Sequential Regulation of Diacylglycerol Acyltransferase 2 Expression by CAAT/Enhancer-binding Protein β (C/EBPβ) and C/EBPα during Adipogenesis

Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triacylglycerol (TG) synthesis. Despite the existence of an alternative acyltransferase (DGAT1), mice lacking DGAT2 have a severe deficiency of TG in adipose tissue, indicating a nonredundant role for this enzyme in adipocyte TG synthesis. We have studied the regulation of DGAT2 expression during adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells the temporal pattern of DGAT2 expression closely mimicked that of genes whose expression is regulated by CAAT/enhancer-binding protein β (C/EBPβ). Inhibition of C/EBPβ expression in differentiating preadipocytes reduced DGAT2 expression, and electrophoretic mobility shift assay and chromatin immunoprecipitation experiments identified a promoter element in the DGAT2 gene that is likely to mediate this effect. The importance of C/EBPβ in adipocyte expression of DGAT2 was confirmed by the finding of reduced DGAT2 expression in the adipose tissue of C/EBPβ-null animals. However, DGAT2 expression is maintained at high levels during the later stages of adipogenesis, when C/EBPβ levels decline. We show that, at these later stages of differentiation, C/EBPα is capable of substituting for C/EBPβ at the same promoter element. These observations provide novel insight into the transcriptional regulation of DGAT2 expression. Moreover, they further refine the complex and serial roles of the C/EBP family of transcription factors in inducing and maintaining the metabolic properties of mature adipocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step of triacylglycerol (TG) synthesis. Despite the existence of an alternative acyltransferase (DGAT1), mice lacking DGAT2 have a severe deficiency of TG in adipose tissue, indicating a nonredundant role for this enzyme in adipocyte TG synthesis. We have studied the regulation of DGAT2 expression during adipogenesis. In both isolated murine preadipocytes and 3T3-L1 cells the temporal pattern of DGAT2 expression closely mimicked that of genes whose expression is regulated by CAAT/enhancer-binding protein β (C/EBPβ). Inhibition of C/EBPβ expression in differentiating preadipocytes reduced DGAT2 expression, and electrophoretic mobility shift assay and chromatin immunoprecipitation experiments identified a promoter element in the DGAT2 gene that is likely to mediate this effect. The importance of C/EBPβ in adipocyte expression of DGAT2 was confirmed by the finding of reduced DGAT2 expression in the adipose tissue of C/EBPβ-null animals. However, DGAT2 expression is maintained at high levels during the later stages of adipogenesis, when C/EBPβ levels decline. We show that, at these later stages of differentiation, C/EBPα is capable of substituting for C/EBPβ at the same promoter element. These observations provide novel insight into the transcriptional regulation of DGAT2 expression. Moreover, they further refine the complex and serial roles of the C/EBP family of transcription factors in inducing and maintaining the metabolic properties of mature adipocytes. The increased adipose tissue mass of obesity results from a combination of increased lipid storage in existing adipocytes and the generation of new adipocytes from precursors residing within the adipose tissue (1Camp H.S. Ren D. Leff T. Trends Mol. Med. 2002; 8: 442-447Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar). The induction of genes responsible for the formation of triacylglycerol (TG) 3The abbreviations used are: TG, triacylglycerol; DGAT, diacylglycerol acyltransferase; C/EBP, CAAT/enhancer-binding protein; PPAR, peroxisome proliferator-activated receptor; PEPCK, phosphoenolpyruvate carboxykinase; LIP, liver inhibitory protein; ETO, eight-twenty one/MTG8; siRNA, small interference RNA; ChIP, chromatin immunoprecipitation. within developing or pre-existing adipocytes is therefore likely to make an important contribution to the enlargement of adipose mass. In contrast, pathologically decreased lipid accumulation or impaired adipogenesis in lipodystrophic subjects has deleterious metabolic