Regulation of gene expression during the fasting-feeding cycle of the liver displays mouse strain specificity.

ABSTRACT

The liver maintains metabolic homeostasis by integrating the regulation of nutrient status with both hormonal and neural signals. Many studies on hepatic signaling in response to nutrients have been conducted in mice. However, no in-depth study is currently available that has investigated genome-wide changes in gene expression during the normal physiological fasting-feeding cycle in nutrient-sensitive and -insensitive mice. Using two strains of mice, C57BL/6J and BALB/cJ, and deploying deep RNA-Seq complemented with quantitative RT-PCR, we found that feeding causes substantial and transient changes in gene expression in the livers of both mouse strains. The majority of significantly changed transcripts fell within the areas of biological regulation and cellular and metabolic processes. Among the metabolisms of three major types of macronutrients (i.e. carbohydrates, proteins, and lipids), feeding affected lipid metabolism the most. We also noted that the C57BL/6J and BALB/cJ mice significantly differed in gene expression and in changes in gene expression in response to feeding. In both fasted and fed states, both mouse strains shared common expression patterns for about 10,200 genes, and an additional 400-600 genes were differentially regulated in one strain but not the other. Among the shared genes, more lipogenic genes were induced upon feeding in BABL/cJ than in C57BL/6J mice. In contrast, in the population of differentially enriched genes, C57BL/6J mice expressed more genes involved in lipid metabolism than BALB/cJ mice. In summary, these results reveal that the two mouse strains used here exhibit several differences in feeding-induced hepatic responses in gene expression, especially in lipogenic genes.