Genomes and Genes
stearoyl coa desaturase
Summary: An enzyme that catalyzes the formation of oleoyl-CoA, A, and water from stearoyl-CoA, AH2, and oxygen where AH2 is an unspecified hydrogen donor.
- Peter A, Weigert C, Staiger H, Rittig K, Cegan A, Lutz P, et al. Induction of stearoyl-CoA desaturase protects human arterial endothelial cells against lipotoxicity. Am J Physiol Endocrinol Metab. 2008;295:E339-49 pubmed publisher..These findings add a novel aspect to the atheroprotective actions of LXR activators in cardiovascular disease. ..
- Collins J, Neville M, Hoppa M, Frayn K. De novo lipogenesis and stearoyl-CoA desaturase are coordinately regulated in the human adipocyte and protect against palmitate-induced cell injury. J Biol Chem. 2010;285:6044-52 pubmed publisher..DNL may not act primarily to increase fat stores but may serve as a key regulator, in tandem with elongation and desaturation, to maintain cell membrane fluidity and insulin sensitivity within the human adipocyte. ..
- Hebbachi A, Knight B, Wiggins D, Patel D, Gibbons G. Peroxisome proliferator-activated receptor alpha deficiency abolishes the response of lipogenic gene expression to re-feeding: restoration of the normal response by activation of liver X receptor alpha. J Biol Chem. 2008;283:4866-76 pubmed..We conclude that intact PPARalpha is required to mediate the response of Scd-1 and Fas gene expression to insulin and that this is normally achieved directly by activation of LXRalpha. ..
- Kakuma T, Lee Y, Unger R. Effects of leptin, troglitazone, and dietary fat on stearoyl CoA desaturase. Biochem Biophys Res Commun. 2002;297:1259-63 pubmed..To determine if they affect the expression of stearoyl CoA desaturase (SCD)-1 and -2, their mRNA was measured in livers of normal, hyperleptinemic, troglitazone-treated, and ..
- Miyazaki M, Dobrzyn A, Man W, Chu K, Sampath H, Kim H, et al. Stearoyl-CoA desaturase 1 gene expression is necessary for fructose-mediated induction of lipogenic gene expression by sterol regulatory element-binding protein-1c-dependent and -independent mechanisms. J Biol Chem. 2004;279:25164-71 pubmed
- Liu X, Miyazaki M, Flowers M, Sampath H, Zhao M, Chu K, et al. Loss of Stearoyl-CoA desaturase-1 attenuates adipocyte inflammation: effects of adipocyte-derived oleate. Arterioscler Thromb Vasc Biol. 2010;30:31-8 pubmed publisher..Loss of SCD1 attenuates adipocyte inflammation and its paracrine regulation of inflammation in macrophages and endothelial cells. The reduced oleate level is linked to the inflammation-modulating effects of SCD1 deficiency. ..
- Warensjo E, Ingelsson E, Lundmark P, Lannfelt L, Syvanen A, Vessby B, et al. Polymorphisms in the SCD1 gene: associations with body fat distribution and insulin sensitivity. Obesity (Silver Spring). 2007;15:1732-40 pubmed..These results need confirmation in other populations with a larger sample size. ..
- Dobrzyn P, Sampath H, Dobrzyn A, Miyazaki M, Ntambi J. Loss of stearoyl-CoA desaturase 1 inhibits fatty acid oxidation and increases glucose utilization in the heart. Am J Physiol Endocrinol Metab. 2008;294:E357-64 pubmed..This increase in cardiac insulin sensitivity and glucose utilization due to SCD1 deficiency could prove therapeutic in pathological conditions such as obesity that are characterized by skewed cardiac substrate utilization. ..
- Rahman S, Dobrzyn A, Dobrzyn P, Lee S, Miyazaki M, Ntambi J. Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. Proc Natl Acad Sci U S A. 2003;100:11110-5 pubmed..We hypothesize that loss of SCD1 function induces increased insulin signaling at least in part by a reduction in the expression of protein-tyrosine phosphatase 1B. SCD1 could be a therapeutic target in the treatment of diabetes. ..
- Caspi A, Williams B, Kim Cohen J, Craig I, Milne B, Poulton R, et al. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proc Natl Acad Sci U S A. 2007;104:18860-5 pubmed..The finding shows that environmental exposures can be used to uncover novel candidate genes in complex phenotypes. It also shows that genes may work via the environment to shape the IQ, helping to close the nature versus nurture debate. ..
