Cloning and characterization of a mammalian fatty acyl-CoA elongase as a lipogenic enzyme regulated by SREBPs

Abstract

The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full-length cDNA indicate that the encoded protein, designated fatty acyl-CoA elongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated- and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression.These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase. The mammalian enzyme involved in the final elongation of de novo fatty acid biosynthesis following the building of fatty acids to 16 carbons by fatty acid synthase has yet to be identified. In the process of searching for genes activated by sterol regulatory element-binding protein 1 (SREBP-1) by using DNA microarray, we identified and characterized a murine cDNA clone that is highly similar to a fatty acyl-CoA elongase gene family such as Cig30, Sscs, and yeast ELOs. Studies on the cells overexpressing the full-length cDNA indicate that the encoded protein, designated fatty acyl-CoA elongase (FACE), has a FACE activity specific for long-chains; C12-C16 saturated- and monosaturated-fatty acids. Hepatic expression of this identified gene was consistently activated in the livers of transgenic mice overexpressing nuclear SREBP-1a, -1c, or -2. FACE mRNA levels are markedly induced in a refed state after fasting in the liver and adipose tissue. This refeeding response is significantly reduced in SREBP-1 deficient mice. Dietary PUFAs caused a profound suppression of this gene expression, which could be restored by SREBP-1c overexpression. Hepatic FACE expression was also highly up-regulated in leptin-deficient ob/ob mice. Hepatic FACE mRNA was markedly increased by administration of a pharmacological agonist of liver X-activated receptor (LXR), a dominant activator for SREBP-1c expression. These data indicated that this elongase is a new member of mammalian lipogenic enzymes regulated by SREBP-1, playing an important role in de novo synthesis of long-chain saturated and monosaturated fatty acids in conjunction with fatty acid synthase and stearoyl-CoA desaturase. Biosynthesis of fatty acids is the major function part of lipogenesis in its role as an energy storage system. Fatty acids with lengths of 16–18 carbon atoms, constituting the majority of total fatty acids in the cells, are major products of de novo synthesis in most mammalian tissues. These long chain fatty acids play an important role in cellular biological functions, including: energy metabolism, membrane fluidity, and others. There appear to be several distinct metabolic pathways that produce long chain fatty acids. Cytoplasmic fatty acid synthase (FAS) plays a major role in the de novo synthesis of fatty acids. However, the elongation of fatty acids by this enzyme terminates at palmitic acid (C16:0). The end product of mammalian lipogenesis is usually oleic acid (C18:1n-9) or vaccenic acid (C18:1n-7) (1Nelson G.J. Kelley D.S. Hunt J.E. Effect of nutritional status on the fatty acid composition of rat liver and cultured hepatocytes..Lipids. 1986; 21: 454-459Crossref PubMed Scopus (29) Google Scholar, 2Ntambi J.M. Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol..J. Lipid Res. 1999; 40: 1549-1558Abstract Full Text Full Text PDF PubMed Google Scholar). Mammals have long been thought to possess a membrane bound enzyme that elongates and/or desaturates saturated fatty acyl-CoAs produced by FAS or derived from dietary resources (3Cinti D.L. Cook L. Nagi M.N. Suneja S.K. The fatty acid chain elongation system of mammalian endoplasmic reticulum..Prog. Lipid Res. 1992; 31: 1-51Crossref PubMed Scopus (192) Google Scholar). Stearoyl-CoA desaturase (SCD) has been shown to be committed to the desaturation; however, the gene catalyzing for the C2 elongation of the C16:0 and C16:1 has never been identified. To date, several enzymes involved in the elongation of long-chain fatty acids in non-mammalian cells have been identified. One such family consists of the yeast ELO genes. The yeast ELO1 gene is involved in the elongation of C14:0 to C16:0 (4Toke D.A. Martin C.E. Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae..J. Biol. Chem. 1996; 271: 18413-18422Abstract Full Text Full Text PDF PubMed Scopus (158) Google Scholar). The ELO2 and ELO3 genes were identified based on the homology to the ELO1 gene (5Oh C.S. Toke D.A. Mandala S. Martin C.E. ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation..J. Biol. Chem. 1997; 272: 17376-17384Abstract Full Text Full Text PDF PubMed Scopus (395) Google Scholar). ELO2 protein is involved in the elongation of saturated and monounsaturated fatty acids up to 24 carbons in length, while ELO3 elongates a broader group of saturated and monounsaturated fatty acids, and is essential for the conversion of C24:0 into C26:0 (5Oh C.S. Toke D.A. Mandala S. Martin C.E. ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation..J. Biol. Chem. 1997; 272: 17376-17384Abstract Full Text Full Text PDF PubMed Scopus (395) Google Scholar). Another known elongase family, Cig30, which was originally identified as a cold-induced gene in brown fat, is the first mouse fatty acid elongase identified (6Tvrdik P. Asadi A. Kozak L.P. Nedergaard J. Cannon B. Jacobsson A. Cig30, a mouse member of a novel membrane protein gene family, is involved in the recruitment of brown adipose tissue..J. Biol. Chem. 1997; 272: 31738-31746Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar). Ssc1 and Ssc2 were cloned based on the homology to Cig30 (7Tvrdik P. Westerberg R. Silve S. Asadi A. Jakobsson A. Cannon B. Loison G. Jacobsson A. Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids..J. Cell Biol. 2000; 149: 707-717Crossref PubMed Scopus (182) Google Scholar). Complementation studies in yeast mutants indicated that Cig30 and SSC1 are functionally orthologous to ELO2 and ELO3, respectively. The specific activity of Ssc2 has not been identified. Elovl4, a retinal photoreceptor-specific gene, plays a role in the elongation of very long chain fatty acids and has been reported to be a causative gene for inherited macular degeneration (8Zhang K. Kniazeva M. Han M. Li W. Yu Z. Yang Z. Li Y. Metzker M.L. Allikmets R. Zack D.J. Kakuk L.E. Lagali P.S. Wong P.W. MacDonald I.M. Sieving P.A. Figueroa D.J. Austin C.P. Gould R.J. Ayyagari R. Petrukhin K. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy..Nat. Genet. 2001; 27: 89-93Crossref PubMed Scopus (375) Google Scholar). HELO1, as a member of HELO family cloned by homology to ELO2, is involved in the elongation of PUFAs and monounsaturated fatty acids, whereas the specific activity of HELO2 has not been not identified (9Leonard A.E. Bobik E.G. Dorado J. Kroeger P.E. Chuang L.T. Thurmond J.M. Parker-Barnes J.M. Das T. Huang Y.S. Mukerji P. Cloning of a human cDNA encoding a novel enzyme involved in the elongation of long-chain polyunsaturated fatty acids..Biochem. J. 2000; 350: 765-770Crossref PubMed Scopus (0) Google Scholar). These elongase could consist of a family that share a common structure of at least five membrane-spanning regions and a single histidine-box motif. Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that belong to the basic helix-loop-helix leucine zipper family (10Brown M.S. Goldstein A that the of cells, and 1999; PubMed Scopus Google Scholar, M.S. Goldstein The of by of a membrane-bound transcription 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M.S. J. Goldstein a from to 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). have been as a for biosynthesis of and fatty acids. To activity on have to in a with a protein, that for a a for of cellular There are of that have been and known as and A. J. Goldstein M.S. SREBP-1, a zipper protein that transcription of the receptor Full Text PDF PubMed Scopus Google Scholar, P. a novel helix-loop-helix transcription associated with and Biol. PubMed Scopus Google Scholar, J. M.S. Goldstein a zipper protein that transcription by to a sterol regulatory PubMed Scopus Google Scholar). which are involved in energy storage synthesis of fatty acids and are regulated at the metabolic in studies that SREBP-1c plays a role in the dietary of most lipogenic whereas is involved in the transcription of These studies of the of the or of SREBP-1 on lipogenic gene expression M. Goldstein of and fatty acids liver in transgenic mice 1996; PubMed Scopus Google Scholar, M. A. J. Y. Y. K. K. T. S. Sterol regulatory element-binding as a transcription for nutritional of lipogenic enzyme Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M.S. Goldstein of synthesis in to fatty acid synthesis in liver and adipose of transgenic mice sterol regulatory element-binding PubMed Google as as of SREBP-1c protein in mice after dietary such as on and Y. Regulation of sterol regulatory proteins in livers of and refed PubMed Scopus Google Scholar, A. M. Y. Y. K. J. K. T. R. S. A role of sterol regulatory element-binding in the of lipogenic gene expression by polyunsaturated fatty Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Sterol regulatory expression is by dietary polyunsaturated fatty acids. A for the suppression of lipogenic genes by polyunsaturated Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. sterol regulatory element-binding protein 1 (SREBP-1) by of SREBP-1c mRNA in mouse A for of lipogenic enzyme Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). on the of SREBP-1c have the to be at the mRNA that the expression of the SREBP-1c gene is regulated by two an and liver X-activated acid receptor receptor M. T. Y. Y. K. K. T. R. S. S. of the mouse sterol regulatory element-binding