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Proteomics data of hepatocytes in metabolism dysfunction associated steatohepatitis.

ABSTRACT: In this study, metabolism dysfunction associated steatohepatitis (MASH) hepatocytes and normal hepatocytes were collected from three MASH mouse models and normal diet control fixed-frozen liver sections with laser capture microdissection (LCM), respectively. Protein was processed from these LCM samples using the HDMSP method. LC-MS/MS analysis was performed with Orbitrap Astral mass spectrometer coupled with Vanquish Neo UHPLC system.

ORGANISM(S): Mus Musculus

SUBMITTER: Yan Wang

PROVIDER: PXD067929 | iProX | Mon Sep 01 00:00:00 BST 2025

REPOSITORIES: iProX

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Project description:The mechanisms underlying the progression of non-alcoholic steatohepatitis (NASH) are not completely elucidated. In this study we have integrated gene expression profiling of liver biopsies of NASH patients with translational studies in a mouse model of steatohepatitis and with pharmacological interventions in isolated hepatocytes to identify a novel mechanism implicated in the pathogenesis of NASH. By using high-density oligonucleotide microarray analysis we identified a significant enrichment of known genes involved in the multi-step catalysis of long chain polyunsaturated fatty acids, including delta-5 and 6 desaturases. A combined inhibitor of delta-5 and delta-6 desaturases significantly reduced intracellular lipid accumulation and inflammatory gene expression in isolated hepatocytes. Gas chromatography analysis revealed impaired delta-5 desaturase activity toward the omega-3 pathway in livers from mice with high-fat diet (HFD)-induced NASH. Consistently, restoration of omega-3 index in transgenic fat-1 mice expressing an omega-3 desaturase, which allows the endogenous conversion of omega-6 into omega-3 fatty acids, produced a significant reduction in hepatic insulin resistance, hepatic steatosis, macrophage infiltration and necroinflammatory liver injury, accompanied by attenuated expression of genes involved in inflammation, fatty acid uptake and lipogenesis. These results were comparable to those obtained in a group of mice receiving a HFD supplemented with EPA/DHA. Of interest, hepatocytes from fat-1 mice or supplemented with EPA exhibited synergistic anti-steatotic and anti-inflammatory actions with the delta-5/ delta-6 inhibitor. Conclusion: These findings indicate that both endogenous and exogenous restoration of the hepatic balance between omega-6 and omega-3 fatty acids and/or modulation of desaturase activities exert preventive actions in NASH. The complete database comprised the expression measurements of 18185 genes for liver sample groups: 8 non-alcoholic steatohepatitis (NASH ) and 7 control samples. This dataset is part of the TransQST collection.

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Proteomics data of hepatocytes in metabolism dysfunction associated steatohepatitis.

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