{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:33:09Z","timestamp":1791581589579,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"46","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32071153"],"award-info":[{"award-number":["32071153"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Glycerol kinase (GK) participates in triglyceride (TG) synthesis by catalyzing glycerol metabolism. Whether GK contributes to nonalcoholic fatty liver (NAFL) is unclear. The expression of hepatic Gk is found to be increased in diet\u2010induced and genetic mouse models of NAFL and is positively associated with hepatic SREBP\u20101c expression and TG levels. Cholesterol and fatty acids stimulate GK expression in hepatocytes. In HFD\u2010induced NAFL mice, knockdown of hepatic Gk decreases expression of SREBP\u20101c and its target lipogenic genes as well as DGAT1\/2, increases serum glycerol levels, decreases serum TG levels, and attenuates hepatic TG accumulation. Overexpression of GK in hepatocytes in mice or in culture produces opposite results. Mechanistic studies reveal that GK stimulates SREBP\u20101c transcription directly by binding to its gene promoter and indirectly by binding to SREBP\u20101c protein, thereby increasing lipogenic gene expression and de novo lipogenesis. Studies with truncated GK and mutant GKs indicate that GK induces SREBP\u20101c transcription independently of its enzyme activity. GK contributes to lipid homeostasis under physiological conditions by catalyzing glycerol metabolism rather than by regulating SREBP\u20101c transcription. Collectively, these results demonstrate that increased hepatic GK promotes de novo lipogenesis and TG synthesis in NAFL by stimulating SREBP\u20101c transcription and DGAT1\/2 expression and catalyzing glycerol metabolism.<\/jats:p>","DOI":"10.1002\/advs.202401311","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T12:41:10Z","timestamp":1729168870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Glycerol Kinase Drives Hepatic de novo Lipogenesis and Triglyceride Synthesis in Nonalcoholic Fatty Liver by Activating\n                    <i>SREBP\u20101c<\/i>\n                    Transcription, Upregulating DGAT1\/2 Expression, and Promoting Glycerol Metabolism"],"prefix":"10.1002","volume":"11","author":[{"given":"Shuyu","family":"Ouyang","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition Metabolism and Food Safety Shanghai Institute of Nutrition and 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