consequences superficially like those seen in obesity, including insulin resistance and dyslipidemia, with attendant increases in cardiovascular disease. Thus good metabolic control is likely to require the body to restrain adipose tissue mass while still maintaining the capacity to respond accurately to substrate availability. In this way, when necessary, lipids can be partitioned appropriately into adipose tissue and away from other insulin-sensitive tissues where they may have detrimental effects. That mutations of AGPAT2, a key enzyme in TG synthesis, can cause near total lipodystrophy demonstrates the importance of this pathway in such diseases of adipose development and function (2Agarwal A.K. Arioglu E. De Almeida S. Akkoc N. Taylor S.I. Bowcock A.M. Barnes R.I. Garg A. Nat. Genet. 2002; 31: 21-23Crossref PubMed Scopus (433) Google Scholar, 3Magre J. Delepine M. Van Maldergem L. Robert J.J. Maassen J.A. Meier M. Panz V.R. Kim C.A. Tubiana-Rufi N. Czernichow P. Seemanova E. Buchanan C.R. Lacombe D. Vigouroux C. Lascols O. Kahn C.R. Capeau J. Lathrop M. Diabetes. 2003; 52: 1573-1578Crossref PubMed Scopus (75) Google Scholar). Rational therapeutic strategies for both obesity and lipodystrophy will require a detailed knowledge of the regulatory pathways required for the formation of an appropriate mass of metabolically active adipocytes, capable of tightly controlling lipid synthesis and storage. The enzyme diacylglycerol acyltransferase (DGAT) catalyzes the final step of mammalian TG synthesis, and two isoforms, DGAT1 and DGAT2, exist, encoded by different genes. DGAT1 knock-out mice have been shown to be resistant to high fat diet-induced obesity due to increased metabolic rate with increased physical activity (4Smith S.J. Cases S. Jensen D.R. Chen H.C. Sande E. Tow B. Sanan D.A. Raber J. Eckel R.H. Farese Jr., R.V. Nat. Genet. 2000; 25: 87-90Crossref PubMed Scopus (754) Google Scholar, 5Buhman K.K. Smith S.J. Stone S.J. Repa J.J. Wong J.S. Knapp Jr., F.F. Burri B.J. Hamilton R.L. Abumrad N.A. Farese Jr., R.V. J. Biol. Chem. 2002; 277: 25474-25479Abstract Full Text Full Text PDF PubMed Scopus (200) Google Scholar, 6Chen H.C. Smith S.J. Ladha Z. Jensen D.R. Ferreira L.D. Pulawa L.K. McGuire J.G. Pitas R.E. Eckel R.H. Farese Jr., R.V. J. Clin. Invest. 2002; 109: 1049-1055Crossref PubMed Scopus (289) Google Scholar). Mice lacking DGAT2, however, show a more dramatic phenotype, with severe lipopenia and early postnatal death due to a lack of substrates for energy metabolism and defects of skin permeability (7Stone S.J. Myers H.M. Watkins S.M. Brown B.E. Feingold K.R. Elias P.M. Farese Jr., R.V. J. Biol. Chem. 2004; 279: 11767-11776Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar). Thus, DGAT2 has a key role in TG synthesis and, in addition, is highly expressed in adipocytes. However, the molecular mechanisms controlling its expression in adipose tissue have not been defined to date. The transcriptional control of gene expression during adipogenesis involves the complex interplay of a multitude of transcription factors whose temporal expression must be precisely coordinated (8Rangwala S.M. Lazar M.A. Annu. Rev. Nutr. 2000; 20: 535-559Crossref PubMed Scopus (272) Google Scholar, 9Rosen E.D. Walkey C.J. Puigserver P. Spiegelman B.M. Genes Dev. 2000; 14: 1293-1307Crossref PubMed Google Scholar, 10MacDougald O.A. Mandrup S. Trends Endocrinol. Metab. 2002; 13: 5-11Abstract Full Text Full Text PDF PubMed Scopus (309) Google Scholar). Several factors have been shown to play central roles in this transcriptional cascade. The induction of C/EBPβ and C/EBPδ occurs rapidly following the initiation of adipogenesis, and these factors, modulated by a plethora of cofactors, induce the expression of a second wave of genes, including the so-called “master regulators” of adipogenesis, C/EBPα and PPARγ. The targets of these transcription factors include the genes encoding many genes of the mature lipogenic and insulin-sensitive adipocyte such as aP2, PEPCK, aquaporin 7, lipoprotein lipase, adiponectin, and Glut4 (8Rangwala S.M. Lazar M.A. Annu. Rev. Nutr. 2000; 20: 535-559Crossref PubMed Scopus (272) Google Scholar, 11Rosen E.D. Spiegelman B.M. Annu. Rev. Cell Dev. Biol. 2000; 16: 145-171Crossref PubMed Scopus (1071) Google Scholar, 12Semple R.K. Chatterjee V.K. O'Rahilly S. J. Clin. Invest. 