- Mele M, Conte G, Castiglioni B, Chessa S, Macciotta N, Serra A, et al. Stearoyl-coenzyme A desaturase gene polymorphism and milk fatty acid composition in Italian Holsteins. J Dairy Sci. 2007;90:4458-65 pubmed
- Scaglia N, Caviglia J, Igal R. High stearoyl-CoA desaturase protein and activity levels in simian virus 40 transformed-human lung fibroblasts. Biochim Biophys Acta. 2005;1687:141-51 pubmed..The strong correlation of high levels of MUFA and neoplastic phenotype suggest that the regulation of stearoyl CoA desaturase (SCD) must play a significant role in cancer development...
- Sampath H, Miyazaki M, Dobrzyn A, Ntambi J. Stearoyl-CoA desaturase-1 mediates the pro-lipogenic effects of dietary saturated fat. J Biol Chem. 2007;282:2483-93 pubmed..SCD1 thus serves as a molecular switch in the promotion or prevention of lipid-induced disorders brought on by consumption of excess saturated fat. ..
- Mar Heyming R, Miyazaki M, Weissglas Volkov D, Kolaitis N, Sadaat N, Plaisier C, et al. Association of stearoyl-CoA desaturase 1 activity with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2008;28:1193-9 pubmed publisher..002). Our results demonstrate that the fatty acid desaturation index is a highly heritable trait that is associated with the dyslipidemia observed in FCHL. ..
- Ntambi J, Miyazaki M, Dobrzyn A. Regulation of stearoyl-CoA desaturase expression. Lipids. 2004;39:1061-5 pubmed..By using SCD1-/- mice, which are deficient in tissue oleate, we begin to learn more about the physiological role of SCD gene expression and oleate in normal and disease states. ..
- Van Gilst M, Hadjivassiliou H, Yamamoto K. A Caenorhabditis elegans nutrient response system partially dependent on nuclear receptor NHR-49. Proc Natl Acad Sci U S A. 2005;102:13496-501 pubmed..Our characterization of a fasting response system and our finding that nhr-49 regulates a sector within this system provide insight into the mechanisms by which animals respond to nutritional signals. ..
- Attie A, Krauss R, Gray Keller M, Brownlie A, Miyazaki M, Kastelein J, et al. Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia. J Lipid Res. 2002;43:1899-907 pubmed..We propose that many of the factors that influence plasma triglyceride levels do so by converging upon the regulation of SCD activity. ..
- Miyazaki M, Kim Y, Ntambi J. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis. J Lipid Res. 2001;42:1018-24 pubmed..These observations demonstrate that induction of triglyceride synthesis is highly dependent on SCD1 gene expression. ..
- Ntambi J, Miyazaki M. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog Lipid Res. 2004;43:91-104 pubmed
- Cohen P, Miyazaki M, Socci N, Hagge Greenberg A, Liedtke W, Soukas A, et al. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Science. 2002;297:240-3 pubmed..These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions. ..
- Koltun D, Parkhill E, Vasilevich N, Glushkov A, Zilbershtein T, Ivanov A, et al. Novel, potent, selective, and metabolically stable stearoyl-CoA desaturase (SCD) inhibitors. Bioorg Med Chem Lett. 2009;19:2048-52 pubmed publisher..The most potent analog (8g) had IC(50) value of 50 pM in a HEPG2 SCD assay and has been shown to be metabolically stable and selective against Delta5 and Delta6 desaturases. ..
- Falvella F, Pascale R, Gariboldi M, Manenti G, De Miglio M, Simile M, et al. Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with genetic predisposition to hepatocarcinogenesis in mice and rats. Carcinogenesis. 2002;23:1933-6 pubmed..These results suggest that the Scd1 gene represents a downstream target of hepatocellular tumor-modifier loci in two rodent species. ..
- Daniel Z, Wynn R, Salter A, Buttery P. Differing effects of forage and concentrate diets on the oleic acid and conjugated linoleic acid content of sheep tissues: the role of stearoyl-CoA desaturase. J Anim Sci. 2004;82:747-58 pubmed..By contrast, the increased concentration of CLA in animals fed forage-based diets is associated with an increase in substrate (C18:1 trans-11) availability. ..
- Binczek E, Jenke B, Holz B, Günter R, Thevis M, Stoffel W. Obesity resistance of the stearoyl-CoA desaturase-deficient (scd1-/-) mouse results from disruption of the epidermal lipid barrier and adaptive thermoregulation. Biol Chem. 2007;388:405-18 pubmed..Finally, the occurrence of SCD1 and a newly described hSCD5 (ACOD4) gene in humans suggests that the scd1-/- mouse mutant might be a valuable animal model for the study of human skin diseases associated with epidermal barrier defects. ..
