{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T10:20:28Z","timestamp":1783938028235,"version":"3.55.0"},"reference-count":49,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,1]]},"abstract":"<jats:p>Dysregulation of hepatic VLDL secretion contributes to the pathogenesis of metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD) and hyperlipidemia. Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) had malfunctioning roles in the pathogenesis of NAFLD. However, the function of lncRNAs in controlling hepatic VLDL secretion remains largely unillustrated. Here, we identified a novel lncRNA, lncRNA regulator of hyperlipidemia (lncRHPL), which was liver-enriched, downregulated on high-fat diet feeding, and inhibited by oleic acid treatment in primary hepatocytes. With genetic manipulation in mice and primary hepatocytes, depletion of lncRHPL induces hepatic VLDL secretion accompanied by decreased hepatic lipid contents. Conversely, lncRHPL restoration reduces VLDL secretion with increased lipid deposition in hepatocytes. Mechanistic analyses indicate that lncRHPL binds directly to heterogeneous nuclear ribonuclear protein U (hnRNPU), and thereby enhances its stability, and that hnRNPU can transcriptional activate Bmal1, leading to inhibition of VLDL secretion in hepatocytes. lncRHPL deficiency accelerates the protein degradation of hnRNPU and suppresses the transcription of Bmal1, which in turn activates VLDL secretion in hepatocytes. With results taken together, we conclude that lncRHPL is a novel suppressor of hepatic VLDL secretion. Activating the lncRHPL\/hnRNPU\/BMAL1\/MTTP axis represents a potential strategy for the maintenance of intrahepatic and plasma lipid homeostasis.<\/jats:p>","DOI":"10.2337\/db21-1145","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T14:52:03Z","timestamp":1656600723000},"page":"1915-1928","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":25,"title":["Long Noncoding RNA lncRHPL Regulates Hepatic VLDL Secretion by Modulating hnRNPU\/BMAL1\/MTTP Axis"],"prefix":"10.2337","volume":"71","author":[{"given":"Xuan","family":"Shen","sequence":"first","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuetao","family":"Ji","sequence":"additional","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical 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Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Huang","sequence":"additional","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Qin","sequence":"additional","affiliation":[{"name":"2State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9309-3546","authenticated-orcid":false,"given":"Hongwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"3Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-1725","authenticated-orcid":false,"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"1The Key Laboratory of Rare Metabolic Disease, Department of Biochemistry and Molecular Biology, The Key Laboratory of Human Functional Genomics of Jiangsu Province, Key Laboratory of Targeted Intervention of Cardiovascular 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