2006; 116: 581-589Crossref PubMed Scopus (695) Google Scholar). Thus the C/EBP family of transcription factors has a critical role in adipogenesis, and studies of both the loss and gain of function in vitro and in vivo have demonstrated the importance of their activity in adipocyte development and lipid accumulation. Ablation of C/EBPα in mice leads to a loss of white adipose tissue and impaired adipogenesis in culture, whereas the expression of C/EBPα in fibroblasts and preadipocytes facilitates adipogenesis (13Lin F.T. Lane M.D. Genes Dev. 1992; 6: 533-544Crossref PubMed Scopus (283) Google Scholar, 14Freytag S.O. Paielli D.L. Gilbert J.D. Genes Dev. 1994; 8: 1654-1663Crossref PubMed Scopus (400) Google Scholar, 15Lin F.T. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar, A. M.D. Taylor D.R. PubMed Scopus Google Scholar, M.D. F.T. O.A. M. J. Metab. 20: Google Scholar, T. D. B. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). the of the rapidly C/EBPβ and C/EBPδ have demonstrated that loss of function of or both of these factors can to decreased adipose mass in mice and decreased adipogenesis in T. N. T. S. J. 16: PubMed Scopus Google Scholar, Chen Mol. Cell Biol. 2000; 20: PubMed Scopus Google Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S. T. S. J. Cell Sci. 2002; PubMed Scopus Google Scholar). C/EBPβ and C/EBPδ to have and C/EBPβ to have the adipocyte development and lipid accumulation (13Lin F.T. Lane M.D. Genes Dev. 1992; 6: 533-544Crossref PubMed Scopus (283) Google Scholar, 14Freytag S.O. Paielli D.L. Gilbert J.D. Genes Dev. 1994; 8: 1654-1663Crossref PubMed Scopus (400) Google Scholar, 15Lin F.T. Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 1994; 91: PubMed Scopus Google Scholar, A. M.D. Taylor D.R. PubMed Scopus Google Scholar, M.D. F.T. O.A. M. J. Metab. 20: Google Scholar, T. D. B. Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar). the control of DGAT2 expression during adipogenesis and, for the a transcriptional for the regulation of its expression, a key role for the C/EBP family of transcription and culture, and as S. M. M. O'Rahilly S. J. Biol. Chem. 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C/EBPβ or C/EBPα from 3T3-L1 preadipocytes at a cells in the 2 of and of with cells for in the of was with 3T3-L1 for the induction of and was from an tissue was isolated from C/EBPβ-null mice or their as S. C. C. M. Ren J. J. Clin. Invest. PubMed Scopus Google Scholar). by the and adipose tissue with was isolated to the in of and was by The of was by was used to the and for to DGAT2, and expression. The to assay C/EBPα was from was murine and The was used in in of and and, where of used in combination with or in for an to the The of by and to or 3T3-L1 preadipocytes for with and at at The was to protein a and protein electrophoretic mobility shift assay was a electrophoretic mobility shift assay The by with their with The as C/EBPα promoter C/EBP DGAT2 C/EBP The was at for in a final of of of and of The by in 2 at at for 2 in to by with at for to the by and by a the more in the 2 of or in the for the was preadipocytes in for as The and protein in with at for chromatin was a assay The was for at The with of or protein The from by with at for The was further by a The was in of of was used to assay the of with the including the and to the from to those from by in by as J.J. R.K. M. C. C. C.J. S. D. M. A. O'Rahilly S. Mol. Cell Biol. 2004; PubMed Scopus Google Scholar). for at of protein and by from the expression of DGAT1 and DGAT2 during adipogenesis, 3T3-L1 preadipocytes to and DGAT1 and DGAT2 expression was by DGAT1 and DGAT2 with a with a in expression in the following and and of within the two isoforms, DGAT2 a with an induction within whereas DGAT1 expression increased by the induction of DGAT2 when isolated preadipocytes differentiation, DGAT2 expression in cells isolated from the of white adipose tissue, to in In a to differentiating 3T3-L1 DGAT2 expression increased 2 following induction of with induction these observations DGAT2 expression