Genomes and Genes
sterol regulatory element binding protein 1
Summary: A sterol regulatory element binding protein that regulates expression of GENES involved in FATTY ACIDS metabolism and LIPOGENESIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING.
- Ruiz R, Jideonwo V, Ahn M, Surendran S, Tagliabracci V, Hou Y, et al. Sterol regulatory element-binding protein-1 (SREBP-1) is required to regulate glycogen synthesis and gluconeogenic gene expression in mouse liver. J Biol Chem. 2014;289:5510-7 pubmed publisher..In conclusion, silencing both isoforms of SREBP-1 leads to significant changes in carbohydrate metabolism and does not improve insulin resistance despite reducing steatosis in an animal model of obesity and type 2 diabetes. ..
- Yu Y, Maguire T, Alwine J. Human cytomegalovirus infection induces adipocyte-like lipogenesis through activation of sterol regulatory element binding protein 1. J Virol. 2012;86:2942-9 pubmed publisher..Our studies suggest that HCMV induces adipocyte-like lipogenesis and overrides normal sterol feedback controls in order to maintain high levels of constitutive lipid synthesis during infection...
- Moon Y, Liang G, Xie X, Frank Kamenetsky M, Fitzgerald K, Koteliansky V, et al. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012;15:240-6 pubmed publisher..Inhibition of SREBP activation has therapeutic potential for treatment of hypertriglyceridemia and fatty liver disease. ..
- Guo F, Huang C, Liao X, Wang Y, He Y, Feng R, et al. Beneficial effects of mangiferin on hyperlipidemia in high-fat-fed hamsters. Mol Nutr Food Res. 2011;55:1809-18 pubmed publisher..The results suggest that mangiferin may ameliorate hypertriglyceridemia partly by modulating the expression levels of genes involved in lipid oxidation and lipogenesis. ..
- Prade E, Tobiasch M, Hitkova I, Schäffer I, Lian F, Xing X, et al. Bile acids down-regulate caveolin-1 in esophageal epithelial cells through sterol responsive element-binding protein. Mol Endocrinol. 2012;26:819-32 pubmed publisher..These data indicate that bile acid-mediated down-regulation of Cav1 marks early changes in the squamous epithelium, which may contribute to onset of Barrett esophagus metaplasia and progression to BAC. ..
- Peterson T, Sengupta S, Harris T, Carmack A, Kang S, Balderas E, et al. mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway. Cell. 2011;146:408-20 pubmed publisher..These findings establish lipin 1 as a key component of the mTORC1-SREBP pathway. ..
- Walker A, Jacobs R, Watts J, Rottiers V, Jiang K, Finnegan D, et al. A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans. Cell. 2011;147:840-52 pubmed publisher..Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders. ..
- Kotzka J, Knebel B, Haas J, Kremer L, Jacob S, Hartwig S, et al. Preventing phosphorylation of sterol regulatory element-binding protein 1a by MAP-kinases protects mice from fatty liver and visceral obesity. PLoS ONE. 2012;7:e32609 pubmed publisher..Moreover, preventing phosphorylation of SREBP-1a protects mice also from dyslipidemia. In conclusion, phosphorylation of SREBP-1a by ERK, JNK and p38 MAPK-families resembles a biological principle and plays a significant role, in vivo. ..
- Cai K, Sewer M. cAMP-stimulated transcription of DGK? requires steroidogenic factor 1 and sterol regulatory element binding protein 1. J Lipid Res. 2013;54:2121-32 pubmed publisher..SF1 and sterol regulatory element binding protein 1 (SREBP1) increased the transcriptional activity of a reporter plasmid containing 1...
- Jeon T, Osborne T. SREBPs: metabolic integrators in physiology and metabolism. Trends Endocrinol Metab. 2012;23:65-72 pubmed publisher..This review focuses on recent advances and new roles for mammalian SREBPs in physiology and metabolism. ..