- Taniguchi M, Utsugi T, Oyama K, Mannen H, Kobayashi M, Tanabe Y, et al. Genotype of stearoyl-coA desaturase is associated with fatty acid composition in Japanese Black cattle. Mamm Genome. 2004;15:142-8 pubmed..Transcription factors such as sterol regulatory element binding protein-1c (SREBP-1c) may account for the remaining part of the genetic variation in fatty acid composition. ..
- Peter A, Weigert C, Staiger H, Machicao F, Schick F, Machann J, et al. Individual stearoyl-coa desaturase 1 expression modulates endoplasmic reticulum stress and inflammation in human myotubes and is associated with skeletal muscle lipid storage and insulin sensitivity in vivo. Diabetes. 2009;58:1757-65 pubmed publisher..This may describe individuals with increased capability of innoxious free fatty acid handling and benign triglyceride storage. ..
- Velasco A, Tabernero A, Medina J. Role of oleic acid as a neurotrophic factor is supported in vivo by the expression of GAP-43 subsequent to the activation of SREBP-1 and the up-regulation of stearoyl-CoA desaturase during postnatal development of the brain. Brain Res. 2003;977:103-11 pubmed..In conclusion, our results support the hypothesis that the synthesis of oleic acid is linked to neuronal differentiation during rat brain development. ..
- Ntambi J, Miyazaki M. Recent insights into stearoyl-CoA desaturase-1. Curr Opin Lipidol. 2003;14:255-61 pubmed..SCD1, therefore, appears to be an important metabolic control point, and inhibition of its expression could be of benefit for the treatment of obesity, diabetes and other metabolic diseases. ..
- Warensjo E, Riserus U, Vessby B. Fatty acid composition of serum lipids predicts the development of the metabolic syndrome in men. Diabetologia. 2005;48:1999-2005 pubmed..Our results suggest a role of dietary fat quality in the development of metabolic syndrome, but the possibility that altered fatty acid composition, partly secondary to genetic or hormonal factors, should also be considered. ..
- Liu G. Stearoyl-CoA desaturase inhibitors: update on patented compounds. Expert Opin Ther Pat. 2009;19:1169-91 pubmed publisher..Between January 2005 and February 2009, there were approximately 70 SCD1 inhibitor patent applications published. ..
- Paton C, Ntambi J. Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab. 2009;297:E28-37 pubmed publisher..In this article, we summarize the recent and timely advances concerning the important role of SCD in the biochemistry and physiology of lipid metabolism. ..
- Koltun D, Vasilevich N, Parkhill E, Glushkov A, Zilbershtein T, Mayboroda E, et al. Orally bioavailable, liver-selective stearoyl-CoA desaturase (SCD) inhibitors. Bioorg Med Chem Lett. 2009;19:3050-3 pubmed publisher..We describe the discovery of 4a from HTS hit 1 followed by scaffold replacement and SAR studies focused on DMPK properties. ..
- Flowers J, Rabaglia M, Schueler K, Flowers M, Lan H, Keller M, et al. Loss of stearoyl-CoA desaturase-1 improves insulin sensitivity in lean mice but worsens diabetes in leptin-deficient obese mice. Diabetes. 2007;56:1228-39 pubmed..Therefore, although loss of Scd1 has beneficial effects on adiposity, this benefit may come at the expense of beta-cells, resulting in an increased risk of diabetes. ..
- Hulver M, Berggren J, Carper M, Miyazaki M, Ntambi J, Hoffman E, et al. Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans. Cell Metab. 2005;2:251-61 pubmed..These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. ..
- Ariyama H, Kono N, Matsuda S, Inoue T, Arai H. Decrease in membrane phospholipid unsaturation induces unfolded protein response. J Biol Chem. 2010;285:22027-35 pubmed publisher..Finally we showed that palmitic acid-induced UPR was significantly enhanced by LPCAT3 knockdown as well as SCD1 knockdown. These results suggest that a decrease in membrane phospholipid unsaturation induces UPR. ..
- Dobrzyn P, Dobrzyn A, Miyazaki M, Cohen P, Asilmaz E, Hardie D, et al. Stearoyl-CoA desaturase 1 deficiency increases fatty acid oxidation by activating AMP-activated protein kinase in liver. Proc Natl Acad Sci U S A. 2004;101:6409-14 pubmed..001) thereby stimulating the oxidation of mitochondrial palmitoyl-CoA. Our results identify AMPK as a mediator of increased fatty acid oxidation in liver of SCD1-deficient mice. ..
