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

• Published in: iScience Vol. 27; no. 2; p. 108979
• Main Authors: Mondal, Anupam K., Brock, Daniel C., Rowan, Sheldon, Yang, Zhi-Hong, Rojulpote, Krishna Vamsi, Smith, Kelsey M., Francisco, Sarah G., Bejarano, Eloy, English, Milton A., Deik, Amy, Jeanfavre, Sarah, Clish, Clary B., Remaley, Alan T., Taylor, Allen, Swaroop, Anand
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16-02-2024; Elsevier
• Subjects: Metabolomics; Physiology; Transcriptomics; Metabolomics; Transcriptomics; Physiology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108979

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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•High glycemic index diet has distinct impact on metabolic genes in the liver and retina•HGI diet raises hepatic levels of monounsaturated fatty acids and blood cholesterol•Blood levels of LDL-cholesterol significantly increase after long-term HGI diet•Diet-aging interaction distinctly alters gene expression in the liver and retina
Physiology; Metabolomics; Transcriptomics