Deletion of CGI-58 or adipose triglyceride lipase differently affects macrophage function and atherosclerosis

Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58−/− mice). CGI-58−/− macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL−/− macrophages. In contrast to ATGL−/− macrophages, however, CGI-58−/− macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58−/− macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE−/− mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor−/− mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. Cellular TG stores are efficiently hydrolyzed by adipose TG lipase (ATGL). Its coactivator comparative gene identification-58 (CGI-58) strongly increases ATGL-mediated TG catabolism in cell culture experiments. To investigate the consequences of CGI-58 deficiency in murine macrophages, we generated mice with a targeted deletion of CGI-58 in myeloid cells (macCGI-58−/− mice). CGI-58−/− macrophages accumulate intracellular TG-rich lipid droplets and have decreased phagocytic capacity, comparable to ATGL−/− macrophages. In contrast to ATGL−/− macrophages, however, CGI-58−/− macrophages have intact mitochondria and show no indications of mitochondrial apoptosis and endoplasmic reticulum stress, suggesting that TG accumulation per se lacks a significant role in processes leading to mitochondrial dysfunction. Another notable difference is the fact that CGI-58−/− macrophages adopt an M1-like phenotype in vitro. Finally, we investigated atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. In response to high-fat/high-cholesterol diet feeding, DKO animals showed comparable plaque formation as observed in ApoE−/− mice. In agreement, antisense oligonucleotide-mediated knockdown of CGI-58 in LDL receptor−/− mice did not alter atherosclerosis burden in the aortic root. These results suggest that macrophage function and atherosclerosis susceptibility differ fundamentally in these two animal models with disturbed TG catabolism, showing a more severe phenotype by ATGL deficiency. Monocyte-derived macrophages are present in virtually all tissues, where they remove apoptotic cells and cellular debris generated by tissue remodelling and/or cellular necrosis. Under pathophysiological conditions, macrophages play a key role during atherogenesis by internalizing modified lipoproteins or lipoprotein remnants that have invaded the vessel wall to form cholesterol-rich foam cells. This (along with other disease-related functions for this immune cell) has prompted profound research into the role of the macrophage, and how its functions are regulated during disease progression (1McLaren J.E. Michael D.R. Ashlin T.G. Ramji D.P. Cytokines, macrophage lipid metabolism and foam cells: implications for cardiovascular disease therapy.Prog. Lipid Res. 2011; 50: 331-347Crossref PubMed Scopus (278) Google Scholar). Comparative gene identification-58 (CGI-58) is the coactivator of adipose TG lipase (ATGL), the major TG hydrolase for the initial and rate-limiting step in lipolysis (2Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar). Lipolysis has been extensively studied in adipocytes, where under basal conditions CGI-58 binds to the surface of lipid droplets through interaction with perilipin1. Hormonal stimulation of lipolysis leads to phosphorylation of perilipin1 and hormone-sensitive lipase, resulting in the release of CGI-58 from perilipin1 to interact with and activate ATGL, which then converts TG to diacylglycerol and FA (3Zechner R. Zimmermann R. Eichmann T.O. Kohlwein S.D. Haemmerle G. Lass A. Madeo F. FAT SIGNALS–lipases and lipolysis in lipid metabolism and signaling.Cell Metab. 2012; 15: 279-291Abstract Full Text Full Text PDF PubMed Scopus (694) Google Scholar). Both mice and humans affected with ATGL or CGI-58 deficiency suffer from systemic TG accumulation, a condition called neutral lipid storage disease (NLSD) in humans (4Schweiger M. Lass A. Zimmermann R. Eichmann T.O. Zechner R. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5.Am. J. Physiol. Endocrinol. Metab. 