- Riserus U, Tan G, Fielding B, Neville M, Currie J, Savage D, et al. Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma. Diabetes. 2005;54:1379-84 pubmed..The restored SCD activity index after rosiglitazone in PPARgamma mutation supports a pivotal role of PPARgamma function in SCD regulation. ..
- Voss M, Beha A, Tennagels N, Tschank G, Herling A, Quint M, et al. Gene expression profiling in skeletal muscle of Zucker diabetic fatty rats: implications for a role of stearoyl-CoA desaturase 1 in insulin resistance. Diabetologia. 2005;48:2622-30 pubmed..This supports the hypothesis that elevated SCD1 expression is a possible cause of insulin resistance and type 2 diabetes. ..
- Chong M, Hodson L, Bickerton A, Roberts R, Neville M, Karpe F, et al. Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr. 2008;87:817-23 pubmed..02). Expression of lipogenic genes in subcutaneous adipose tissue was not significantly affected by diet. Parallel activation of DNL and SCD was found after a short period of HC feeding. ..
- Shiwaku K, Hashimoto M, Kitajima K, Nogi A, Anuurad E, Enkhmaa B, et al. Triglyceride levels are ethnic-specifically associated with an index of stearoyl-CoA desaturase activity and n-3 PUFA levels in Asians. J Lipid Res. 2004;45:914-22 pubmed..HTG is ethnicity-specifically associated with an increase in the 18:1/18:0 ratio and a decrease in n-3 PUFA in plasma for Japanese, Koreans, and Mongolians. ..
- Miyazaki M, Dobrzyn A, Sampath H, Lee S, Man W, Chu K, et al. Reduced adiposity and liver steatosis by stearoyl-CoA desaturase deficiency are independent of peroxisome proliferator-activated receptor-alpha. J Biol Chem. 2004;279:35017-24 pubmed
- Schenk S, Horowitz J. Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest. 2007;117:1690-8 pubmed
- Biddinger S, Miyazaki M, Boucher J, Ntambi J, Kahn C. Leptin suppresses stearoyl-CoA desaturase 1 by mechanisms independent of insulin and sterol regulatory element-binding protein-1c. Diabetes. 2006;55:2032-41 pubmed..Thus, the effect of leptin on SCD1 in liver is independent of insulin and SREBP-1c, and leptin, rather than insulin, is the major regulator of hepatic MUFA synthesis in obesity-linked diabetes. ..
- Christianson J, Nicoloro S, Straubhaar J, Czech M. Stearoyl-CoA desaturase 2 is required for peroxisome proliferator-activated receptor gamma expression and adipogenesis in cultured 3T3-L1 cells. J Biol Chem. 2008;283:2906-16 pubmed..These results reveal that SCD2 is required for the induction and maintenance of PPARgamma protein levels and adipogenesis in 3T3-L1 cells. ..
- Stefan N, Peter A, Cegan A, Staiger H, Machann J, Schick F, et al. Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans. Diabetologia. 2008;51:648-56 pubmed publisher..46, p=0.02). Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity. ..
- Flowers M, Miyazaki M, Liu X, Ntambi J. Probing the role of stearoyl-CoA desaturase-1 in hepatic insulin resistance. J Clin Invest. 2006;116:1478-81 pubmed
- MacDonald M, Van Eck M, Hildebrand R, Wong B, Bissada N, Ruddle P, et al. Despite antiatherogenic metabolic characteristics, SCD1-deficient mice have increased inflammation and atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:341-7 pubmed publisher..These studies reinforce the crucial role of chronic inflammation in promoting atherosclerosis, even in the presence of antiatherogenic biochemical and metabolic characteristics. ..
- Chu K, Miyazaki M, Man W, Ntambi J. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol Cell Biol. 2006;26:6786-98 pubmed..In addition, SCD1 deficiency also increased plasma high-density lipoprotein cholesterol levels induced by LXR activation. ..
- Lai E, Bikopoulos G, Wheeler M, Rozakis Adcock M, Volchuk A. Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic beta-cells. Am J Physiol Endocrinol Metab. 2008;294:E540-50 pubmed publisher..Human islets and MIN6 cells were found to express high levels of stearoyl-CoA desaturase-1 compared with INS-1 cells, which may account for the decreased susceptibility of these cells to the cytotoxic effects of palmitate. ..
- Wang J, Yu L, Schmidt R, Su C, Huang X, Gould K, et al. Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates. Biochem Biophys Res Commun. 2005;332:735-42 pubmed..These data suggested that hSCD5 plays a role distinct from that of hSCD1 during development and in normal physiological conditions. ..