Fasn

Summary

Gene Symbol: Fasn
Description: fatty acid synthase
Alias: fatty acid synthase
Species: rat
Products:     Fasn

Top Publications

  1. Schweizer M, Takabayashi K, Laux T, Beck K, Schreglmann R. Rat mammary gland fatty acid synthase: localization of the constituent domains and two functional polyadenylation/termination signals in the cDNA. Nucleic Acids Res. 1989;17:567-86 pubmed
    The rat fatty acid synthase (FAS) is active only as a dimer, although the eight component functions are contained in a single polypeptide chain. Using mRNA from lactating rat mammary glands a cDNA expression library was established...
  2. Kim E, Kleman A, Ronnett G. Fatty acid synthase gene regulation in primary hypothalamic neurons. Neurosci Lett. 2007;423:200-4 pubmed
    ..We, and others have previously demonstrated that C75, a fatty acid synthase (FAS) inhibitor, induced significant anorexia and weight loss by both central and peripheral mechanisms...
  3. Pasta S, Witkowski A, Joshi A, Smith S. Catalytic residues are shared between two pseudosubunits of the dehydratase domain of the animal fatty acid synthase. Chem Biol. 2007;14:1377-85 pubmed
    Expression, characterization, and mutagenesis of a series of N-terminal fragments of an animal fatty acid synthase, containing the beta-ketoacyl synthase, acyl transferase, and dehydratase domains, demonstrate that the dehydratase domain ..
  4. Lomba A, Martinez J, García Díaz D, Paternain L, Marti A, Campion J, et al. Weight gain induced by an isocaloric pair-fed high fat diet: a nutriepigenetic study on FASN and NDUFB6 gene promoters. Mol Genet Metab. 2010;101:273-8 pubmed publisher
    ..Epididymal adipose tissue expression of the fatty acid synthase (FASN) gene and NADH dehydrogenase (ubiquinone) 1?-subcomplex 6 (NDUFB6) were significantly reduced in HFD ..
  5. Witkowski A, Joshi A, Rangan V, Falick A, Witkowska H, Smith S. Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit. Reevaluation of the side-by-side, antiparallel subunit model. J Biol Chem. 1999;274:11557-63 pubmed
    ..Treatment of animal fatty acid synthase dimers with dibromopropanone generates three new molecular species with decreased electrophoretic ..
  6. Asturias F, Chadick J, Cheung I, Stark H, Witkowski A, Joshi A, et al. Structure and molecular organization of mammalian fatty acid synthase. Nat Struct Mol Biol. 2005;12:225-32 pubmed
    ..synthesis of fatty acids in the cytosol of animal cells is carried out by the multifunctional, homodimeric fatty acid synthase (FAS)...
  7. Hogan J, Stephens J. The regulation of fatty acid synthase by STAT5A. Diabetes. 2005;54:1968-75 pubmed
    Growth hormone (GH) diminishes adipose tissue mass in vivo and decreases expression and activity of fatty acid synthase (FAS) in adipocytes...
  8. Schweizer M, Roder K, Zhang L, Wolf S. Transcription factors acting on the promoter of the rat fatty acid synthase gene. Biochem Soc Trans. 2002;30:1070-2 pubmed
    b>Fatty acid synthase (FAS), one of the main lipogenic enzymes, converts dietary calories into a storage form of energy...
  9. Hansmannel F, Mordier S, Iynedjian P. Insulin induction of glucokinase and fatty acid synthase in hepatocytes: analysis of the roles of sterol-regulatory-element-binding protein-1c and liver X receptor. Biochem J. 2006;399:275-83 pubmed
    ..is induced by insulin in the liver and is considered a master regulator of lipogenic genes such as FASN (fatty acid synthase)...