- Kotzka J, Knebel B, Janssen O, Schaefer J, Soufi M, Jacob S, et al. Identification of a gene variant in the master regulator of lipid metabolism SREBP-1 in a family with a novel form of severe combined hypolipidemia. Atherosclerosis. 2011;218:134-43 pubmed publisher..Phosphorylation of SREBP-1, the master regulator of genes for central rate limiting enzymes of cholesterol and lipid metabolism, appears to be a biological principle with clinical implications. ..
- Awazawa M, Ueki K, Inabe K, Yamauchi T, Kaneko K, Okazaki Y, et al. Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway. Biochem Biophys Res Commun. 2009;382:51-6 pubmed publisher..These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis. ..
- Pettinelli P, Videla L. Up-regulation of PPAR-gamma mRNA expression in the liver of obese patients: an additional reinforcing lipogenic mechanism to SREBP-1c induction. J Clin Endocrinol Metab. 2011;96:1424-30 pubmed publisher..51; P < 0.001) levels in serum. PPAR-? is up-regulated in the liver of obese patients with NAFLD, representing an additional reinforcing lipogenic mechanism to SREBP-1c induction in the development of hepatic steatosis. ..
- Li R, Chen W, Li Y, Zhang Y, Chen G. Retinoids synergized with insulin to induce Srebp-1c expression and activated its promoter via the two liver X receptor binding sites that mediate insulin action. Biochem Biophys Res Commun. 2011;406:268-72 pubmed publisher..The RA- and insulin-induced Srebp-1c expression converged at the same sites in its promoter, indicating the roles of vitamin A in regulation of hepatic gene expression...
- Hao Q, Hansen J, Petersen R, Hallenborg P, Jørgensen C, Cinti S, et al. ADD1/SREBP1c activates the PGC1-alpha promoter in brown adipocytes. Biochim Biophys Acta. 2010;1801:421-9 pubmed publisher..In conclusion, our data demonstrate a novel role of ADD1/SREBP1c as a regulator of PGC1alpha expression in brown adipose tissue. ..
- Elam M, Yellaturu C, HOWELL G, Deng X, Cowan G, Kumar P, et al. Dysregulation of sterol regulatory element binding protein-1c in livers of morbidly obese women is associated with altered suppressor of cytokine signaling-3 and signal transducer and activator of transcription-1 signaling. Metabolism. 2010;59:587-98 pubmed publisher
- Taghibiglou C, Martin H, Lai T, Cho T, Prasad S, Kojic L, et al. Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries. Nat Med. 2009;15:1399-406 pubmed publisher..Our study suggests that agents that reduce SREBP-1 activation such as Indip may represent a new class of neuroprotective therapeutics against stroke. ..
- Ferre P, Foufelle F. Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes Metab. 2010;12 Suppl 2:83-92 pubmed publisher..ER is thus a new partner in steatosis and metabolic syndrome which is worth considering as a potential therapeutic target. ..
- Seo Y, Chong H, Infante A, Im S, Xie X, Osborne T. Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif. Proc Natl Acad Sci U S A. 2009;106:13765-9 pubmed publisher..SREBP-1 bound not only to many well-characterized SREBP-1 target genes but to several other previously unknown targets in lipid and carbohydrate metabolism as well as many putative target genes in other diverse biological pathways. ..
- Li Y, Xu S, Mihaylova M, Zheng B, Hou X, Jiang B, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13:376-388 pubmed publisher..AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis. ..
- Dervishi E, Serrano C, Joy M, Serrano M, Rodellar C, Calvo J. Effect of the feeding system on the fatty acid composition, expression of the Delta9-desaturase, Peroxisome Proliferator-Activated Receptor Alpha, Gamma, and Sterol Regulatory Element Binding Protein 1 genes in the semitendinous muscle of light lambs. BMC Vet Res. 2010;6:40 pubmed publisher..The data indicated that the feeding system is the main factor affecting the fatty acid composition and SCD gene expression, which is also affected by CLA and possibly by n-6/n-3 PUFAs. ..
