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Multi-omics study identifies unique metabolic responses to high glycemic diet in liver and retina

ABSTRACT: High glycemic index (HGI) diet induces hyperglycemia, an etiologic risk factor in major diseases affecting multiple organ systems. We hypothesized that adaptation to dietary glycemic exposure is tissue-specific and depends on the length of intake. We therefore evaluated transcriptomic responses to HGI diet after one or 12-months in the liver and retina of C57BL/6J wild-type mice. In the liver, the genes associated with inflammation and fatty acid metabolism were altered within one-month of HGI diet, whereas 12-month HGI diet-fed group showed dysregulated expression of multiple cytochrome P450 genes and overexpression of key lipogenic factors including Srebf1 and Elovl5. In contrast, retinal transcriptomes exhibited fewer HGI-related changes after one-month, and notable alterations in energy metabolism genes were apparent after 12-months of HGI diet. Fatty acid profiles of liver samples corroborated transcriptomic trends and revealed elevated levels of monounsaturated fatty acid in the HGI group. Conversely, saturated fatty acids and polyunsaturated fatty acids were lower in livers of HGI fed animals, regardless of length of exposure. HGI also resulted in a significant increase in blood low-density lipoprotein (LDL) and overall cholesterol levels. We also uncovered diet-aging interactions affecting expression of mitochondrial oxidative phosphorylation genes in the liver, and inherited disease-associated genes in the retina. Our findings provide new insights into tissue-specific adaptive mechanisms, focusing on the liver and the retina, to dietary hyperglycemia.

ORGANISM(S): Mus musculus

PROVIDER: GSE243843 | GEO | 2024/02/05

REPOSITORIES: GEO

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Project description:We previously reported that a low versus high glycemic index (GI) diet on a high fat (30% kcal fat) background (LGI and HGI, respectively) significantly retarded adverse health effects in C57BL/6J male mice. The LGI diet enhanced whole body insulin sensitivity and repressed high fat diet-induced body and adipose tissue weight gain, resulting in reduced serum leptin and resistin levels (Faseb J 2009; 23: 1092-1101). How white adipose tissue (WAT) is effected is examined in the present study. We characterized the molecular mechanisms underlying the GI-mediated effects in WAT using whole genome transcriptomics technology. We show that a LGI vs. HGI diet mainly exerts its beneficial effects on substrate metabolism, especially insulin signaling of fatty acid metabolism. In addition, cell adhesion and cytoskeleton remodeling showed reduced expression in line with lower WAT mass, but it might also be due to altered insulin sensitivity. An important transcription factor showing enhanced expression is PPARgamma. Furthermore, serum levels of triglycerides, total cholesterol, HDL- and LDL-cholesterol were significantly reduced by a LGI vs. HGI diet, and muscle insulin sensitivity was significantly increased as analyzed by PKB/Akt phosphorylation. Cumulatively, even though these mice were fed a high fat diet, the low versus high GI induced significantly favorable changes in metabolism in WAT. These effects suggest a partial overlap with pharmacological approaches by thiazolidinediones (TZDs) to treat insulin resistance and statins and plantsterols/stanols for hypercholesterolemia. It is therefore tempting to speculate that such a dietary approach might beneficially support pharmacological treatment of insulin resistance or hypercholesterolemia in humans. We analyzed 19 epididymal whie adipose tissue (epiWAT) samples from a 13 week High fat diet, Low glycemic index dietary group (LGI, n=9) versus a High fat diet, High glycemic index dietary group (HGI, n=10) after 13 weeks of feeding wildtype C57BL/6J male adult mice. Of the 19 arrays, we excluded 2 arrays for downstream analysis based on quality control (total final set contains 8 LGI and 9 HGI samples).

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Multi-omics study identifies unique metabolic responses to high glycemic diet in liver and retina

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