{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T15:43:26Z","timestamp":1788623006617,"version":"build-2803163510"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction-Associated Steatohepatitis (MASH) is a progressive subtype of Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) characterized by hepatic steatosis, inflammation, hepatocellular injury, and fibrosis, which may evolve to cirrhosis and hepatocellular carcinoma. Despite its growing global burden, no widely approved pharmacotherapy is available, highlighting the need to elucidate immunometabolic mechanisms and identify effective therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Content<\/jats:title>\n                    <jats:p>This review summarizes the epidemiology and clinical features of MASH and focuses on key pathogenic pathways, including insulin resistance, lipotoxicity, mitochondrial dysfunction, and gut-liver axis disturbance. Immune dysregulation mediated by Kupffer cell activation, macrophage polarization, inflammasome signaling, and cytokine networks is discussed in depth. The critical role of immunometabolic crosstalk in disease progression is emphasized. Current and emerging therapeutic targets\u2014such as PPARs, FXR, THR-\u03b2, the GLP-1\/FGF21 axis, DGAT2, and CCR2\/CCR5\u2014are systematically reviewed, together with advances in oligonucleotide therapy, cell-based interventions, and combination strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MASH results from the complex coupling of metabolic imbalance and immune-driven inflammation, making single-target therapy insufficient. Precision stratification based on immunometabolic networks and multi-target interventions represent promising directions for future drug development and individualized treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1801906","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:44:02Z","timestamp":1779252242000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The immunometabolic mechanisms and therapeutic targets of metabolic dysfunction-associated steatohepatitis"],"prefix":"10.3389","volume":"13","author":[{"given":"Jiang","family":"Yu","sequence":"first","affiliation":[{"name":"Department of General Surgery, The Second Clinical Medical College, North Sichuan Medical College, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Clinical Medical College, North Sichuan Medical College, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1016\/S0140-6736(24)01811-7","article-title":"Steatotic liver disease","volume":"404","author":"Israelsen","year":"2024","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1001\/jama.2025.19615","article-title":"Metabolic dysfunction-associated steatotic liver disease in adults: a 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