- De Gottardi A, Spahr L, Ravier Dall Antonia F, Hadengue A. Cannabinoid receptor 1 and 2 agonists increase lipid accumulation in hepatocytes. Liver Int. 2010;30:1482-9 pubmed publisher..Not only CB1 but also CB2 participated in the regulation of lipid metabolism in human-derived immortalized hepatocytes by regulating the expression of key enzymes of lipid synthesis and transport. ..
- Najafi Shoushtari S, Kristo F, Li Y, Shioda T, Cohen D, Gerszten R, et al. MicroRNA-33 and the SREBP host genes cooperate to control cholesterol homeostasis. Science. 2010;328:1566-9 pubmed publisher..Our findings indicate that miR-33 acts in concert with the SREBP host genes to control cholesterol homeostasis and suggest that miR-33 may represent a therapeutic target for ameliorating cardiometabolic diseases...
- Zhang Y, Chen W, Li R, Li Y, Ge Y, Chen G. Insulin-regulated Srebp-1c and Pck1 mRNA expression in primary hepatocytes from zucker fatty but not lean rats is affected by feeding conditions. PLoS ONE. 2011;6:e21342 pubmed publisher..This impairment can be partially restored in hepatocytes from ZF rats after an overnight fasting, a phenomenon that deserves further investigation. ..
- Yellaturu C, Deng X, Park E, Raghow R, Elam M. Insulin enhances the biogenesis of nuclear sterol regulatory element-binding protein (SREBP)-1c by posttranscriptional down-regulation of Insig-2A and its dissociation from SREBP cleavage-activating protein (SCAP).SREBP-1c complex. J Biol Chem. 2009;284:31726-34 pubmed publisher..Thus, insulin-induced reduction in Insig-2a protein leads to an enhanced export of the SCAP.SREBP-1c complex from ER to the Golgi. ..
- Damiano F, Alemanno S, Gnoni G, Siculella L. Translational control of the sterol-regulatory transcription factor SREBP-1 mRNA in response to serum starvation or ER stress is mediated by an internal ribosome entry site. Biochem J. 2010;429:603-12 pubmed publisher..Overall, these findings indicate that the presence of IRES in the SREBP-1a 5'-UTR allows translation to be maintained under conditions that are inhibitory to cap-dependent translation. ..
- Im S, Hammond L, Yousef L, Nugas Selby C, Shin D, Seo Y, et al. Sterol regulatory element binding protein 1a regulates hepatic fatty acid partitioning by activating acetyl coenzyme A carboxylase 2. Mol Cell Biol. 2009;29:4864-72 pubmed publisher..Our chromatin immunoprecipitation results support this hypothesis. ..
- Kammoun H, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009;119:1201-15 pubmed publisher..These findings demonstrate that GRP78 inhibits both insulin-dependent and ER stress-dependent SREBP-1c proteolytic cleavage and explain the role of ER stress in hepatic steatosis in obese rodents. ..
- Lecomte V, Meugnier E, Euthine V, Durand C, Freyssenet D, Nemoz G, et al. A new role for sterol regulatory element binding protein 1 transcription factors in the regulation of muscle mass and muscle cell differentiation. Mol Cell Biol. 2010;30:1182-98 pubmed publisher..Our findings identify a new role for SREBP-1 transcription factors in muscle, thus linking the control of muscle mass to metabolic pathways. ..
- Düvel K, Yecies J, Menon S, Raman P, Lipovsky A, Souza A, et al. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell. 2010;39:171-83 pubmed publisher..Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease. ..
- Conte G, Mele M, Chessa S, Castiglioni B, Serra A, Pagnacco G, et al. Diacylglycerol acyltransferase 1, stearoyl-CoA desaturase 1, and sterol regulatory element binding protein 1 gene polymorphisms and milk fatty acid composition in Italian Brown cattle. J Dairy Sci. 2010;93:753-63 pubmed publisher..However, the unbalanced distribution of alleles in all polymorphisms investigated suggested that the size of population should be increased to confirm the results of the present study. ..
