Transcriptional regulation of hepatic lipogenesis

Nat Rev Mol Cell Biol. 2015 Nov;16(11):678-89. doi: 10.1038/nrm4074.

Abstract

Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway that is important for very low-density lipoprotein (VLDL) production and thus energy distribution to other tissues. Having common features at their promoter regions, lipogenic genes are coordinately regulated at the transcriptional level. Transcription factors, such as upstream stimulatory factors (USFs), sterol regulatory element-binding protein 1C (SREBP1C), liver X receptors (LXRs) and carbohydrate-responsive element-binding protein (ChREBP) have crucial roles in this process. Recently, insights have been gained into the signalling pathways that regulate these transcription factors. After feeding, high blood glucose and insulin levels activate lipogenic genes through several pathways, including the DNA-dependent protein kinase (DNA-PK), atypical protein kinase C (aPKC) and AKT-mTOR pathways. These pathways control the post-translational modifications of transcription factors and co-regulators, such as phosphorylation, acetylation or ubiquitylation, that affect their function, stability and/or localization. Dysregulation of lipogenesis can contribute to hepatosteatosis, which is associated with obesity and insulin resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • DNA-Activated Protein Kinase / metabolism
  • Fatty Acids / biosynthesis*
  • Gene Expression Regulation
  • Lipogenesis / genetics*
  • Lipogenesis / physiology
  • Lipoproteins, VLDL / biosynthesis*
  • Liver / metabolism*
  • Liver X Receptors
  • Mice
  • Nuclear Proteins / metabolism
  • Orphan Nuclear Receptors / metabolism
  • Protein Kinase C / metabolism
  • Protein Processing, Post-Translational / physiology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics*
  • Upstream Stimulatory Factors / metabolism

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Fatty Acids
  • Lipoproteins, VLDL
  • Liver X Receptors
  • Mlxipl protein, mouse
  • Nuclear Proteins
  • Orphan Nuclear Receptors
  • Sterol Regulatory Element Binding Protein 1
  • Transcription Factors
  • Upstream Stimulatory Factors
  • TOR Serine-Threonine Kinases
  • DNA-Activated Protein Kinase
  • Proto-Oncogene Proteins c-akt
  • PKC-3 protein
  • Protein Kinase C