Chronic ingestion of a Western diet increases O-linked-尾-N-acetylglucosamine (O-GlcNAc) protein modification in the rat heart

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• 作者：H.M. Medford^a ; ^b ; J.C. Chatham^c ; S.A. Marsh^a ; ^{samarsh@wsu.edu}
• 关键词：Western diet ; saturated fat ; O-GlcNAc ; cardiac metabolism
• 刊名：Life Sciences
• 出版年：2012
• 期刊代码：62_00243205
• 类别：imm
• 出版时间：14 June, 2012
• 卷：90
• 期：23-24
• 页码：883-888
• 文件大小：485 K

摘要

Aims

Protein O-GlcNAcylation is both a nutrient sensing and cellular stress response that mediates signal transduction in the heart. Chronically elevated O-GlcNAc has been associated with the development of cardiac dysfunction at both the cellular and organ levels in obesity, insulin resistance and diabetes. Development of these pathologies is often attributed to diets high in saturated fat and sugar (a 鈥淲estern鈥?diet; WES) but a role for O-GlcNAc in diet-induced cardiac dysfunction has not been established. The aims of this study were to examine the effect of chronic consumption of WES on cardiac O-GlcNAcylation and investigate associations of O-GlcNAc with cardiac function and markers of cellular stress.

Main methods

Young male rats received either a control diet (CON; n = 9) or WES (n = 8) diet for 52 weeks.

Key findings

There was no evidence of cardiac dysfunction, advanced glycation endproduct (AGE) accumulation, pathological cardiac hypertrophy, calcium handling impairment, fibrosis or endoplasmic reticulum stress in WES hearts. However, cardiac O-GlcNAc protein, particularly in the higher molecular weight range, was significantly higher in WES hearts compared to CON (P < 0.05). Protein levels of the enzymes that regulate O-GlcNAc attachment were not different between groups; thus, the increased O-GlcNAcylation in WES hearts appears to be due to increased nutrient availability rather than enzymatic regulation of cellular stress.

Significance

These data suggest that diets high in saturated fat and sugar may contribute to the adverse effects of metabolic syndrome and diabetes by an O-GlcNAc-mediated process and that this may occur in the absence of overt cellular stress.