2009; 297: E289-E296Crossref PubMed Scopus (215) Google Scholar). Of note, specific phenotypical alterations are observed depending on whether ATGL or CGI-58 is defective. The most apparent difference is the severe epidermal skin defect observed in mice and humans with CGI-58 deficiency (2Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 5Radner F.P. Streith I.E. Schoiswohl G. Schweiger M. Kumari M. Eichmann T.O. Rechberger G. Koefeler H.C. Eder S. Schauer S. et al.Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58).J. Biol. Chem. 2010; 285: 7300-7311Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar), which is absent in both species lacking ATGL (6Fischer J. Lefevre C. Morava E. Mussini J.M. Laforet P. Negre-Salvayre A. Lathrop M. Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy.Nat. Genet. 2007; 39: 28-30Crossref PubMed Scopus (365) Google Scholar, 7Haemmerle G. Lass A. Zimmermann R. Gorkiewicz G. Meyer C. Rozman J. Heldmaier G. Maier R. Theussl C. Eder S. et al.Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase.Science. 2006; 312: 734-737Crossref PubMed Scopus (1011) Google Scholar). This finding resulted in different classifications of the respective human diseases, namely NLSD with myopathy in ATGL deficiency (6Fischer J. Lefevre C. Morava E. Mussini J.M. Laforet P. Negre-Salvayre A. Lathrop M. Salvayre R. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy.Nat. Genet. 2007; 39: 28-30Crossref PubMed Scopus (365) Google Scholar), whereas CGI-58 deficiency leads to NLSD with ichthyosis (8Lefèvre C. Jobard F. Caux F. Bouadjar B. Karaduman A. Heilig R. Lakhdar H. Wollenberg A. Verret J.L. Weissenbach J. et al.Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.Am. J. Hum. Genet. 2001; 69: 1002-1012Abstract Full Text Full Text PDF PubMed Scopus (392) Google Scholar). Several ongoing studies CGI-58 and mice the and to lipid In observed in mice with CGI-58 and ATGL deficiency for an function of CGI-58 in this cell J.M. J.L. C. J. J. R. et knockdown in mice hepatic steatosis, and Lipid Res. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar, J.M. for hydrolase and adipose triglyceride lipase in lipid metabolism and 2012; PubMed Google and other as Zechner R. Haemmerle G. Comparative gene hydrolase more an adipose triglyceride lipase PubMed Scopus Google Scholar). CGI-58−/− mice to a severe skin barrier defect F.P. Streith I.E. Schoiswohl G. Schweiger M. Kumari M. Eichmann T.O. Rechberger G. Koefeler H.C. Eder S. Schauer S. et al.Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58).J. Biol. Chem. 2010; 285: 7300-7311Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar), we generated CGI-58 mice to investigate the consequences of CGI-58 deficiency in macrophages. In the present we whether CGI-58−/− macrophages the TG accumulation phenotype observed in ATGL−/− whether CGI-58 deficiency macrophage and whether the altered phenotype in atherosclerosis susceptibility in macCGI-58/ApoE-double KO (DKO) animals. have that of ATGL in macrophages macrophage phenotype and as TG-rich lipid accumulation, apoptosis E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google and endoplasmic reticulum E. P. B. S. M. Koefeler H. et is for apoptosis in 2012; 3: PubMed Scopus Google Scholar), E. P. H. S. J.G. Eder S. Kohlwein S.D. et cell and in macrophages with defective 2011; PubMed Scopus Google Scholar), and decreased B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar). In of ATGL−/− into LDL mice that the of ATGL in immune cells atherosclerosis susceptibility B. E. B. R. J. et adipose triglyceride lipase deficiency in lipoprotein Biol. 2011; PubMed Scopus Google Scholar). the coactivator of ATGL, we that the of CGI-58 in macrophages leads to TG-rich lipid that of the ATGL coactivator CGI-58 in myeloid cells macrophage function in and in and atherosclerosis with a targeted deletion of CGI-58 in myeloid cells (macCGI-58−/− generated by mice Eder S. Rechberger F.P. G. A. Kumari M. et lipolysis in mice on comparative gene Biol. Chem. Full Text Full Text PDF PubMed Scopus Google by of with mice that under the of the murine C. R. gene in macrophages and Res. PubMed Scopus Google by of mice as with animals. To investigate atherosclerosis we generated as and mice by and mice with ApoE−/− mice the and mice a diet fat and protein with a diet or a high-fat/high-cholesterol diet for the of with on a in a and lipid a atherosclerosis studies antisense knockdown of CGI-58, mice a diet in and of energy as for in with of a or CGI-58 as J.M. J.L. C. J. J. R. et knockdown in mice hepatic steatosis, and Lipid Res. