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Here, we identify the Nogo-B receptor (NgBR; NUS1) as a regulator of hepatic adiponectin sensitivity. Across human, cynomolgus monkey, and mouse datasets, hepatic NgBR expression is consistently reduced in obesity-associated diabetes, indicating a conserved metabolic signature. Hepatocyte-specific NgBR deletion abolishes the metabolic effects of the adiponectin agonist AdipoRon, resulting in impaired AMPK activation, persistent gluconeogenesis, and ceramide accumulation. Mechanistically, NgBR loss suppresses KAT7 expression and reduces histone acetylation at AdipoR1 and AdipoR2 promoters, thereby limiting receptor expression. Adeno-associated virus (AAV)-mediated restoration of hepatic NgBR reinstates KAT7-dependent chromatin activation, adiponectin receptor expression, and glucose homeostasis. These findings support a hepatocellular mechanism in which NgBR maintains adiponectin receptor competence and suggest a potential therapeutic strategy for restoring adiponectin responsiveness in metabolic disease.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Graphical Abstract<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"726643v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.20.726643","type":"posted-content","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T06:30:23Z","timestamp":1779517823000},"source":"Crossref","is-referenced-by-count":0,"title":["NgBR controls hepatic adiponectin signaling competence through KAT7-dependent chromatin regulation"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-646X","authenticated-orcid":false,"given":"Mohammad Sarif","family":"Mohiuddin","sequence":"first","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munichandra Babu","family":"Tirumalasetty","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenquan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"},{"name":"Center for Lipid Research & Key Laboratory of Molecular Biology for Infectious Diseases, Institute for Viral Hepatitis, Department of Infectious Diseases, the Second Affiliated Hospital, Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-2551","authenticated-orcid":false,"given":"Rashu","family":"Barua","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5915-8935","authenticated-orcid":false,"given":"Md.","family":"Wahiduzzaman","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2350-0855","authenticated-orcid":false,"given":"Mayank","family":"Choubey","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0446-5553","authenticated-orcid":false,"given":"Gary J.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Diabetes Research Center: Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-1238","authenticated-orcid":false,"given":"Qing Robert","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Foundations of Medicine, New York University Grossman Long Island School of Medicine, Mineola, NY, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026052609250844000_2026.05.20.726643v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01301-6"},{"key":"2026052609250844000_2026.05.20.726643v1.2","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1016\/S0140-6736(23)01296-5","article-title":"Diabetes: a defining disease of the 21st century","volume":"401","year":"2023","journal-title":"Lancet"},{"key":"2026052609250844000_2026.05.20.726643v1.3","doi-asserted-by":"crossref","unstructured":"Sun, H. , et al. 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