Transcriptional regulation of hepatic lipogenesis.
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.
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Yuhui
Y
Wang
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Jose
J
Viscarra
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Sun-Joong
SJ
Kim
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California 94720, USA.
Hei Sook
HS
Sul
D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D050155:Lipogenesis / Q000235:genetics* / Q000502:physiology; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D000071518:Liver X Receptors; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D051720:Upstream Stimulatory Factors / Q000378:metabolism
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D005227:Fatty Acids; D008079:Lipoproteins, VLDL; D000071518:Liver X Receptors; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D057093:Orphan Nuclear Receptors; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D051747:DNA-Activated Protein Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; C115015:PKC-3 protein; D011493:Protein Kinase C