Selective transcriptomic dysregulation of metabolic pathways in liver and retina by short- and long-term dietary hyperglycemia

短期和长期饮食性高血糖导致肝脏和视网膜代谢途径的选择性转录组失调

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作者:Anupam K Mondal, Daniel C Brock, Sheldon Rowan, Zhi-Hong Yang, Krishna Vamsi Rojulpote, Kelsey M Smith, Sarah G Francisco, Eloy Bejarano, Milton A English, Amy Deik, Sarah Jeanfavre, Clary B Clish, Alan T Remaley, Allen Taylor, Anand Swaroop

Abstract

A high glycemic index (HGI) diet induces hyperglycemia, a risk factor for diseases affecting multiple organ systems. Here, we evaluated tissue-specific adaptations in the liver and retina after feeding HGI diet to mice for 1 or 12 month. In the liver, genes associated with inflammation and fatty acid metabolism were altered within 1 month of HGI diet, whereas 12-month HGI diet-fed group showed dysregulated expression of cytochrome P450 genes and overexpression of lipogenic factors including Srebf1 and Elovl5. In contrast, retinal transcriptome exhibited HGI-related notable alterations in energy metabolism genes only after 12 months. Liver fatty acid profiles in HGI group revealed higher levels of monounsaturated and lower levels of saturated and polyunsaturated fatty acids. Additionally, HGI diet increased blood low-density lipoprotein, and diet-aging interactions affected expression of mitochondrial oxidative phosphorylation genes in the liver and disease-associated genes in retina. Thus, our findings provide new insights into retinal and hepatic adaptive mechanisms to dietary hyperglycemia.

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