in differentiating of cells isolated from the of adipose tissue to for and the expression of DGAT2 was a and of DGAT2 expression was within of the induction of demonstrates that the induction of DGAT2 expression in the 3T3-L1 not adipogenesis, and that DGAT2 may be an important enzyme of adipocyte synthesis in as as the importance of DGAT2, from the of the induction of this during adipogenesis and the lack of knowledge the regulation of its expression, to its regulation in developing adipocytes transcriptional mechanisms by DGAT2 is regulated during adipogenesis of gene expression an of 3T3-L1 that the temporal regulation of DGAT2 closely mimicked that of C/EBPα and A. S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google both targets of C/EBPβ Lane M.D. Mol. Cell Biol. PubMed Scopus Google Scholar, J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar). Despite the induction of C/EBPβ during adipogenesis, the of C/EBPα is C/EBPβ is to the C/EBPα promoter at in to the inhibitory of J.J. R.K. M. C. C. C.J. S. D. M. A. O'Rahilly S. Mol. Cell Biol. 2004; PubMed Scopus Google Scholar, Lane M.D. Proc. Natl. Acad. Sci. U. S. A. 2000; PubMed Scopus Google Scholar). C/EBPβ promoter in a complex and an active complex following induction Lane M.D. Genes Dev. 13: PubMed Scopus Google Scholar, N. D. L. C. J. 2003; PubMed Scopus Google Scholar). the of C/EBPα expression was by DGAT2 this to that C/EBPβ may have a key role in the regulation of its expression. is with the that of C/EBPβ in 3T3-L1 adipogenesis lipid accumulation in these this 3T3-L1 preadipocytes the inhibitory of the of the active of C/EBPβ the and to to C/EBPβ and by active of C/EBPβ P. U. Full Text PDF PubMed Scopus Google Scholar). of C/EBPβ was in or 3T3-L1 preadipocytes during by In the expression was increased to the induction of to levels to the in cells been with following induction of differentiation, expression in cells to levels those in We the of expression lipid accumulation by cells with following induction of in the or of the with expression the accumulation of lipid lipid accumulation in was to induce lipid accumulation in The expression of and was reduced by and of in these cells and Thus of the expressed was to the inhibitory of expression. We the expression of C/EBPα and in The induction of both these genes was impaired in the cells when with the cells and of DGAT2 expression in these cells demonstrated that this was by expression, a in DGAT2 of at and at with of and in C/EBPα expression at these We the expression levels of other genes regulated during adipogenesis. of differentiation, expression to of in aP2, and in in and of the induction of the 2 not The in the of for of these genes the complex of the transcription cascade. However, the that C/EBPβ has an important role in the regulation of DGAT2 in to its more adipogenesis We have demonstrated that the transcriptional as an of C/EBPβ J.J. R.K. M. C. C. C.J. S. D. M. A. O'Rahilly S. Mol. Cell Biol. 2004; PubMed Scopus Google Scholar). Thus, the of expression DGAT2 expression. with the of C/EBPβ activity by expression, expression lipid accumulation during 3T3-L1 adipogenesis However, the expression of not the expression of C/EBPβ in these cells due to its of C/EBPβ expression both C/EBPα and expression. Moreover, the induction of DGAT2 was impaired by expression, a role for C/EBPβ in DGAT2 expression The of C/EBPβ is to the expression of genes regulated by other C/EBP by to that capable of In addition, have demonstrated that C/EBPβ the of is not Thus to with C/EBPβ by to its expression. of preadipocytes with C/EBPβ in a and of expression levels at by and at by of C/EBPβ protein that this to a dramatic of C/EBPβ protein in cells with C/EBPβ We the of C/EBPβ lipid accumulation. demonstrated that loss of C/EBPβ the accumulation of lipid in a to or expression of C/EBPα and DGAT2 demonstrated that reduced induction in cells with C/EBPβ DGAT2 both and have critical roles in synthesis. However, in to their and have roles in gene expression A. L. Bowcock A. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, M. