{"entity": "publication", "iuid": "bcb99b52a75a4ef4be7938b5dc910989", "timestamp": "2026-10-01T11:57:41.170Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/bcb99b52a75a4ef4be7938b5dc910989.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/bcb99b52a75a4ef4be7938b5dc910989"}}, "title": "Gut microbiota mediates SREBP-1c-driven hepatic lipogenesis and steatosis in response to zero-fat high-sucrose diet.", "authors": [{"family": "Bergentall", "given": "Mattias", "initials": "M"}, {"family": "Tremaroli", "given": "Valentina", "initials": "V"}, {"family": "Sun", "given": "Chuqing", "initials": "C"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Khan", "given": "Muhammad Tanweer", "initials": "MT"}, {"family": "Manner\u00e5s Holm", "given": "Louise", "initials": "L"}, {"family": "Olsson", "given": "Lisa", "initials": "L"}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO"}, {"family": "Molinaro", "given": "Antonio", "initials": "A"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Caesar", "given": "Robert", "initials": "R"}, {"family": "Nieuwdorp", "given": "Max", "initials": "M"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Mol Metab", "issn": "2212-8778", "volume": "97", "pages": "102162", "issn-l": "2212-8778"}, "abstract": "Sucrose-rich diets promote hepatic de novo lipogenesis (DNL) and steatosis through interactions with the gut microbiota. However, the role of sugar-microbiota dynamics in the absence of dietary fat remains unclear. This study aimed to investigate the effects of a high-sucrose, zero-fat diet (ZFD) on hepatic steatosis and host metabolism in conventionally raised (CONVR) and germ-free (GF) mice.\n\nCONVR and GF mice were fed a ZFD, and hepatic lipid accumulation, gene expression, and metabolite levels were analyzed. DNL activity was assessed by measuring malonyl-CoA levels, expression of key DNL enzymes, and activation of the transcription factor SREBP-1c. Metabolomic analyses of portal vein plasma identified microbiota-derived metabolites linked to hepatic steatosis. To further examine the role of SREBP-1c, its hepatic expression was knocked down using antisense oligonucleotides in CONVR ZFD-fed mice.\n\nThe gut microbiota was essential for sucrose-induced DNL and hepatic steatosis. In CONVR ZFD-fed mice, hepatic fat accumulation increased alongside elevated expression of genes encoding DNL enzymes, higher malonyl-CoA levels, and upregulation of SREBP-1c. Regardless of microbiota status, ZFD induced fatty acid elongase and desaturase gene expression and increased hepatic monounsaturated fatty acids. Metabolomic analyses identified microbiota-derived metabolites associated with hepatic steatosis. SREBP-1c knockdown in CONVR ZFD-fed mice reduced hepatic steatosis and suppressed fatty acid synthase expression.\n\nSucrose-microbiota interactions and SREBP-1c are required for DNL and hepatic steatosis in the absence of dietary fat. These findings provide new insights into the complex interplay between diet, gut microbiota, and metabolic regulation.", "doi": "10.1016/j.molmet.2025.102162", "pmid": "40345386", "labels": {"Adil Mardinoglu": "", "SciLifeLab Fellow": ""}, "xrefs": [{"db": "pmc", "key": "PMC12145984"}, {"db": "pii", "key": "S2212-8778(25)00069-9"}], "notes": [], "created": "2026-10-01T08:26:43.515Z", "modified": "2026-10-01T08:26:43.539Z"}