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar). by of and and of diet and for lipid and lipoprotein The of animal to the by the of and of and The knockdown studies of CGI-58 in an for of animal and all by the and the of or the macrophages an of the with The cells in and for the cells with and the cells in and for macrophages from and with in and macrophage for To in macrophages with or for in by the studies macrophages of of into the of mice that been with and a diet for as J.M. S. C. R. et of and from PubMed Scopus Google Scholar). of cells by with and macrophages for J.M. J.L. C. J. J. R. et knockdown in mice hepatic steatosis, and Lipid Res. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar). from mice or from and by for and FA by atherosclerosis studies knockdown of CGI-58, of and TG by In lipoproteins by protein and in lipoprotein an as J.M. S. C. R. et of and from PubMed Scopus Google Scholar). for in the cells with with for of in and the lipid under a of The in for in a and by of the with the The to protein a the of cells in for FA in the TG by lipid by and the with TG with and in as and as H. M. H. of in the lipoprotein by of of PubMed Scopus Google Scholar). on in and for with and with Lipid droplets by an and a with of on for with and protein a The TG and of The per and of of protein from cell with of and in a for The by the of and of and M. Eichmann T.O. Zimmermann R. Zechner R. Lass A. of PubMed Scopus Google Scholar). The for and for The in of the by and the release of in with and of for under the per and in under a of of and and the on and on of human as from a of for and and of to the as B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar). from macrophages a cell on a of by the on a the of murine as gene on all as for in and the for and of results in Res. PubMed Google Scholar). are in the of macrophages from the different or by to or with and protein protein or and ATGL or by a in cell culture a of cells per cells and for in with with or and in a The an with basal by of and to protein or as a of the mitochondrial in the of in of in and cells in and or for and with of E. in The and of to the of the and on a to the protein of To in mice with of E. in macrophages by the with and in and for The cells with and and to and intracellular to protein by and cells with and cells for on a for to with to from the and and an of from a in the aortic and of ApoE−/− and animals of and the in with for a in the with for the in of the in with by from the of the for the of macrophages a as as for in and with as A. M. G. M. S. 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These that CGI-58−/− macrophages of mitochondrial stress, and mitochondrial as observed in ATGL−/− macrophages. To whether the of CGI-58 in macrophages comparable to ATGL deficiency B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar), we in and in observed decreased in CGI-58−/− with macrophages, of To whether decreased to the phagocytic of CGI-58−/− macrophages, we the of of and however, comparable CGI-58−/− and macrophages we whether basal and are in mitochondria of CGI-58−/− macrophages in the or of and of the that mitochondria of CGI-58−/− macrophages with mitochondria from mice in both conditions as of that mitochondria from CGI-58−/− macrophages are to and by In we observed mitochondrial surface and protein of and in CGI-58−/− macrophages. In to decreased in mice This however, no are a and cell of activated macrophages and activated macrophages with A. A. M. and PubMed Scopus Google Scholar). have that ATGL−/− macrophages adopt an phenotype E. P. H. S. J.G. Eder S. Kohlwein S.D. et cell and in macrophages with defective 2011; PubMed Scopus Google Scholar). To investigate the phenotype of CGI-58−/− macrophages, we of and These an of the of the and of and in CGI-58−/− with macrophages In with of the D.R. S. M. M. of macrophage and by the 2011; PubMed Scopus Google in the of CGI-58−/− with cells the M1-like of CGI-58−/− macrophages. To the consequences of CGI-58−/− deficiency and the TG accumulation in myeloid cells on we generated and mice and with a to observed no in lipid and DKO and ApoE−/− mice. from both show the which is in contrast to we observed in CGI-58−/− with macrophages. of aortic no in formation and which to macrophages and comparable in from ApoE−/− and DKO mice of plaque in aortic a in in aortic of mice lipid of ApoE−/− and mice diet or with for in a new atherosclerosis susceptibility by CGI-58 deficiency. 