. This review highlights the current evidence and key questions that warrant further investigations to improve understanding of the relationship between adipose tissue and skeletal muscle health. This knowledge may then be leveraged to facilitate new therapeutic approaches aimed at improving skeletal muscle health and functional outcomes in patients with critical illness.<\/jats:p>","DOI":"10.1152\/japplphysiol.00203.2025","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T21:21:00Z","timestamp":1751318460000},"page":"414-437","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The role of adipose tissue in critical illness-induced skeletal muscle wasting\u2014new considerations for treatment approaches"],"prefix":"10.1152","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7719-717X","authenticated-orcid":false,"given":"Casey L.","family":"Sexton","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Alabama at Birmingham","place":["United 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