More Information

Publications48

  1. Xiao R, Su Y, Simmen R, Simmen F. Dietary soy protein inhibits DNA damage and cell survival of colon epithelial cells through attenuated expression of fatty acid synthase. Am J Physiol Gastrointest Liver Physiol. 2008;294:G868-76 pubmed publisher
    ..We hypothesized that decreased expression of fatty acid synthase (FASN) underlies, in part, the tumor-preventive effects of soy protein, since FASN overexpression ..
  2. Jeon B, Kim Y, Choi W, Koh D, Kim M, Yoon J, et al. Kr-pok increases FASN expression by modulating the DNA binding of SREBP-1c and Sp1 at the proximal promoter. J Lipid Res. 2012;53:755-66 pubmed publisher
    ..b>Fatty acid synthase gene (FASN) encodes one of the key enzymes in fatty acids synthesis and is the only enzyme that synthesizes ..
  3. Joshi A, Witkowski A, Smith S. Mapping of functional interactions between domains of the animal fatty acid synthase by mutant complementation in vitro. Biochemistry. 1997;36:2316-22 pubmed
    Polypeptides of the animal fatty acid synthase (FAS) consist of three amino-terminal catalytic domains, beta-ketoacyl synthase, malonyl/acetyltransacylase, and dehydrase, separated by a 600-residue structural core from four carboxyl-..
  4. Jegatheesan P, Beutheu S, Ventura G, Nubret E, Sarfati G, Bergheim I, et al. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats. J Nutr. 2015;145:2273-9 pubmed publisher
    ..Fructose caused a 2-fold increase in the gene expression of fatty acid synthase (Fas) and 70% and 90% decreases in that of carnitine palmitoyl-transferase 1a and microsomal TG transfer ..
  5. Rumberger J, Wu T, Hering M, Marshall S. Role of hexosamine biosynthesis in glucose-mediated up-regulation of lipogenic enzyme mRNA levels: effects of glucose, glutamine, and glucosamine on glycerophosphate dehydrogenase, fatty acid synthase, and acetyl-CoA carboxylase mRNA levels. J Biol Chem. 2003;278:28547-52 pubmed
    ..into adipose and liver cells is known to up-regulate mRNA levels for various lipogenic enzymes such as fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC)...
  6. Ridsdale R, Post M. Surfactant lipid synthesis and lamellar body formation in glycogen-laden type II cells. Am J Physiol Lung Cell Mol Physiol. 2004;287:L743-51 pubmed
    ..synthesis in these cells we determined the subcellular localization of two key enzymes for PC biosynthesis, fatty acid synthase (FAS) and CTP:phosphocholine cytidylyltransferase-alpha (CCT-alpha), and compared their localization with ..
  7. Naggert J, Witkowski A, Mikkelsen J, Smith S. Molecular cloning and sequencing of a cDNA encoding the thioesterase domain of the rat fatty acid synthetase. J Biol Chem. 1988;263:1146-50 pubmed
  8. Larter C, Yeh M, Haigh W, Williams J, Brown S, Bell Anderson K, et al. Hepatic free fatty acids accumulate in experimental steatohepatitis: role of adaptive pathways. J Hepatol. 2008;48:638-47 pubmed publisher
    ..in MCD-fed mice, but no consistent reduction in fatty acid synthesis genes (acetyl-CoA carboxylase and fatty acid synthase)...
  9. Du X, Cai C, Yao J, Zhou Y, Yu H, Shen W. Histone modifications in FASN modulated by sterol regulatory element-binding protein 1c and carbohydrate responsive-element binding protein under insulin stimulation are related to NAFLD. Biochem Biophys Res Commun. 2017;483:409-417 pubmed publisher
    ..1c (SREBP-1c) and carbohydrate responsive-element binding protein (ChREBP) are the major regulators of fatty acid synthase (FASN), a key enzyme of de novo fatty acid synthesis...