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R. et knockdown in mice hepatic steatosis, and Lipid Res. 2010; Full Text Full Text PDF PubMed Scopus Google Scholar). we show that macrophages from mice have a in macrophage CGI-58 as this we that CGI-58 knockdown in macrophages and other has no significant on or TG in mice CGI-58 knockdown did not alter or to mice knockdown of CGI-58 did not alter atherosclerosis burden in the aortic or of mice as by these results that CGI-58 in macrophages, and adipose tissue by CGI-58 or deficiency of CGI-58 in myeloid cells has on atherosclerosis to the in macrophages lacking ATGL E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar, E. P. B. S. M. Koefeler H. et is for apoptosis in 2012; 3: PubMed Scopus Google Scholar, E. P. H. S. J.G. Eder S. Kohlwein S.D. et cell and in macrophages with defective 2011; PubMed Scopus Google Scholar, B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar), we that the of its coactivator CGI-58 results in alterations of macrophage To investigate the consequences of CGI-58 deficiency in macrophages, we generated a lacking CGI-58 in myeloid cells macrophages, and These mice are with no apparent in skin with the of CGI-58 in myeloid cells not lipid and mice are with in mice is to the results by et H. J. F. M. C. M. et CGI-58 deficiency to in Full Text Full Text PDF PubMed Scopus Google Scholar), impaired in mice. This is to as both and to we have the in mice that significant the not a difference leading to the results CGI-58 deficiency leads to decreased TG and a TG-rich lipid accumulation in macrophages, to ATGL−/− macrophages E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar, B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar). These results suggest that ATGL by CGI-58 as protein (2Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (673) Google in macrophages. and as as in FA CGI-58−/− and macrophages. is for the of TG and the of in cells and tissues, these results that generated by the of are by CGI-58−/− and macrophages. and with comparable hydrolase and CGI-58−/− macrophages, as observed in ATGL−/− macrophages B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar). In contrast to et H. J. F. M. C. M. et CGI-58 deficiency to in Full Text Full Text PDF PubMed Scopus Google and and in macrophages of mice. the in the two studies are to or conditions of the macrophages to of FA TG of CGI-58−/− macrophages of all and with the in and FA has not been in ATGL−/− macrophages, in adipose tissue of ATGL−/− mice. are different to these results T.O. Kumari M. Zimmermann R. Lass A. Zechner R. on the and of adipose triglyceride lipase, hormone-sensitive lipase, and Biol. Chem. 2012; Full Text Full Text PDF PubMed Scopus Google Scholar), where the showed that ATGL FA in with a for mitochondria in ATGL−/− macrophages are of the mitochondrial apoptosis as a of defective lipolysis E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar). the phenotype in CGI-58−/− macrophages. of cell as of on the by and protein of and of mitochondria to cell however, that mitochondrial apoptosis is not in CGI-58−/− macrophages. protein and of the and that CGI-58 deficiency in macrophages not These results are different from in ATGL−/− macrophages, where we observed of apoptosis E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google and E. P. B. S. M. Koefeler H. et is for apoptosis in 2012; 3: PubMed Scopus Google Scholar). of macrophages with resulted in the apoptotic phenotype and of mitochondria as observed in ATGL−/− macrophages E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar). these we that intracellular