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus (179) Google Scholar). The two of and have been shown to the expression of of adipogenesis or the of these in the of lipid accumulation their expression in C/EBPβ Inhibition of C/EBPβ expression in a of in both and expression of However, of these genes was of differentiation, in the expression of more at of the The in DGAT2 expression and at and of differentiation, that the of DGAT2 expression a more contribution to the impaired lipid accumulation in these cells in AGPAT2, or However, is that the in these the of DGAT2 at the stages of differentiation, or adipogenesis observations in of adipogenesis to adipocyte development in gene expression in white adipose tissue isolated from C/EBPβ knock-out C/EBPβ was in these from studies the expression of C/EBPα was reduced as was the expression of In addition, that the expression of DGAT2 was decreased in the white adipose tissue of these mice with an important role for C/EBPβ in the expression of DGAT2 in adipocytes in We to C/EBPβ DGAT2 to its of the promoter of DGAT2 C/EBPβ within of the transcriptional These and in to these C/EBPβ and to to a control of C/EBPβ to its in the C/EBPα promoter with and shift by J.J. R.K. M. C. C. C.J. S. D. M. A. O'Rahilly S. Mol. Cell Biol. 2004; PubMed Scopus Google Scholar, Lane M.D. Genes Dev. 13: PubMed Scopus Google increased of C/EBPβ to this the of of to the that identified demonstrated that increased was for the In contrast, or of C/EBPβ to the other this used shift with from 3T3-L1 for or the C/EBPβ in the C/EBPα promoter was used as a this increased complex formation when with from differentiating cells These capable of with an to C/EBPβ from cells that been to for from differentiating preadipocytes with of the DGAT2 promoter these increased as and be with C/EBPβ These that C/EBPβ can to of the DGAT2 promoter both in vitro and in DGAT2 expression in the later stages of adipogenesis while C/EBPβ expression in differentiating 3T3-L1 cells the induction of Thus C/EBPα the regulation of DGAT2 expression in the later stages of We therefore used to C/EBPα to its expression. of 3T3-L1 preadipocytes with C/EBPα to a in its induction at and of However, as the to differentiation, the of C/EBPα was Despite assay of DGAT2 expression that this was to DGAT2 expression in these cells that C/EBP for different C/EBP isoforms, the regulation of DGAT2 by C/EBPα the same in its promoter by We therefore C/EBPα from differentiating 3T3-L1 preadipocytes and with the of the DGAT2 These an in of C/EBPα to this as with of when C/EBPα further this shift a to and from differentiating In with the assay complex formation from the and the increased as Moreover, as to later be with an to C/EBPα of this transcription to of the DGAT2 These that, during the later stages of adipogenesis, C/EBPα for C/EBPβ in the control of DGAT2 expression and that this occurs the same regulatory element in the DGAT2 of TG synthesis is likely to play an important role in the development of of adipose tissue mass. In obesity the of adipocytes with of the metabolic with the that lipid is of a detrimental of metabolic and decreased insulin C. C. R.E. 2000; PubMed Scopus Google Scholar). high TG synthesis may in cause or this the development of lipodystrophy due to mutations of AGPAT2, an enzyme in the same pathway of lipid synthesis, demonstrates the for loss of function in the TG synthesis pathway to cause metabolic in (2Agarwal A.K. Arioglu E. De Almeida S. Akkoc N. Taylor S.I. Bowcock A.M. Barnes R.I. Garg A. Nat. Genet. 2002; 31: 21-23Crossref PubMed Scopus (433) Google Scholar, 3Magre J. Delepine M. Van Maldergem L. Robert J.J. Maassen J.A. Meier M. Panz V.R. Kim C.A. Tubiana-Rufi N. Czernichow P. Seemanova E. Buchanan C.R. Lacombe D. Vigouroux C. Lascols O. Kahn C.R. Capeau J. Lathrop M. Diabetes. 