Jagannath Sanjana, Mallanna Smitha Honnalagere, Nandini C D
Department of Molecular Nutrition, CSIR-Central Food Technological Research Institute, Mysore, Karnataka, 570020, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
J Physiol Biochem. 2024 Feb;80(1):205-218. doi: 10.1007/s13105-023-00997-7. Epub 2023 Nov 24.
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.
O-连接的N-乙酰葡糖胺化（O-GlcNAcylation）是一种由营养驱动的蛋白质翻译后修饰，由于其对健康的影响而日益受到重视。在各种疾病状态下都观察到了O-GlcNAcylation的变化。饮食引起的高胆固醇血症导致的O-GlcNAcylation变化在肝脏中尚未得到深入研究。为了解决这个问题，我们采用了体外和体内两种方法。通过喂食胆固醇（H）/高脂肪（HF）饮食分别诱导高胆固醇血症。研究了在预防和治疗方法中整体O-GlcNAcylation水平以及AMPK激活的调节情况。饮食诱导的高胆固醇血症导致肝脏蛋白质的O-GlcNAcylation减少，这与O-连接的N-乙酰葡糖胺基转移酶（OGT）和谷氨酰胺果糖-6-磷酸酰胺转移酶-1（GFAT1）的减少有关。二甲双胍在预防模式下激活AMPK可恢复O-GlcNAcylation水平；然而，二甲双胍在治疗模式下处理HepG2细胞可恢复HF条件下的O-GlcNAcylation水平，但在H条件下（24小时）未能恢复。此外，尽管幼崽成年前喂食正常饮食，但母体的不良饮食导致幼崽肝脏中的O-GlcNAcylation减少。不良饮食会调节肝脏蛋白质的整体O-GlcNAcylation，同时伴随着AMPK激活的减少，这可能通过肝脏脂肪堆积加剧代谢综合征。