- Sato R. Sterol metabolism and SREBP activation. Arch Biochem Biophys. 2010;501:177-81 pubmed publisher..Sterol metabolites, including cholesterol, 24,25-dihydrolanosterol and oxysterols, strongly participate in the regulation of sterol metabolism via binding to its particular proteins. ..
- Wendel A, Li L, Li Y, Cline G, Shulman G, Coleman R. Glycerol-3-phosphate acyltransferase 1 deficiency in ob/ob mice diminishes hepatic steatosis but does not protect against insulin resistance or obesity. Diabetes. 2010;59:1321-9 pubmed publisher..In ob/ob mice, sterol regulatory element binding protein 1 (SREBP1) mediates the induction of steatosis by upregulating target genes, including glycerol-3-..
- Shao S, Fang Z, Yu X, Zhang M. Transcription factors involved in glucose-stimulated insulin secretion of pancreatic beta cells. Biochem Biophys Res Commun. 2009;384:401-4 pubmed publisher..The related molecular mechanisms are analyzed as well. Furthermore, the association between the role of transcription factors in GSIS and the development of T2DM is discussed. ..
- Kammoun H, Hainault I, Ferre P, Foufelle F. Nutritional related liver disease: targeting the endoplasmic reticulum stress. Curr Opin Clin Nutr Metab Care. 2009;12:575-82 pubmed publisher..However, as ER stress is a fundamental mechanism involved in cell survival, any modification of this pathway must be carefully assessed. ..
- Guo D, Prins R, Dang J, Kuga D, Iwanami A, Soto H, et al. EGFR signaling through an Akt-SREBP-1-dependent, rapamycin-resistant pathway sensitizes glioblastomas to antilipogenic therapy. Sci Signal. 2009;2:ra82 pubmed publisher..These results identify a previously undescribed EGFR-mediated prosurvival metabolic pathway and suggest new therapeutic approaches to treating EGFR-activated glioblastomas. ..
- Shao S, Liu Z, Yang Y, Zhang M, Yu X. SREBP-1c, Pdx-1, and GLP-1R involved in palmitate-EPA regulated glucose-stimulated insulin secretion in INS-1 cells. J Cell Biochem. 2010;111:634-42 pubmed publisher..These results suggested that sequent SREBP-1c-Pdx-1-GLP-1R signal pathway was involved in the palmitate-caused GSIS impairment in beta cells. ..
- Walker A, Yang F, Jiang K, Ji J, Watts J, Purushotham A, et al. Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. Genes Dev. 2010;24:1403-17 pubmed publisher..These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis. ..
- Kotzka J, Knebel B, Avci H, Jacob S, Nitzgen U, Jockenhovel F, et al. Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes. Atherosclerosis. 2010;213:156-65 pubmed publisher..These experiments emphasize the role SREBP-1a and its phosphorylation for gene regulatory effects of GH. ..
- Hu X, Wang Y, Wang J, Xue Y, Li Z, Nagao K, et al. Dietary saponins of sea cucumber alleviate orotic acid-induced fatty liver in rats via PPARalpha and SREBP-1c signaling. Lipids Health Dis. 2010;9:25 pubmed publisher..Therefore, the present study was undertaken to examine the effect of saponins extracted from sea cucumber (Pearsonothuria graeffei) on the preventive activity of fatty liver in rats...
- Okazaki H, Goldstein J, Brown M, Liang G. LXR-SREBP-1c-phospholipid transfer protein axis controls very low density lipoprotein (VLDL) particle size. J Biol Chem. 2010;285:6801-10 pubmed publisher..In the absence of LDL receptors, the large VLDLs accumulate and produce massive hypertriglyceridemia. ..
- Tanaka N, Zhang X, Sugiyama E, Kono H, Horiuchi A, Nakajima T, et al. Eicosapentaenoic acid improves hepatic steatosis independent of PPAR? activation through inhibition of SREBP-1 maturation in mice. Biochem Pharmacol. 2010;80:1601-12 pubmed publisher..These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPAR? activation and ensuing augmentation of hepatic oxidative stress. ..