2003; 52: 1573-1578Crossref PubMed Scopus (75) Google Scholar). Thus, good metabolic control control of the capacity of adipose tissue to and to the and of substrates a an appropriate of to tissues such as liver and to their to these as for However, when substrates in the adipocytes must respond to detrimental accumulation of lipids and insulin in these other a molecular the of the adipocyte to lipid and their within the is likely to regulation of the expression of key of TG synthesis. The the critical final step of TG synthesis, expressed in adipocytes, and to function as a control for lipid accumulation in these Despite this is their expression is in this or other In this to the regulation of DGAT2, its expression is more highly that of DGAT1 in differentiating preadipocytes and studies in knock-out that loss of DGAT2 leads to a lack of lipid synthesis in the (4Smith S.J. Cases S. Jensen D.R. Chen H.C. Sande E. Tow B. Sanan D.A. Raber J. Eckel R.H. Farese Jr., R.V. Nat. Genet. 2000; 25: 87-90Crossref PubMed Scopus (754) Google Scholar, S.J. Myers H.M. Watkins S.M. Brown B.E. Feingold K.R. Elias P.M. Farese Jr., R.V. J. Biol. Chem. 2004; 279: 11767-11776Abstract Full Text Full Text PDF PubMed Scopus (489) Google Scholar). to C/EBPβ expression or activity demonstrated that C/EBPβ a key role in the induction of DGAT2 during adipogenesis. The of C/EBPβ activity by LIP, or ETO, or the loss of factors such as and lipid accumulation T. N. T. S. J. 16: PubMed Scopus Google Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J.J. R.K. M. C. C. C.J. S. D. M. A. O'Rahilly S. Mol. Cell Biol. 2004; PubMed Scopus Google Scholar, N. D. J. 14: PubMed Scopus Google Scholar, Z. A. Spiegelman B.M. Cell Metab. Full Text Full Text PDF PubMed Scopus Google Scholar, T. T. N. T. S. T. Cell Metab. Full Text Full Text PDF PubMed Scopus Google Scholar). The reduced expression of factors such as and and of the induction of the genes they will make an important contribution to the lack of in these must be that of many factors in the complex of gene expression of C/EBPβ may have a role in the reduced induction of DGAT2 in is by the that of C/EBPβ in the is required to C/EBPβ at the C/EBPα promoter by L. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). Thus reduced when C/EBPβ is is likely to to reduced DGAT2 expression this In addition, that a contribution to DGAT2 expression by to its However, finding that DGAT2 is more when C/EBPβ function is impaired an important role for PPARγ. the that C/EBPβ and C/EBPα the DGAT2 promoter in cells the that regulation by these factors is likely to make a contribution to its expression during adipogenesis. is to the importance of C/EBPβ activity from the of reduced expression of C/EBPα in the control of adipocyte DGAT2 expression in C/EBPα in from fibroblasts from mice that can be to by with in combination with Despite appropriate induction of adipocyte genes such as aP2, adiponectin, and Z. E.D. S. C. Spiegelman B.M. Mol. Full Text Full Text PDF PubMed Scopus Google Scholar, B. Smith U. 2003; PubMed Scopus Google these cells lipid those from that loss of DGAT2 expression may to this of in cells leads to a dramatic of DGAT2 and lipid with its to the activity of C/EBP The of DGAT2 expression by C/EBPβ was the expression not the activity of C/EBPα be The of for or other lipogenic factors, is not and may in the DGAT2 expression and lipid accumulation in However, a to these observations is that in with control and be the of C/EBPβ by the key role of DGAT2 in the therapeutic of its expression has been in of DGAT2 in mice to of and in or diet-induced mice D. S. Chen S. S. PubMed Scopus Google Scholar). body and or fat mass not decreased in these DGAT2 mice to gain a high fat during the is with DGAT2 an important role in lipid accumulation in or adipocytes. of C/EBPβ has been shown to adipocyte and in mice S.M. L. J. M. S.J. E. C. Jensen D.R. Pulawa L.K. Eckel R.H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). will be to of DGAT2 expression to these and DGAT2 expression is regulated by C/EBPβ in the In that this is the to the regulation of DGAT2 transcription at the molecular We have shown that C/EBPβ and C/EBPα the expression of DGAT2 in developing adipocytes, for the a C/EBPβ may the expression of genes controlling lipid as as its defined role in inducing other transcription In vivo of DGAT2 has demonstrated the therapeutic of DGAT2 Thus, a of the transcriptional mechanisms controlling DGAT2 expression is important in further of in to more insight into the controlling lipid accumulation in adipose and other

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