{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:55:02Z","timestamp":1790794502515,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Clinical Investigation","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82270904"],"award-info":[{"award-number":["82270904"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82300601"],"award-info":[{"award-number":["82300601"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82270904"],"award-info":[{"award-number":["82270904"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Natural Science Foundation of China","award":["82300601"],"award-info":[{"award-number":["82300601"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>\n                    Intestinal lipid metabolism is essential for systemic energy homeostasis, and its modulation is emerging as a therapeutic strategy for obesity. Menin, encoded by the\n                    <jats:italic>MEN1<\/jats:italic>\n                    gene, is a scaffold protein that regulates chromatin remodeling and gene expression and is abundantly expressed in intestinal epithelial cells (IECs), but its metabolic role remains underexplored. Here, we generated IEC-specific\n                    <jats:italic>Men1<\/jats:italic>\n                    -knockout mice and found that\n                    <jats:italic>Men1<\/jats:italic>\n                    deficiency protected against high-fat diet\u2013induced obesity, accompanied by elevated carboxylesterase 1 (CES1) expression in IECs. Increased CES1 promoted triglyceride (TG) hydrolysis and reduced intracellular TG storage, thereby limiting the lipid substrate pool required for ApoB48-dependent chylomicron assembly. Although lipid hydrolysis was enhanced, steady-state free fatty acid levels were not increased; instead,\n                    <jats:italic>Men1<\/jats:italic>\n                    deficiency activated fatty acid \u03b2-oxidation programs and increased etomoxir-sensitive fatty acid\u2013dependent mitochondrial respiration, supporting enhanced fatty acid catabolism. Mechanistically, menin recruited histone deacetylase 1 and interacted with the nuclear receptor liver X receptor-\u03b2 to suppress\n                    <jats:italic>Ces1g<\/jats:italic>\n                    transcription, thereby sustaining efficient intestinal lipid absorption. Pharmacological inhibition of menin with MI-463 recapitulated the metabolic effects of inducible\n                    <jats:italic>Men1<\/jats:italic>\n                    deletion. In a human gut organoid-on-chip system, MI-463 dose-dependently increased CES1 expression and markedly reduced lipid accumulation. Collectively, our findings identify menin as a regulator of intestinal lipid metabolism and suggest menin inhibition as a potential therapeutic strategy for obesity-related metabolic disorders.\n                  <\/jats:p>","DOI":"10.1172\/jci202709","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:00:27Z","timestamp":1786464027000},"source":"Crossref","is-referenced-by-count":0,"title":["Inhibiting menin attenuates high-fat diet\u2013induced weight gain by limiting intestinal lipid absorption in mice"],"prefix":"10.1172","volume":"136","author":[{"given":"Xiaoru","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."},{"name":"Central Laboratory, Yulin Hospital, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Yulin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyue","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, First Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenghao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghao","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoshun","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dabin","family":"Liu","sequence":"additional","affiliation":[{"name":"NHC Key Laboratory of Molecular Probes and Targeted Diagnosis and Therapy, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Geng","sequence":"additional","affiliation":[{"name":"Science and Technology Research Center, Harbin Medical University Cancer Hospital, Harbin, China."},{"name":"Key Laboratory of Molecular Oncology of Heilongjiang Province, Harbin, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Pancreatobiliary Surgery, The Second Affiliated Hospital of Harbin Medical University and Department of Immunology, School of Basic Medical Sciences, Harbin Medical University, Harbin, 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