SREBPs (Sterol Regulatory Element Binding Proteins) discovered in 1993, are transcription factors that regulate the expression of genes involved with cholesterol and fatty acid metabolism. Lipogenic gene expression is influenced by various nutrients and hormones via the SREBPs. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11603-7.  Three SREBPs are described: SREBP-1a, SREBP-1c, SREBP-2.

SREBP-1 has different roles in the liver and adipose tissue. SREBP-1 increase the expression of  genes connected with lipogenesis in the liver, Genes Dev. 1998 Oct 15;12(20):3182-94.  while in the adipose tissue, no effect is noted on lipogenetic genes implicated in fatty acid and triglyceride synthesis. SREBP-1 may decrease the expression of the adipogenic transcription factors namely PPAR γ and CCAAT enhancer binding protein (C/EBPα). While the actions of SREBP-1 in the liver is becoming clearer, the exact role of SREBP-1 in adipose tissue remains to be elucidated.
SREBP-1 is thought to mediate the insulin and glucose- mediated lipogenic gene expression in the liver. Insulin stimulates SREBP-1 mRNA expression in adipocytes, J Clin Invest. 1998 Jan 1;101(1):1-9.   and increases transcriptional activation by SREBP-1. J Biol Chem. 2000 Oct 27;275(43):33302-7.   Glucose, like insulin stimulates SREBP-1 promoter activity and mRNA expression. J Biol Chem. 2000 Oct 6;275(40):31069-77.

PUFA (polyunsaturated fatty acids) decrease lipogenesis by suppressing gene expression of fatty acid synthase  in the liver. J Lipid Res. 1994 Jun;35(6):1076-84   This down-regulation of gene expression is achieved by inhibiting the m-RNA expression of SREBP-1.

When cellular levels of free cholesterol are high, SREBP-2 remains bound to the endoplasmic reticulum. When cholesterol levels fall, SREBP-2, is cleaved and translocated into the nucleus, where it binds to a sterol response element in the promoter region of target genes, activating their transcription.  SREBP-2 increases the expression of genes involved in cholesterol metabolism, namely, LDL receptor, farnesyl pyrophosphate synthase and HMG-CoA reductase.

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