ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026
Hepatocyte CBX2 Safeguards Hepatic Lipid Homeostasis by Elevating Ca
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately one-third of adults and lacks effective pharmacological therapies. Here, we identify Chromobox 2 (CBX2), a Polycomb-associated chromatin regulator, as a previously unrecognized regulator of hepatic lipid homeostasis. CBX2 expression is markedly reduced in hepatocytes from patients with MASLD, multiple mouse models (db/db, ob/ob, HFD, and HFHC), and steatotic hepatocytes in vitro. Hepatocyte-specific CBX2 overexpression ameliorates hepatic steatosis, improves glucose metabolism, and suppresses inflammation, whereas CBX2 deficiency exacerbates these metabolic disturbances. Mechanistically, CBX2 enhances H3K4me3 enrichment at the Orai1 promoter, promoting Orai1 transcription and increasing intracellular Ca
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