Causative and Sanative dynamicity of ChREBP in Hepato-Metabolic disorders

Eur J Cell Biol. 2020 Nov;99(8):151128. doi: 10.1016/j.ejcb.2020.151128. Epub 2020 Nov 2.

Abstract

ChREBP is the master regulator of carbohydrate dependent glycolytic and lipogenic flux within metabolic tissues. It plays a vital role in hyper-calorific milieu by activating glycolysis, lipogenesis along with pentose phosphate shunt and glycogen synthesis, fostering immediate reduction in the systemic glycemic levels. Liver being the primary organ to sense disproportionate dietary intake and linked physiological stress, stimulates ChREBP to perform the aforementioned processes. Activated ChREBP also inhibits lipolysis and encourages proper disposal of excessive triglycerides into adipocytes from the liver ablating hepatic intracellular lipid trafficking. Chronic overeating or onset of positive energy balance, hyper-activates ChREBP and signals development, intensification of hepato-metabolic disorders, and allied discrepancies in the whole-body metabolic functioning. ChREBP thus gets negatively connotated as the primary regulator of hepatic disorders, owing to its inherent features as the primary glycemic sensor and the only transcription factor that can transduce glucose-dependent glycolytic and lipogenic signals. Through this review, we - try to recapitulate and emphasize on the sanative events coordinated by ChREBP in several pathophysiological states. In totality, we aim to uncouple the disease-causing aspects of ChREBP from its positive attributes evoked during a metabolic crisis, in hepato-metabolic diseases.

Keywords: ChREBP; GSD-1; Glucose; L-PK; NAFLD; PAHSA; SCD1.

Publication types

  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
  • Humans
  • Liver / pathology*
  • Liver Diseases / genetics*
  • Male
  • Metabolic Diseases / genetics*
  • Mice
  • Non-alcoholic Fatty Liver Disease / genetics*
  • Non-alcoholic Fatty Liver Disease / pathology
  • Nuclear Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • MLXIPL protein, human
  • Nuclear Proteins