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Updated: May 10, 2025
Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
Published on: March 11, 2017
A host enzyme reduces metabolic dysfunction-associated steatotic liver disease (MASLD) by inactivating intestinal
Zhiyan Wang1, Nore Ojogun2, Yiling Liu1
1Department of Immunology, School of Basic Medical Sciences, Department of Trauma-Emergency & Critical Care Medicine, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.
Abstract:
The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has been increasing worldwide. Since gut-derived bacterial lipopolysaccharides (LPS) can travel via the portal vein to the liver and play an important role in producing hepatic pathology, it seemed possible that (1) LPS stimulates hepatic cells to accumulate lipid, and (2) inactivating LPS can be preventive. Acyloxyacyl hydrolase (AOAH), the eukaryotic lipase that inactivates LPS and oxidized phospholipids, is produced in the intestine, liver, and other organs. We fed mice either normal chow or a high-fat diet for 28 weeks and found that Aoah mice accumulated more hepatic lipid than did Aoah mice. In young mice, before increased hepatic fat accumulation was observed, Aoah mouse livers increased their abundance of sterol regulatory element-binding protein 1, and the expression of its target genes that promote fatty acid synthesis. Aoah mice also increased hepatic expression of Cd36 and Fabp3, which mediate fatty acid uptake, and decreased expression of fatty acid-oxidation-related genes Acot2 and Ppara. Our results provide evidence that increasing AOAH abundance in the gut, bloodstream, and/or liver may be an effective strategy for preventing or treating MASLD.
Insights
Mice lacking acyloxyacyl hydrolase (AOAH) accumulated more liver fat, indicating AOAH deficiency worsens metabolic dysfunction-associated steatotic liver disease (MASLD). Increasing AOAH may prevent or treat this condition.
Area of Science:
- Hepatology
- Metabolic Diseases
- Lipid Metabolism
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) incidence is rising globally.
- Gut-derived lipopolysaccharides (LPS) contribute to liver pathology.
- Acyloxyacyl hydrolase (AOAH) inactivates LPS and oxidized phospholipids.
Purpose of the Study:
- To investigate the role of AOAH in hepatic lipid accumulation.
- To determine if AOAH deficiency exacerbates MASLD.
- To explore AOAH as a potential therapeutic target for MASLD.
Main Methods:
- Mice were fed normal chow or a high-fat diet for 28 weeks.
- Hepatic lipid content was measured.
- Gene expression related to lipid metabolism was analyzed in wild-type and Aoah-deficient mice.
Main Results:
- Aoah-deficient mice accumulated significantly more hepatic lipid compared to controls.
- In young Aoah-deficient mice, increased sterol regulatory element-binding protein 1 and its target genes promoted fatty acid synthesis.
- Hepatic fatty acid uptake genes (Cd36, Fabp3) were upregulated, while fatty acid oxidation genes (Acot2, Ppara) were downregulated in Aoah-deficient mice.
Conclusions:
- AOAH deficiency promotes hepatic lipid accumulation and exacerbates MASLD.
- Modulating AOAH levels could be a novel strategy for preventing or treating MASLD.
- Targeting AOAH in the gut, bloodstream, or liver may offer therapeutic benefits for MASLD.
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