protein Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, G. J. Y. J.M. B. M.S. Goldstein D.J. Regulation of mouse sterol regulatory element-binding gene by and 2000; PubMed Scopus Google Scholar, T. M. T. Y. Y. K. J. K. T. S. S. of liver receptor as an activator of the sterol regulatory element-binding protein gene Biol. 2001; 21: PubMed Scopus Google Scholar, A. Li L. S. S. M. D.J. B. Role of in of 2000; PubMed Scopus Google Scholar). In the of we cloned a mammalian fatty acid designated fatty acyl-CoA elongase data that the enzyme activity of this clone the in the conversion of to fatty acids. In the nutritional of this FACE expression is with its as a lipogenic fatty acids from enzymes from from and from were DNA was with the and DNA expression cDNA of transgenic liver M. Goldstein of and fatty acids liver in transgenic mice 1996; PubMed Scopus Google was as for of a cDNA of SREBP-1 deficient mouse adipose that was from livers of transgenic mice T. M. T. Y. Y. K. J. K. T. S. S. of liver receptor as an activator of the sterol regulatory element-binding protein gene Biol. 2001; 21: PubMed Scopus Google Scholar). a DNA system using of transgenic and mice we identified an clone that was activated in transgenic liver as with this a DNA was and in the of an transgenic mouse liver cDNA by were however, the were the of the To the of the the was was using from the liver of a transgenic mouse and was for cDNA synthesis and with the The cDNA was to of mouse and mouse The a of mouse which a single of with to Cig30, known mouse fatty acid The elongase gene was designated and were based on the FACE and to the FACE cDNA from transgenic mouse liver The product was into and The FACE was from this by and using DNA and into of expression cells were at in an of in and with on the mouse FACE expression or the was into cells using to the cells were with for 24 The from the cells were as with of the protein by an membrane Biol. Chem. Full Text PDF PubMed Google Scholar). after the cells were with and in of The cells were and in of and The was for at The was in 1 of and the was at for at The were and at for at from this was at for at The were in of and for fatty acid elongation fatty acid elongation activity was by the of into acyl-CoAs as M. R. M. T. M. of rat fatty acid chain elongation and by with J. PubMed Scopus Google with The protein and of of at the was by the of of and for at The was by of of in and at for the were and with of fatty acids were from the with 1 of The were and after of of the was were in mice were in a with a and to and fatty acid or mice were from and to the for 1 to group of was a the indicated fatty acids and for SREBP-1a, and -1c, and transgenic mice M. Goldstein of and fatty acids liver in transgenic mice 1996; PubMed Scopus Google Scholar, M.S. Goldstein of synthesis in to fatty acid synthesis in liver and adipose of transgenic mice sterol regulatory element-binding PubMed Google Scholar, M.S. Goldstein of sterol regulatory protein is in livers of transgenic mice and in cultured 1997; PubMed Scopus Google and of transgenic were on a for to the expression, and were for fasting and refeeding SREBP-1 deficient J. Goldstein M.S. levels of and synthesis in livers of mice for a of the SREBP-1 1997; PubMed Scopus Google and mice were for 24 and a for mice on a were from mice were to deficient ob/ob mice and mice. ob/ob and mice were in the following a was from mouse adipose and using were on a and to a membrane The were with using the DNA The cDNA for mouse FACE was by the cloned cDNA with The cDNA for mouse SREBP-1 and were as M. A. J. Y. Y. K. K. T. S. Sterol regulatory element-binding as a transcription for nutritional of lipogenic enzyme Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The were with the in at and in at The were by of the to with DNA identified an clone expression was increased in the livers of transgenic mice as with mice. this clone as a we the full-length cDNA by an transgenic liver cDNA by shown in of this clone that a protein of acid with a of and very basic of a human of mouse FACE after searching The acid that and in mouse and human by the J. A for the of a Biol. PubMed Scopus Google that this protein five for of the elongase family in enzymes proteins J. are essential in a stearoyl-CoA and are in and Scopus Google was regions and at acid and could function to from or a in an The of the FACE a in that the protein is in the endoplasmic membrane T. P.A. of a for of proteins in the endoplasmic J. PubMed Scopus Google Scholar). The acid of mouse FACE a to Cig30 Ssc1 Ssc2 and of which are known to be involved in the elongation of fatty acids by two carbon atoms, and of this protein family acid of mouse FACE acid in the are indicated the protein The of enzymes a is This cDNA clone is highly to a mammalian fatty acid and is designated the FACE cDNA was in cells with