- Ponugoti B, Kim D, Xiao Z, Smith Z, Miao J, Zang M, et al. SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism. J Biol Chem. 2010;285:33959-70 pubmed publisher..Reducing acetylation of SREBP-1c by targeting SIRT1 may be useful for treating metabolic disorders, including fatty liver, obesity, and type II diabetes...
- Dubuquoy C, Robichon C, Lasnier F, Langlois C, Dugail I, Foufelle F, et al. Distinct regulation of adiponutrin/PNPLA3 gene expression by the transcription factors ChREBP and SREBP1c in mouse and human hepatocytes. J Hepatol. 2011;55:145-53 pubmed publisher..All together, our results suggest that adiponutrin/PNPLA3 is regulated by two key factors of the glycolytic and lipogenic pathways, raising the question of its implication in the metabolism of carbohydrates and lipids. ..
- Sajan M, Standaert M, Rivas J, Miura A, Kanoh Y, Soto J, et al. Role of atypical protein kinase C in activation of sterol regulatory element binding protein-1c and nuclear factor kappa B (NFkappaB) in liver of rodents used as a model of diabetes, and relationships to hyperlipidaemia and insulin resistance. Diabetologia. 2009;52:1197-207 pubmed publisher..Excessive hepatic aPKC-dependent activation of SREBP-1c and NFkappaB may contribute importantly to hyperlipidaemia and systemic insulin resistance. ..
- Angelakis E, Bastelica D, Ben Amara A, El Filali A, Dutour A, Mege J, et al. An evaluation of the effects of Lactobacillus ingluviei on body weight, the intestinal microbiome and metabolism in mice. Microb Pathog. 2012;52:61-8 pubmed publisher..The inoculation of L. ingluviei in mice resulted in alterations in the intestinal flora, increased weight gain and liver enlargement, accelerated metabolism and increased inflammation. ..
- Ishimoto K. [Lipin 1 in lipid metabolism]. Yakugaku Zasshi. 2011;131:1189-94 pubmed..Through two distinct functions in the nucleus and cytosol, lipin 1 modulates lipid metabolism and glucose homeostasis. Here we will discuss recent developments in our understanding of the role of lipin 1 in lipid metabolism. ..
- Han C, Vinsky M, Aldai N, Dugan M, McAllister T, Li C. Association analyses of DNA polymorphisms in bovine SREBP-1, LXR?, FADS1 genes with fatty acid composition in Canadian commercial crossbred beef steers. Meat Sci. 2013;93:429-36 pubmed publisher..05). Further studies are needed to validate the associations and to delineate the roles of the gene polymorphisms in determining the fatty acid composition in beef tissues. ..
- Carobbio S, Hagen R, Lelliott C, Slawik M, Medina Gomez G, Tan C, et al. Adaptive changes of the Insig1/SREBP1/SCD1 set point help adipose tissue to cope with increased storage demands of obesity. Diabetes. 2013;62:3697-708 pubmed publisher..These adaptive mechanisms contribute to maintain lipid desaturation through preferential SCD1 regulation and facilitate fat storage in WAT, despite on-going metabolic stress. ..
- Chujo Y, Fujii N, Okita N, Konishi T, Narita T, Yamada A, et al. Caloric restriction-associated remodeling of rat white adipose tissue: effects on the growth hormone/insulin-like growth factor-1 axis, sterol regulatory element binding protein-1, and macrophage infiltration. Age (Dordr). 2013;35:1143-56 pubmed publisher..Our findings suggest that CR-associated remodeling of WAT, which involves SREBP-1-mediated transcriptional activation and suppression of macrophage infiltration, is regulated in a GH-IGF-1-independent manner. ..
- Shi L, Shi L, Song G, Zhang H, Hu Z, Wang C, et al. Oxymatrine attenuates hepatic steatosis in non-alcoholic fatty liver disease rats fed with high fructose diet through inhibition of sterol regulatory element binding transcription factor 1 (Srebf1) and activation of peroxisome proliferator activated . Eur J Pharmacol. 2013;714:89-95 pubmed publisher