  10. Wu M, Singh S, Wang J, Chung C, Salituro G, Karanam B, et al. Antidiabetic and antisteatotic effects of the selective fatty acid synthase (FAS) inhibitor platensimycin in mouse models of diabetes. Proc Natl Acad Sci U S A. 2011;108:5378-83 pubmed publisher
    ..We report here that PTM is also a potent and highly selective inhibitor of mammalian fatty acid synthase. In contrast to two agents, C75 and cerulenin, that are widely used as inhibitors of mammalian fatty acid ..
  11. Witkowski A, Naggert J, Mikkelsen J, Smith S. Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase. Eur J Biochem. 1987;165:601-6 pubmed
    ..These findings lend support to the hypothesis that the polyfunctional fatty acid synthetase probably arose by a complex evolutionary process involving fusion of genes coding for seven individual enzymes. ..
  12. Amy C, Williams Ahlf B, Naggert J, Smith S. Intron-exon organization of the gene for the multifunctional animal fatty acid synthase. Proc Natl Acad Sci U S A. 1992;89:1105-8 pubmed
    The complete intron-exon organization of the gene encoding a multifunctional mammalian fatty acid synthase has been elucidated, and specific exons have been assigned to coding sequences for the component domains of the protein...
  13. Lodhi I, Wei X, Yin L, Feng C, Adak S, Abou Ezzi G, et al. Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability. Cell Metab. 2015;21:51-64 pubmed publisher
    b>Fatty acid synthase (FAS) is altered in metabolic disorders and cancer. Conventional FAS null mice die in utero, so effects of whole-body inhibition of lipogenesis following development are unknown...
  14. Nowacka Woszuk J, Madeja Z, Chmurzynska A. Prenatal caloric restriction alters lipid metabolism but not hepatic Fasn gene expression and methylation profiles in rats. BMC Genet. 2017;18:78 pubmed publisher
    ..In this study, we have applied a calorie-restricted diet during gestation and examined its effect on hepatic Fasn mRNA and DNA methylation profiles in rats and their female progeny...
  15. Chan Y, Saad S, Simar D, Oliver B, McGrath K, Reyk D, et al. Short term exendin-4 treatment reduces markers of metabolic disorders in female offspring of obese rat dams. Int J Dev Neurosci. 2015;46:67-75 pubmed publisher
    ..inhibition of peroxisomal proliferator activated receptor gamma coactivator 1α (PGC1α), increased fatty acid synthase (FASN) expression in the liver, and reduced adipocyte triglyceride lipase (ATGL) expression...
  16. Adamson A, Suchankova G, Rufo C, Nakamura M, Teran Garcia M, Clarke S, et al. Hepatocyte nuclear factor-4alpha contributes to carbohydrate-induced transcriptional activation of hepatic fatty acid synthase. Biochem J. 2006;399:285-95 pubmed
    ..by insulin and increased glucose oxidation, and both signals are necessary for optimal induction of FAS (fatty acid synthase)...
  17. Teruel T, Hernandez R, Rial E, Martin Hidalgo A, Lorenzo M. Rosiglitazone up-regulates lipoprotein lipase, hormone-sensitive lipase and uncoupling protein-1, and down-regulates insulin-induced fatty acid synthase gene expression in brown adipocytes of Wistar rats. Diabetologia. 2005;48:1180-8 pubmed
    ..uptake; (2) hormone-sensitive lipase (hsl), which mobilises fatty acids from stored triglycerides; (3) fatty acid synthase (fas), which regulates de novo lipogenesis; and (4) the uncoupling proteins (ucp) 1 and 3, which control ..
  18. Menendez J, Lupu R. Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat Rev Cancer. 2007;7:763-77 pubmed
    There is a renewed interest in the ultimate role of fatty acid synthase (FASN)--a key lipogenic enzyme catalysing the terminal steps in the de novo biogenesis of fatty acids--in cancer pathogenesis...
  19. 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. ..
