Comparative impact of dietary carbohydrates on the liver transcriptome in two strains of mice

Abstract

Excessive long-term consumption of dietary carbohydrates, including glucose, sucrose, or fructose, has been shown to have significant impact on genome-wide gene expression, which likely results from changes in metabolic substrate flux. However, there has been no comprehensive study on the acute effects of individual sugars on the genome-wide gene expression that may reveal the genetic changes altering signaling pathways, subsequent metabolic processes, and ultimately physiological/pathological responses. Considering that gene expressions in response to acute carbohydrate ingestion might be different in nutrient sensitive and insensitive mammals, we conducted comparative studies of genome-wide gene expression by deep mRNA sequencing of the liver in nutrient sensitive C57BL/6J and nutrient insensitive BALB/cJ mice. Furthermore, to determine the temporal responses, we compared livers from mice in the fasted state and following ingestion of standard laboratory mouse chow supplemented with plain drinking water or water containing 20% glucose, sucrose, or fructose. Supplementation with these carbohydrates induced unique extents and temporal changes in gene expressions in a strain specific manner. Fructose and sucrose stimulated gene changes peaked at 3 h postprandial, whereas glucose effects peaked at 12 h and 6 h postprandial in C57BL/6J and BABL/cJ mice, respectively. Network analyses revealed that fructose changed genes were primarily involved in lipid metabolism and were more complex in C57BL/6J than in BALB/cJ mice. These data demonstrate that there are qualitative and antitative differences in the normal physiological responses of the liver between these two strains of mice and C57BL/6J is more sensitive to sugar intake than BALB/cJ.