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This review synthesizes the current evidence from human studies on autophagy alterations under these metabolic conditions. In obesity, most data point to autophagy upregulation during the initiation phase of autophagosome formation, potentially in response to proinflammatory conditions in the adipose tissue. Autophagosome formation appears to be enhanced under hyperglycemic or insulin-resistant conditions in patients with T2D, possibly acting as a compensatory mechanism to eliminate damaged organelles and proteins. Other studies have proposed that prolonged hyperglycemia and disrupted insulin signaling hinder autophagic flux, resulting in the accumulation of dysfunctional cellular components that can contribute to \u03b2-cell dysfunction. Evidence from patients with MASLD supports autophagy inhibition in disease progression. Nevertheless, given the available data, it is difficult to ascertain whether autophagy is enhanced or suppressed in these conditions because the levels of autophagy markers depend on the overall metabolism of specific organs, tissues, experimental conditions, or disease duration. Owing to these constraints, determining whether the observed shifts in autophagic activity precede or result from metabolic diseases remains challenging. Additionally, autophagy-modulating strategies are shortly discussed. To conclude, more studies investigating autophagy impairment are required to gain a more comprehensive understanding of its role in the pathogenesis of obesity, T2D, and MASLD and to unveil novel therapeutic strategies for these conditions.<\/jats:p>","DOI":"10.1007\/s11739-024-03700-w","type":"journal-article","created":{"date-parts":[[2024,7,6]],"date-time":"2024-07-06T15:01:47Z","timestamp":1720278107000},"page":"1473-1491","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Autophagy alterations in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease: the evidence from human studies"],"prefix":"10.1007","volume":"19","author":[{"given":"Patrycja","family":"Jakubek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Pakula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Rossmeisl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Pinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Rimessi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0789-4521","authenticated-orcid":false,"given":"Mariusz Roman","family":"Wieckowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,6]]},"reference":[{"key":"3700_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","volume":"7","author":"K Riazi","year":"2022","unstructured":"Riazi K, Azhari H, Charette JH, Underwood FE, King JA, Afshar EE, Swain MG, Congly SE, Kaplan GG, Shaheen AA (2022) The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis. 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