  20. Maloney C, Gosby A, Phuyal J, Denyer G, Bryson J, Caterson I. Site-specific changes in the expression of fat-partitioning genes in weanling rats exposed to a low-protein diet in utero. Obes Res. 2003;11:461-8 pubmed
    ..Expression of the genes acetyl-coenzyme A carboxylase, fatty acid synthase, and carnitine palmitoyl transferase 1 were measured in liver, quadriceps muscle, and subcutaneous white ..
  21. Najjar S, Yang Y, Fernstrom M, Lee S, Deangelis A, Rjaily G, et al. Insulin acutely decreases hepatic fatty acid synthase activity. Cell Metab. 2005;2:43-53 pubmed
    Insulin is viewed as a positive regulator of fatty acid synthesis by increasing fatty acid synthase (FAS) mRNA transcription...
  22. González R, Rodriguez Cruz M, Maldonado J, Saavedra F. Role of maternal tissue in the synthesis of polyunsaturated fatty acids in response to a lipid-deficient diet during pregnancy and lactation in rats. Gene. 2014;549:7-23 pubmed publisher
    ..Gene expression of desaturases, elongases, fatty acid synthase (Fasn) and their regulator Srebf-1c was increased in the mammary gland, liver and adipose tissue of rats ..
  23. Alberdi G, Rodriguez V, Miranda J, Macarulla M, Arias N, Andres Lacueva C, et al. Changes in white adipose tissue metabolism induced by resveratrol in rats. Nutr Metab (Lond). 2011;8:29 pubmed publisher
    ..by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry...
  24. Reed M, Schweizer M, Szafranska A, Arthur C, Nicholson T, Cox R, et al. The type I rat fatty acid synthase ACP shows structural homology and analogous biochemical properties to type II ACPs. Org Biomol Chem. 2003;1:463-71 pubmed
    While X-ray and NMR structures are now available for most components of the Type II fatty acid synthase (FAS), there are no structures for Type I FAS domains...
  25. Zhao W, Zhao C, Gao L, Feng F, Gao W, Chen Z, et al. The novel inhibitory effect of Pangdahai on fatty acid synthase. IUBMB Life. 2008;60:185-94 pubmed publisher
    Recently, animal fatty acid synthase (FASN) is reported as a potential therapeutic target for obesity and cancer. Considerable interest has been developed in searching for novel inhibitors of this enzyme...
  26. Beck K, Schreglmann R, Stathopulos I, Klein H, Hoch J, Schweizer M. The fatty acid synthase (FAS) gene and its promoter in Rattus norvegicus. DNA Seq. 1992;2:359-86 pubmed
    Screening of rat liver genomic libraries yielded 5 overlapping clones for rat fatty acid synthase (FAS)...
  27. MacDonald M, Hasan N, Dobrzyn A, Stoker S, Ntambi J, Liu X, et al. Knockdown of pyruvate carboxylase or fatty acid synthase lowers numerous lipids and glucose-stimulated insulin release in insulinoma cells. Arch Biochem Biophys. 2013;532:23-31 pubmed publisher
    ..We now show that knockdown of fatty acid synthase (FAS) mRNA and protein also inhibits glucose-stimulated insulin release in this cell line...
  28. Witkowski A, Ghosal A, Joshi A, Witkowska H, Asturias F, Smith S. Head-to-head coiled arrangement of the subunits of the animal fatty acid synthase. Chem Biol. 2004;11:1667-76 pubmed
  29. Joseph J, Odegaard M, Ronnebaum S, Burgess S, Muehlbauer J, Sherry A, et al. Normal flux through ATP-citrate lyase or fatty acid synthase is not required for glucose-stimulated insulin secretion. J Biol Chem. 2007;282:31592-600 pubmed
    ..Key enzymes involved in synthesis of fatty acids from glucose include ATP-citrate lyase (CL) and fatty acid synthase (FAS)...