fatty acids, of the cellular fatty acids a that of FACE caused a in the of acid and oleic acid a in palmitic acid and acid in the cells as with cells not These data that the cells with FACE were of from that FACE is involved in the elongation of C16:0 and that FACE have an elongase for To that FACE plays a role in the conversion of C16:0 to we in fatty acid elongation fatty acid elongation activity was by the of into acyl-CoA of saturated and fatty acids with chain to stearoyl-CoA and with cells that been with the of the FACE cDNA in two in elongase activity and stearoyl-CoA and were as a were in the elongation These data that FACE elongase activity specific to saturated and monounsaturated fatty acids. of FACE was in as by the dominant of mouse FACE is in mouse also a that is in to the of two in the The expression was in and lipogenesis and are expression was in and whereas the dominant in is To of FACE expression and to the of nuclear was on liver from nuclear SREBP-1a, -1c, and transgenic and mice. shown in mRNA levels of FACE were increased by of nuclear SREBP-1a, and in this of The FACE was from livers of in transgenic This was also regulated in the as the major with the that the are to The data indicate that of the expression of FACE gene, with the the most of FACE mRNA levels was in and SREBP-1 deficient mice. These mice were and refed a shown in the mRNA levels of FACE were in livers of mice and markedly activated by refeeding in the nutritional of FACE as a lipogenic The mRNA of FACE in the mice was and similar to of mice. However, the mice a of FACE refeeding with mice. These data that the expression of FACE is at least the of the In to adipose is in which lipogenic enzymes are thought to to at the transcription shown in in mRNA levels of FACE from adipose of mice were similar to in the adipose of FACE in and refed These data that FACE mRNA in lipogenic are regulated in a lipogenic and are regulated by SREBP-1, expression is also involved in FACE expression. dietary studies indicate that activity and expression of lipogenic enzymes are by in PUFAs such as or A. M. Y. Y. K. J. K. T. R. S. A role of sterol regulatory element-binding in the of lipogenic gene expression by polyunsaturated fatty Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Sterol regulatory expression is by dietary polyunsaturated fatty acids. A for the suppression of lipogenic genes by polyunsaturated Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. sterol regulatory element-binding protein 1 (SREBP-1) by of SREBP-1c mRNA in mouse A for of lipogenic enzyme Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). to mouse FACE expression levels in mice with the of fatty acids for that and not the expression of However, the was with or acid the expression of FACE was and the was with in and acid This to to the of suppression for lipogenic enzymes that are regulated by SREBP-1 A. M. Y. Y. K. J. K. T. R. S. A role of sterol regulatory element-binding in the of lipogenic gene expression by polyunsaturated fatty Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). To the suppression of FACE was to the in SREBP-1, we also suppression of FACE expression in SREBP-1c transgenic mice This of transgenic mice similar of nuclear SREBP-1c protein, derived from the to the of nuclear SREBP-1c in the livers from refed mice A. M. Y. Y. K. J. K. T. R. S. A role of sterol regulatory element-binding in the of lipogenic gene expression by polyunsaturated fatty Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The of nuclear SREBP-1c suppression of FACE mRNA These data that SREBP-1c is involved in FACE expression in a deficient mice are an murine for and studies indicate that the mRNA of SREBP-1 and genes involved in fatty acid biosynthesis were significantly in livers from ob/ob mice with in Y. levels of nuclear SREBP-1c associated with fatty livers in two mouse of Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, A. P. J.M. of gene expression in adipose 2000; Google Scholar). FACE mRNA levels in livers and by shown in mRNA levels of FACE and SREBP-1 from ob/ob mice were with In the mRNA levels of FACE and SREBP-1 not a in adipose from ob/ob and mice These data are with the lipogenic enzymes are regulated in ob/ob mice FACE by The and have been shown to SREBP-1c and expression of its lipogenic enzyme genes G. J. Y. J.M. B. M.S. Goldstein D.J. Regulation of mouse sterol regulatory element-binding gene by and 2000; PubMed Scopus Google Scholar, T. M. T. Y. Y. K. J. K. T. S. S. of liver receptor as an activator of the sterol regulatory element-binding protein gene Biol. 2001; 21: PubMed Scopus Google Scholar, A. Li L. S. S. M. D.J. B. Role of in of 2000; PubMed Scopus Google Scholar). shown in administration of a pharmacological agonist A. Li L. S. S. M. D.J. B. Role of in of 2000; PubMed Scopus