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dc.contributor.authorPant, R.-
dc.contributor.authorKabeer, S.W.-
dc.contributor.authorSharma, S.-
dc.contributor.authorKumar, V.-
dc.contributor.authorPatra, D.-
dc.contributor.authorPal, D.-
dc.contributor.authorTikoo, K.-
dc.date.accessioned2024-10-13T13:19:57Z-
dc.date.available2024-10-13T13:19:57Z-
dc.date.issued2024-10-13-
dc.identifier.urihttp://dspace.iitrpr.ac.in:8080/xmlui/handle/123456789/4729-
dc.description.abstractNonalcoholic fatty liver disease (NAFLD) is associated with an increased ratio of classically activated M1 macrophages/Kupffer cells to alternatively activated M2 macrophages, which plays an imperative role in the development and progression of NAFLD. However, little is known about the precise mechanism behind macrophage polarization shift. Here, we provide evidence regarding the relationship between the polarization shift in Kupffer cells and autophagy resulting from lipid exposure. High-fat and high-fructose diet supplementation for 10 weeks significantly increased the abundance of Kupffer cells with an M1-predominant phenotype in mice. Interestingly, at the molecular level, we also observed a concomitant increase in expression of DNA methyltransferases DNMT1 and reduced autophagy in the NAFLD mice. We also observed hypermethylation at the promotor regions of autophagy genes (LC3B, ATG-5, and ATG-7). Furthermore, the pharmacological inhibition of DNMT1 by using DNA hypomethylating agents (azacitidine and zebularine) restored Kupffer cell autophagy, M1/M2 polarization, and therefore prevented the progression of NAFLD. We report the presence of a link between epigenetic regulation of autophagy gene and macrophage polarization switch. We provide the evidence that epigenetic modulators restore the lipid-induced imbalance in macrophage polarization, therefore preventing the development and progression of NAFLD.en_US
dc.language.isoen_USen_US
dc.subjectmacrophage polarizationen_US
dc.subjectautophagyen_US
dc.subjectDNA hypomethylating agentsen_US
dc.subjectepigenetic reprogrammingen_US
dc.subjectNAFLDen_US
dc.titlePharmacological inhibition of DNMT1 restores macrophage autophagy and M2 polarization in Western diet–induced nonalcoholic fatty liver diseaseen_US
dc.typeArticleen_US
Appears in Collections:Year-2023

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