[Lipid synthetic transcription factor, SREBP].
SREBP family have been recently established as bHLH type transcription factors governing lipid synthesis. While SREBP-2 regulates expression of genes involved in cholesterol biosynthesis and LDL receptor, SREBP-1c controls fatty acid synthesis. Cellular cholesterol is regulated by feedback system where SCAP/Insig system regulates cleavage of SREBP-2 for its activation depending upon cellular cholesterol demand. Meanwhile, SREBP-1c is nutritionally regulated, excess energy intake could activate hepatic SREBP-1c expression leading to formation of remnant lipoproteins and hepatic insulin resistance through suppression of IRS-2 expression. Hepatic SREBP-1c could be deeply involved in metabolic syndrome. Thus, SREBP-1c could be a therapeutic target to treat metabolic syndrome. Polyunsaturated fatty acids suppress SREBP-1c and suppress lipogenesis.
Hitoshi
Shimano
S
Department of Internal Medicine (Metabolism & Endocrinology), Graduate School of Comprehensive Human Sciences, University of Tsukuba.
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D002149:Energy Intake / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology; D024821:Metabolic Syndrome / Q000209:etiology / Q000628:therapy; D010750:Phosphoproteins / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005231:Fatty Acids, Unsaturated; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008055:Lipids; D008565:Membrane Proteins; D010750:Phosphoproteins; D011973:Receptors, LDL; C497387:SREBF1 protein, human; C497390:SREBF2 protein, human; C102196:SREBP cleavage-activating protein; D051780:Sterol Regulatory Element Binding Protein 1; D051782:Sterol Regulatory Element Binding Protein 2; D014157:Transcription Factors