Google significantly increased FACE mRNA whereas the agonist and the agonist These data that SREBP-1c is involved in the expression of The FACE expression was not highly induced by the in adipose the is In the we have the and characterization of a cDNA that to a mammalian fatty acid which we have FACE cDNA acid and five a and for of fatty acid elongase family (6Tvrdik P. Asadi A. Kozak L.P. Nedergaard J. Cannon B. Jacobsson A. Cig30, a mouse member of a novel membrane protein gene family, is involved in the recruitment of brown adipose tissue..J. Biol. Chem. 1997; 272: 31738-31746Abstract Full Text Full Text PDF PubMed Scopus (88) Google Scholar, P. Westerberg R. Silve S. Asadi A. Jakobsson A. Cannon B. Loison G. Jacobsson A. Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids..J. Cell Biol. 2000; 149: 707-717Crossref PubMed Scopus (182) Google Scholar, K. Kniazeva M. Han M. Li W. Yu Z. Yang Z. Li Y. Metzker M.L. Allikmets R. Zack D.J. Kakuk L.E. Lagali P.S. Wong P.W. MacDonald I.M. Sieving P.A. Figueroa D.J. Austin C.P. Gould R.J. Ayyagari R. Petrukhin K. A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy..Nat. Genet. 2001; 27: 89-93Crossref PubMed Scopus (375) Google Scholar). in of the enzyme for this elongation could be to its studies that FACE has specific activity for the elongation of fatty acids C16:0 and a that FAS be in the cellular fatty acid synthesis that C16:0 produced by fatty acid synthase in the is to and are involved to produce the final as in the that is a for and In the process of this of the gene from the similar and characterization of the enzyme activity was reported S. of a mammalian long chain fatty elongase regulated by sterol regulatory element-binding Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). was shown to have elongase activity for fatty acids. that FACE also has an elongase activity for conversion of to was reported consistently that as as is increased in the fatty of liver of in a refed state (1Nelson G.J. Kelley D.S. Hunt J.E. Effect of nutritional status on the fatty acid composition of rat liver and cultured hepatocytes..Lipids. 1986; 21: 454-459Crossref PubMed Scopus (29) Google Scholar). The FACE cDNA an long of which is similar to J.M. R.J. gene expression in of a gene encoding stearoyl-CoA Biol. Chem. Full Text PDF PubMed Google Scholar, L. L. S. K. stearoyl-CoA from a single gene by of J. 1999; PubMed Scopus Google Scholar). The of and FACE in protein and gene and the of proteins that genes could be derived from a common The role of such a long is however, FACE to such as and a response that in to by several of mRNA are in the of the These play in the of several in response to factors R.J. Cytoplasmic of mRNA the of the Full Text PDF PubMed Scopus Google Scholar). The as a to the of this gene and studies on in of FACE in mice that expression of FACE is by SREBP-1 as lipogenic is the major of de novo synthesis of fatty acids in mammalian the major fatty acid of livers of transgenic mice was that the of this Y. sterol regulatory element-binding proteins genes for the of fatty acid biosynthesis in transgenic mouse Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). FAS and are is that FACE is also regulated by mouse studies that of FACE expression. FACE could also be by in to lipogenic by To FACE as an gene, on the FACE gene is the of and in the that FACE is a of S. of a mammalian long chain fatty elongase regulated by sterol regulatory element-binding Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). FACE mRNA in lipogenic of SREBP-1 mice could be to the of J. Goldstein M.S. levels of and synthesis in livers of mice for a of the SREBP-1 1997; PubMed Scopus Google or FACE is in could play a role in a cellular function in to lipogenesis as an energy storage system. that FACE is a new member of the lipogenic enzyme family, based its fatty elongation and lipogenic in such as at refeeding and the role of FACE in lipogenesis known enzymes have been reported to the activity as in this However, the of this gene in lipogenesis as an energy storage system or in cellular of of the FACE gene such as characterization of gene mice. of the resources by that human and FACE is to and mouse FACE is to is that the of FACE gene is very to a that has been reported to be to human by a J. M. S. J. T. A for to human a on 2001; PubMed Scopus Google Scholar). was reported that elongase activity by in the is significantly related to in D.A. S. membrane composition is related to and PubMed Scopus Google that FACE could be related to human studies of FACE to human or The S. and L. Goldstein for for the This was by the of Studies in of the for and acyl-CoA protein acyl-CoA fatty acyl-CoA elongase fatty acid synthase liver X-activated receptor acid receptor stearoyl-CoA desaturase sterol regulatory element-binding protein adipose