Hepatic transcriptional responses to fasting and feeding

Abstract

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.

Global-run on sequencing identifies Gm11967 as an Akt-dependent long noncoding RNA involved in insulin sensitivity

“…Nutrient availability induces dramatic changes in liver through the action of insulin and other metabolites ( Bideyan et al., 2021 ). In order to obtain a global view of these changes, we used GRO-seq to measure nascent RNA transcription in overnight fasted and 2-h refed control mice.…”

Hormone-controlled cooperative binding of transcription factors drives synergistic induction of fasting-regulated genes

“…The manner by which extracellular signals are integrated and translated in cells to produce a coherent response is poorly understood. Here, we investigated the hepatic fasting response which is heavily reliant on transcriptional regulation ( 14 , 23 , 58 ). This response is controlled by the combinatorial effect of several signals, chief among them are glucagon and glucocorticoids.…”

“…While other TFs were shown to play a role in regulating gluconeogenic gene expression ( 14 , 23 ), CREB and GR were among a group of four TFs that were found to play a genome-wide role in the transcriptional response to fasting and were shown to preferentially bind hundreds of hepatic enhancers promoting the fasting response ( 3 ). Among these four TFs, only CREB and GR are potently stimulated by fasting hormones.…”

Dietary carbohydrates: Pathogenesis and potential therapeutic targets to obesity‐associated metabolic syndrome

“…There is strong evidence suggesting that high-calorie diets downregulate liver nuclear receptors such as SIRT1, which are implicated in abnormal glucose, lipid, and xenobiotic metabolism, DNA damage, mitochondrial dysfunction, and immune system alteration. 147,148 Strikingly, during early calorie restriction, hepatic SIRT1 is upregulated, which enhances metabolism (glucose, protein, fatty acids, and cholesterol) through the activation of fibroblast growth factor 21 (FGF21) (Figure 2). [148][149][150] FGF21 is a hepatokine that recently got substantial priorities for promising therapeutic targets of MetS.…”

“…147,148 Strikingly, during early calorie restriction, hepatic SIRT1 is upregulated, which enhances metabolism (glucose, protein, fatty acids, and cholesterol) through the activation of fibroblast growth factor 21 (FGF21) (Figure 2). [148][149][150] FGF21 is a hepatokine that recently got substantial priorities for promising therapeutic targets of MetS. 151 In obese Gottingen minipigs, treatment with FGF 21 reduced food intake (50%) and body weight (18 kg) after 14 weeks.…”