Hepatic transcriptional responses to fasting and feeding

Mammals undergo regular cycles of fasting and feeding that engage dynamic transcriptional responses in metabolic tissues. Here we review advances in our understanding of the gene regulatory networks that contribute to hepatic responses to fasting and feeding. The advent of sequencing and -omics techniques have begun to facilitate a holistic understanding of the transcriptional landscape and its plasticity. We highlight transcription factors, their cofactors, and the pathways that they impact. We also discuss physiological factors that impinge on these responses, including circadian rhythms and sex differences. Finally, we review how dietary modifications modulate hepatic gene expression programs. In mammals, the transitions between fasting and fed states are accompanied by complex changes in hepatic gene expression. The liver is a central hub for coordination of fasting-feeding transitions given its roles in maintaining blood glucose levels, processing dietary nutrients, and regulating whole-body energy metabolism (for review, see Trefts et al. 2017). During fasting the liver is the target of hormones such as glucagon, which shift it into an energy production mode (Sutherland and Cori 1951). In response, the liver takes up free fatty acids (FFAs) released into the circulation by adipose lipolysis to provide energy for itself and to generate ketones for use by other tissues (Fine and Williams 1960). It also breaks down glycogen and amino acids to generate glucose for the brain (for review, see Berg et al. 2002). In the postprandial state, signaled by insulin and the influx of di