TG accumulation is to mitochondrial and cell in macrophages. The results from the present are TG accumulation leads to mitochondrial in ATGL−/− and macrophages E. B. J. A. H. Kohlwein S.D. et accumulation the mitochondrial apoptosis in Biol. Chem. 2011; Full Text Full Text PDF PubMed Scopus Google Scholar), to CGI-58−/− macrophages, is ATGL is present in CGI-58−/− macrophages, that is basal ATGL-mediated TG hydrolase which is to the cell from mitochondrial macrophage TG are comparable ATGL−/− and CGI-58−/− macrophages, suggesting other to for cell mitochondrial and in ATGL−/− macrophages. The in phagocytic affected by the of ATGL B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google and CGI-58 in a with in and with macrophages. has been that of cellular TG by ATGL is to as for and that ATGL deficiency leads to mitochondrial and G. G. S. A. M. Kienesberger et fat catabolism mitochondrial function and 2011; PubMed Scopus Google Scholar). of in macrophages decreased mitochondrial to the phagocytic of CGI-58−/− macrophages. the surface of mitochondria by CGI-58 the is to the in as energy decreased in macrophages H. J. F. M. C. M. et CGI-58 deficiency to in Full Text Full Text PDF PubMed Scopus Google Scholar). in finding of not in in where we observed a to however, that the for this is the difference in the in CGI-58 is absent in myeloid cells macrophages, in which is affected in vitro. In the decreased in in ATGL−/− mice B. E. M. E. C. F. Haemmerle G. Zechner R. et triacylglycerol by adipose triglyceride Biol. Chem. 2010; 285: Full Text Full Text PDF PubMed Scopus Google Scholar). is a energy FA in ATGL−/− mice G. Lass A. Zimmermann R. Gorkiewicz G. Meyer C. Rozman J. Heldmaier G. Maier R. Theussl C. Eder S. et al.Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase.Science. 2006; 312: 734-737Crossref PubMed Scopus (1011) Google FA in mice the observed in in phagocytic to the observed ATGL−/− and CGI-58−/− macrophages, we in the of deficiency on atherosclerosis plaque of macrophages, and in aortic of and ApoE−/− mice. In with these of the aortic comparable in both we per of the we plaque formation in DKO mice. In agreement, knockdown of CGI-58 in mice did not alter atherosclerosis burden in the aortic atherosclerosis in the these are to we observed in the of ATGL, where of ATGL−/− into mice resulted in plaque formation B. E. B. R. J. et adipose triglyceride lipase deficiency in lipoprotein Biol. 2011; PubMed Scopus Google Scholar). different models in these two results that the of ATGL or CGI-58 in myeloid cells results in different by ATGL deficiency and or plaque formation by of This difference in plaque formation is to in of the macrophages lacking ATGL or CGI-58 show comparable as cells. The of ATGL−/− macrophages and the M1-like phenotype of CGI-58−/− in to the in plaque In with et H. J. F. M. C. M. et CGI-58 deficiency to in Full Text Full Text PDF PubMed Scopus Google have that macrophage CGI-58 deficiency the to in mice. from CGI-58−/− macrophages, suggesting that the of CGI-58 in macrophages the response to This finding is in with results from CGI-58 knockdown in which lipid generated by CGI-58 to in the and a role of CGI-58 in J.L. J. G. S. M. et systemic and 2012; PubMed Scopus Google Scholar). an ApoE−/− however, and macrophage no different mice that or CGI-58 in macrophages. macrophage from to the phenotype R. C. G. M. J. H. A. et phenotype in Biol. 2011; PubMed Scopus Google Scholar), that the of macrophages into an M1-like which by CGI-58 deficiency. In plaque formation in aortic of mice with ATGL−/− with decreased macrophage B. E. B. R. J. et adipose triglyceride lipase deficiency in lipoprotein Biol. 2011; PubMed Scopus Google Scholar). The in this that the TG-rich lipid accumulation ATGL−/− macrophages is not the for atherosclerosis as of CGI-58 in macrophages results in comparable TG accumulation, results different CGI-58−/− and ATGL−/− of stress, mitochondrial and mitochondrial as as M1-like of CGI-58−/− macrophages, and in atherosclerosis susceptibility for different and/or of CGI-58 in macrophages of that of the a more severe phenotype of the The M. 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