The Short-Term Effect of a High-Glycemic Diet on Mouse Obesity and Intestinal Microbiota Composition

Abstract

Objectives High glycemic index diet has been demonstrated to induce obesity and insulin resistance. The role of gut microbiota, as a key mediator of several metabolic syndromes, has not been elucidated. The objective of this project is to understand the effect of gut microbiota in a high-glycemic diet-induced obesity and associated metabolic complications. Methods Male C57Bl6/J mice aged 8–9 weeks were fed with a high-glycemic diet (HG, amylopectin-based) or low-glycemic diet (LG, amylose-based) ad libitum for 8 weeks. Body composition was determined by MRIs. Intraperitoneal glucose tolerance tests were performed after 6 weeks on diet. Mice were euthanized after 8 weeks on diet. Results After two weeks on diet, the HG group (n = 12) mice had a significantly higher body fat mass by MRI analysis, as compared to the LG group (n = 12) despite having similar body weight and equal food consumption. After 6 weeks, mice in the HG group had a significantly higher fasting glucose level compared to the LG group. There was no difference in fasting triglyceride level. Gonadal, subcutaneous and brown fat adipose tissue weight were significantly higher in the HG group after 8 weeks on diet. 16S rDNA sequencing on feces showed that the HG mice have a significantly higher Shannon diversity and different overall microbiome structure compared to the LG mice. The microbial community in the LG group was predominated by Bacteroidetes, particularly by Bacteroides thetaiotaomicron (Relative abundance 48.65 ± 12.88% versus HG 14.69 ± 0.07%), while the HG group was predominated by Firmicutes. Ongoing analysis will investigate the relative role of key microbial taxa on obesity and glucose homeostasis. Conclusions Consuming two weeks of a high-glycemic index diet induced adiposity and hyperglycemia along with a shift of the overall gut microbiota composition compared to a low-glycemic index diet. Funding Sources NIH, USDA, Robert C and Veronica Atkins Foundation

High Glycemia and Soluble Epoxide Hydrolase in Females: Differential Multiomics in Murine Brain Microvasculature

“…In this present study, we characterized for the first time the effect of a HGD on female mice brain hippocampal microvessels using large-scale transcriptomics. In our experimental mice, we did not observe any statistically significant differences in the body weight, total cholesterol, glucose, or insulin levels in the HGD compared to the LGD at the end of dietary feeding, consistent with previously published studies for these experimental models [ 43 , 45 , 54 , 55 , 56 , 57 ]. Our current study shows for the first time that the HGD had opposite gene expression patterns compared to the LGD, characterized by mostly downregulation of differentially expressed protein coding and non-protein coding genes including miRNAs, snoRNAs and lncRNAs.…”

Inhibition of Soluble Epoxide Hydrolase Is Protective against the Multiomic Effects of a High Glycemic Diet on Brain Microvascular Inflammation and Cognitive Dysfunction

“…We used a relevant model of glycemic index and demonstrated the expected significant differences in weight, cholesterol, glucose, and insulin levels consistent with what has been published previously for these experimental models [19,[63][64][65]. To our knowledge, the present study shows for the first time that the HGD has distinct differential effects on gene expression that are different from the LGD and characterized by up-regulation of differentially expressed protein-coding genes, transcription factors, as well as non-protein-coding genes (miRNAs, snoRNAs, and lncRNAs), that are involved in five major cellular pathways: neurodegenerative diseases (Alzheimer's disease), endothelial cell function (focal adhesion), cell signaling (PPAR signaling, PI3K-Akt signal- An additional finding of the two-factor analysis was that when the individual DEGs of the relevant pathways shown in Figure 10A (77 DEGs) were examined, it again became apparent that the sEHI reverted the gene expression profile of brain hippocampal microvascular endothelium of mice on the HGD to a profile similar to that of the LGD.…”