A Host Enzyme Reduces Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) by Inactivating Intestinal Lipopolysaccharide

• DOI: 10.7554/elife.100731.2
• Publication Date: 2025-04-09T14:36:07Z
• Authors: Zhiyan Wang; Nore Ojogun; Yiling Liu; Lu Gan; Zeling Xiao; Jintao Feng; Wei Jiang; Yeying Chen; Benkun Zou; Cheng-Yun Yu; Changshun Li; Asha Ashuo; Xiaobo Li; Mingsheng Fu; Jian Wu; Yiwei Chu; Robert Munford; Mingfang Lu
• Keywords: Liver enzyme

The incidence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been increasing world-wide. Since gut-derived bacterial lipopolysaccharides (LPS) can travel via the portal vein to liver and play an important role in producing hepatic pathology, it seemed possible that (1) LPS stimulates cells accumulate lipid, (2) inactivating be preventive. Acyloxyacyl hydrolase (AOAH), eukaryotic lipase inactivates oxidized phospholipids, is produced intestine, liver, other organs. We fed mice either normal chow or a high-fat diet for 28 weeks found Aoah −/− accumulated more lipid than did +/+ mice. In young mice, before increased fat accumulation was observed, mouse livers their abundance Sterol Regulatory Element-Binding Protein 1 (SREBP1) expression its target genes promote fatty acid synthesis. also CD36 Fabp3, which mediate uptake, decreased oxidation-related Acot2 Ppar-α. Our results provide evidence AOAH gut, bloodstream and/or may effective strategy preventing treating MASLD.