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Adipose tissue dysfunction is emerging as a driving factor in the transition from excess adiposity to comorbidities such as metabolic-associated fatty liver disease, cardiovascular disease, Type 2 diabetes and cancer. However, the transition from healthy adipose expansion to the development of these conditions is poorly understood. Adipose stem cells, residing in the vasculature and stromal regions of subcutaneous and visceral depots, are responsible for the expansion and maintenance of organ function, and are now recognised as key mediators of pathological transformation. Impaired tissue expansion drives inflammation, dysregulation of endocrine function and the deposition of lipids in the liver, muscle and around vital organs, where it is toxic. Contrary to previous hypotheses, it is the promotion of healthy adipose tissue expansion and function, not inhibition of adipogenesis, that presents the most attractive therapeutic strategy in the treatment of metabolic disease. AMP-activated protein kinase, a master regulator of energy homeostasis, has been regarded as one such target, due to its central role in adipose tissue lipid metabolism, and its apparent inhibition of adipogenesis. However, recent studies utilising AMP-activated protein kinase (AMPK)-specific compounds highlight a more subtle, time-dependent role for AMPK in the process of adipogenesis, and in a previously unexplored repression of leptin, independent of adipocyte maturity. In this article, I discuss historic evidence for AMPK-mediated adipogenesis inhibition and the multi-faceted roles for AMPK in adipose tissue.<\/jats:p>","DOI":"10.1042\/ebc20240008","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T06:56:25Z","timestamp":1724396185000},"page":"349-361","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["New concepts in the roles of AMPK in adipocyte stem cell biology"],"prefix":"10.1042","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5049-3761","authenticated-orcid":false,"given":"Alice\u00a0E.","family":"Pollard","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,11,18]]},"reference":[{"key":"2024111809363890800_B1","article-title":"World Obesity Atlas 2023","author":"Federation WO","year":"2023"},{"key":"2024111809363890800_B2","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N. 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