Effects of High Sugar Consumption on Transcriptome of Adipose Tissues and Metabolome of Blood in Mice

Abstract

It is well known that sustained sugar consumption leads to the increase in prevalence of metabolic syndrome. Previously, animal model experiments were conducted for demonstrating the effects of sugar intake on metabolic syndrome-related markers in two different levels of dietary fat. Mice fed sugar solution with normal fat diet were compared with those fed plain water with normal fat diet, plain water with high fat, or sugar solution with high fat diet. Surprisingly, heightened level of serum triglyceride (TG) was found only in normal fat with sugar treated group, not in high fat and high fat with sugar fed groups, compared to control group. Another observation that there was dramatic increase in lipid accumulation in adipose tissue of high fat treated groups, but no increase in normal fat with sugar treated group, led us to hypothesize there might be an impairment in TG clearance from blood to adipocytes in this model. Therefore, it was aimed to investigate the changes in transcriptional networks in adipose tissues of normal fat and sugar treated group compared to those of control, high fat and high fat with sugar treated groups. Firstly, RNA sequencing was performed in epididymal adipose tissues of three individual mice in each group. 6,849 differentially expressed genes in one group from the others were identified by ANOVA test. Functional enrichment analysis of the significant genes demonstrated that sugar ingestion with normal fat diet upregulated expression of genes involved in energy metabolism, especially in mitochondrial function. Moreover, the changes in mitochondrial functions affected the expression of transcription factor CREB and downstream molecules implicated in TG accumulation. The transcripts expression of CREB downstream molecules were reduced in normal fat diet and sugar drink treated mice, and this showed us the possibilities that the size of adipocytes did not expand in normal fat diet and sugar treated mice due to decrease of genes involved in TG accumulation in adipocytes. Also the expressions of fatty acid transporters were reduced by normal fat diet and sugar consumption, and this was accompanied by elevation of the level of fatty acids as well as TG in serum lipid metabolomics profile derived by LC-MS analysis. The concentration of majority of TG species in serum lipid profiles was increased by normal fat and sugar drink intake, whereas the concentration of TG species which were including double bond more than six was not elevated. These findings demonstrate the mechanism by which high sugar diet develop impairment of serum TG clearance into adipose tissues and provide new candidate for markers to target for hypertriglyceridemia prevention.