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Diet‑inducing hypercholesterolemia show decreased O‑GlcNAcylation of liver proteins through modulation of AMPK.

Sanjana, Jagannath and Smitha, H. M. and Nandini, C. D. (2023) Diet‑inducing hypercholesterolemia show decreased O‑GlcNAcylation of liver proteins through modulation of AMPK. Journal of Physiology and Biochemistry.

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Abstract

O-GlcNAcylation, a nutritionally driven, post-translational modification of proteins, is gaining importance because of its health implications. Changes in O-GlcNAcylation are observed in various disease conditions. Changes in O-GlcNAcylation by diet that causes hypercholesterolemia are not critically looked into in the liver. To address it, both in vitro and in vivo approaches were employed. Hypercholesterolemia was induced individually by feeding cholesterol (H)/high-fat (HF) diet. Global O-GlcNAcylation levels and modulation of AMPK activation in both preventive and curative approaches were looked into. Diet-induced hypercholesterolemia resulted in decreased O-GlcNAcylation of liver proteins which was associated with decreased O-linked N-acetylglucosaminyltransferase (OGT) and Glutamine fructose-6-phosphate amidotransferase-1 (GFAT1). Activation of AMPK by metformin in preventive mode restored the O-GlcNAcylation levels; however, metformin treatment of HepG2 cells in curative mode restored O-GlcNAcylation levels in HF but failed to in H condition (at 24 h). Further, maternal faulty diet resulted in decreased O-GlcNAcylation in pup liver despite feeding normal diet till adulthood. A faulty diet modulates global O-GlcNAcylation of liver proteins which is accompanied by decreased AMPK activation which could exacerbate metabolic syndromes through fat accumulation in the liver.

Item Type: Article
Uncontrolled Keywords: Metabolic disease · Hypercholesterolemia · Hexosamine biosynthetic pathway · O-GlcNAcylation · AMPK
Subjects: 500 Natural Sciences and Mathematics > 07 Life Sciences > 03 Biochemistry & Molecular Biology > 13 Molecular Biochemistry
Divisions: Molecular Nutrition
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 09 Dec 2023 05:05
Last Modified: 09 Dec 2023 05:05
URI: http://ir.cftri.res.in/id/eprint/16864

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