1.Function and tissue distribution of SREBPs SREBPs are basic helix-loop-helix-leucine zipper (bHLH) type transcription factors and have membrane-bound characteristics, which are important gene transcription factors for the regulation of fatty acid, cholesterol and triglyceride synthesis enzymes. The membrane-bound transcription factors, SREBPs, are synthesized and retained on the rough endoplasmic reticulum, and when the amount of intracellular sterols decreases, the N-terminal bHLH portion breaks off and migrates toward the nucleus to bind to target genes in the nucleus to promote transcription of various genes associated with lipid metabolism. Up to now, three independent types of SREBPs, SREBP1a, SREBP1c and SREBP2, have their structures and characteristics clearly defined.
2. SREBPs and fatty liver The development of fatty liver is due to: (1) increased transport of free fatty acids (FFA) to the liver; (2) increased synthesis of FFA in the liver; (3) impaired β-oxidation of FFA; (4) impaired synthesis or secretion of very low density lipoproteins. It is now believed that adipocyte differentiation is regulated by a combination of SREBP1/ADD1 and peroxisome proliferator-activated receptor (PPARγ), a transcription factor that controls the transcription of genes important for maintaining cholesterol and fatty acid biobalance. The current study clearly confirms that SREBP1 plays a critical role in the development of fatty liver in leptin-deficient obese mice (Lepob/ob).SREBP1 splitting causes knockdown of lipid genes in the liver (battery) and a significant reduction in their expression, suggesting that SREBP1 controls triglyceride accumulation in the liver by regulating the level of adipogenic enzyme expression. In several mouse models including SREBP1a and SREBP 1c transgenic mice, overexpression of SREBP1 induced an increase in adipogenic enzymes and caused fatty liver. Thus, SREBP1 is considered a key transcription factor through nutritional regulation of triglyceride and adipogenic enzyme hepatic gene expression in the liver.
3. SREBPs and insulin resistance Insulin resistance is a state in which cells and organs have low insulin sensitivity. the role of SREBPs in the cause of insulin resistance: the synthesis of neutral fat is involved by many enzymes, and the main enzymes almost always act under the regulation of gene transcription level, and one of this transcriptional regulation bearing factor is SREBP1. SREBP1c mRNA is the main transcription factor that controls the expression of adipogenic channels, and the various enzymes for neutral fat synthesis in the liver are significantly reduced in SREBP1 deficiency. enzymes were significantly reduced in SREBP1 under-damaged and hardly reduced in adipocytes, from which it can be hypothesized that the transcriptional regulation of the neutral lipid synthesis lineage is different in liver and adipose, and a significant improvement in fatty liver and insulin resistance in genetically obese (ob/ob) mice mated to produce SREBP1 under-damaged. Leptin can inhibit fatty acid biosynthetic channels by reducing SREBP1 mRNA expression (13). Increased adipogenesis has been proposed in the liver and adipose tissue of leptin-deficient mice that develop obesity, as well as obesity-related syndromes.SREBP1 in vivo experiments play a key role in the regulation of adipogenesis.SREBPs are also targets for the action of a number of hormones (leptin and insulin, among others).SREBP1 has a dramatic variability in its own amount, appearing tens of fold after food This mechanism of action is still unclear and is being investigated.