  30. Clarke S, Armstrong M, Jump D. Nutritional control of rat liver fatty acid synthase and S14 mRNA abundance. J Nutr. 1990;120:218-24 pubmed
    The objective of this research was to evaluate the change in abundance of S14 and fatty acid synthase (FAS) mRNAs under a variety of nutritional conditions to evaluate the hypothesis that the regulation of the S14 gene is similar to that ..
  31. Brignole E, Smith S, Asturias F. Conformational flexibility of metazoan fatty acid synthase enables catalysis. Nat Struct Mol Biol. 2009;16:190-7 pubmed publisher
    The metazoan cytosolic fatty acid synthase (FAS) contains all of the enzymes required for de novo fatty acid biosynthesis covalently linked around two reaction chambers...
  32. Suburu J, Shi L, Wu J, Wang S, Samuel M, Thomas M, et al. Fatty acid synthase is required for mammary gland development and milk production during lactation. Am J Physiol Endocrinol Metab. 2014;306:E1132-43 pubmed publisher
    ..The committed enzyme to perform this function is fatty acid synthase (FASN)...
  33. Chirala S, Jayakumar A, Gu Z, Wakil S. Human fatty acid synthase: role of interdomain in the formation of catalytically active synthase dimer. Proc Natl Acad Sci U S A. 2001;98:3104-8 pubmed
    ..We show here that the fatty acid synthase activity could not be reconstituted when the ID sequences present in the two recombinant halves are deleted,..
  34. Teran Garcia M, Adamson A, Yu G, Rufo C, Suchankova G, Dreesen T, et al. Polyunsaturated fatty acid suppression of fatty acid synthase (FASN): evidence for dietary modulation of NF-Y binding to the Fasn promoter by SREBP-1c. Biochem J. 2007;402:591-600 pubmed
    ..Suppression of Fasn (fatty acid synthase) transcription involves two PUFA-responsive regions, but the majority of PUFA sensitivity maps to a region ..
  35. Menendez J, Vazquez Martin A, Ortega F, Fernandez Real J. Fatty acid synthase: association with insulin resistance, type 2 diabetes, and cancer. Clin Chem. 2009;55:425-38 pubmed publisher
    An emerging paradigm supports the notion that deregulation of fatty acid synthase (FASN)-catalyzed de novo FA biogenesis could play a central role in the pathogenesis of metabolic diseases sharing the hallmark of insulin-resistance...
  36. Rendina A, Cheng D. Characterization of the inactivation of rat fatty acid synthase by C75: inhibition of partial reactions and protection by substrates. Biochem J. 2005;388:895-903 pubmed
    C75, a synthetic inhibitor of FAS (fatty acid synthase), has both anti-tumour and anti-obesity properties. In this study we provide a detailed kinetic characterization of the mechanism of in vitro inhibition of rat liver FAS...
  37. Moon Y, Latasa M, Griffin M, Sul H. Suppression of fatty acid synthase promoter by polyunsaturated fatty acids. J Lipid Res. 2002;43:691-8 pubmed
    Dietary polyunsaturated fat is known to suppress expression of fatty acid synthase (FAS), a central enzyme in de novo lipogenesis...
  38. Amy C, Witkowski A, Naggert J, Williams B, Randhawa Z, Smith S. Molecular cloning and sequencing of cDNAs encoding the entire rat fatty acid synthase. Proc Natl Acad Sci U S A. 1989;86:3114-8 pubmed
    Overlapping cloned cDNAs representing the entire sequence of the rat fatty acid synthase mRNA have been isolated from a cDNA library and sequenced...
  39. Huong D, Ide T. Dietary lipoic acid-dependent changes in the activity and mRNA levels of hepatic lipogenic enzymes in rats. Br J Nutr. 2008;100:79-87 pubmed
    ..Lipoic acid dose-dependently decreased the activity and mRNA levels of fatty acid synthase, ATP-citrate lyase, glucose 6-phosphate dehydrogenase, malic enzyme and pyruvate kinase in the liver ..