Tissue Specific Effects of Dietary Carbohydrates and Obesity on ChREBP alpha and ChREBP beta Expression

卷:51

Stamatikos, Alexis D. ; da Silva, Robin P. ; Lewis, Jamie T. ; Douglas, Donna N. ; Kneteman, Norman M. ; Jacobs, Rene L. ; Paton, Chad M.

Univ Georgia

关键词: De novo lipogenesis;    Fasting-refeeding;    Fatty liver;    Fructose;    Gluconeogenesis;    Obesity;   

DOI  :  10.1007/s11745-015-4090-0

学科分类：食品科学和技术

【 摘 要 】

Carbohydrate response element binding protein (ChREBP) regulates insulin-independent de novo lipogenesis. Recently, a novel ChREBP beta isoform was identified. The purpose of the current study was to define the effect of dietary carbohydrates (CHO) and obesity on the transcriptional activity of ChREBP isoforms and their respective target genes. Mice were subjected to fasting-refeeding of high-CHO diets. In all three CHO-refeeding groups, mice failed to induce ChREBP alpha, yet ChREBP beta increased 10- to 20-fold. High-fat fed mice increased hepatic ChREBP beta mRNA expression compared to chow-fed along with increased protein expression. To better assess the independent effect of fructose on ChREBP alpha/beta activity, HepG2 cells were treated with fructose +/- A a fructose-1,6-bisphosphatase inhibitor to suppress gluconeogenesis. Fructose treatment in the absence of gluconeogenesis resulted in increased ChREBP activity. To confirm the existence of ChREBP beta in human tissue, primary hepatocytes were incubated with high-glucose and the expression of ChREBP alpha and -beta was determined. As with the animal models, glucose induced ChREBP beta expression while ChREBP alpha was decreased. Taken together, ChREBP beta is more responsive to changes in dietary CHO availability than the -alpha isoform. Diet-induced obesity increases basal expression of ChREBP beta, which may increase the risk of developing hepatic steatosis, and fructose-induced activation is independent of gluconeogenesis.