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This study investigates the effects and molecular mechanisms of butyrate, a dietary fiber metabolite of gut microbiota, on lipid metabolism in hepatocytes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>This study examines the effects of butyrate (0\u20138\u00a0mM) on lipid metabolism in primary hepatocytes. The results show that butyrate (2\u00a0mM) consistently inhibits lipogenic genes and activates lipid oxidation\u2010related gene expression in hepatocytes. Furthermore, butyrate modulates lipid metabolism genes, reduces fat droplet accumulation, and activates the calcium\/calmodulin\u2010dependent protein kinase II (CaMKII)\/histone deacetylase 1 (HDAC1)\u2010cyclic adenosine monophosphate response element binding protein (CREB) signaling pathway in the primary hepatocytes and liver of wild\u2010type (WT) mice, but not in G\u2010protein\u2010coupled receptor 41 (GPR41) knockout and 43 (GPR43) knockout mice. This suggests that butyrate regulated hepatic lipid metabolism requires GPR41 and GPR43. Finally, the study finds that dietary butyrate supplementation (5%) ameliorates hepatic steatosis and abnormal lipid metabolism in the liver of mice fed a high\u2010fat and fiber\u2010deficient diet for 15 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This work reveals that butyrate improves hepatic lipid metabolism through the GPR41\/43\u2010CaMKII\/HDAC1\u2010CREB pathway, providing support for consideration of butyrate as a dietary supplement to prevent the progression of NAFLD induced by the Western\u2010style diet.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mnfr.202200597","type":"journal-article","created":{"date-parts":[[2022,11,16]],"date-time":"2022-11-16T04:26:01Z","timestamp":1668572761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Butyrate Attenuates Hepatic Steatosis Induced by a High\u2010Fat and Fiber\u2010Deficient Diet via the Hepatic GPR41\/43\u2010CaMKII\/HDAC1\u2010CREB Pathway"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9406-2437","authenticated-orcid":false,"given":"Mingxuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and Immunology Xuzhou Medical University  Xuzhou Jiangsu 221004 P. 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