Selective transcriptomic dysregulation of metabolic pathways in liver and retina by short- and long-term dietary hyperglycemia
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
Affiliations
Anupam K. Mondal
Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, USA
Daniel C. Brock
Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, USA
Sheldon Rowan
Laboratory for Nutrition & Vision Research, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, and Department of Molecular and Chemical Biology, Tufts University, Boston, MA, USA; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA
Zhi-Hong Yang
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA
Krishna Vamsi Rojulpote
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA
Kelsey M. Smith
Laboratory for Nutrition & Vision Research, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, and Department of Molecular and Chemical Biology, Tufts University, Boston, MA, USA
Sarah G. Francisco
Laboratory for Nutrition & Vision Research, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
Eloy Bejarano
Laboratory for Nutrition & Vision Research, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; School of Health Sciences and Veterinary School, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain
Milton A. English
Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, USA
Amy Deik
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Sarah Jeanfavre
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Clary B. Clish
Broad Institute of MIT and Harvard, Cambridge, MA, USA
Alan T. Remaley
Lipoprotein Metabolism Section, Translational Vascular Medicine Branch, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA
Allen Taylor
Laboratory for Nutrition & Vision Research, JM-USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; Friedman School of Nutrition Science and Policy, and Department of Molecular and Chemical Biology, Tufts University, Boston, MA, USA; Department of Ophthalmology, Tufts University School of Medicine, Boston, MA, USA; Corresponding author
Anand Swaroop
Neurobiology Neurodegeneration & Repair Laboratory, National Eye Institute (NEI), National Institutes of Health (NIH), Bethesda, MD, USA; Corresponding author
Summary: 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.
