Hematopoietic ABCA1 deletion promotes monocytosis and worsens diet-induced insulin resistance in mice

Low-grade chronic inflammation plays an important role in the pathogenesis of obesity-induced insulin resistance. ABCA1 is essential for reverse cholesterol transport and HDL synthesis, and protects against macrophage inflammation. In the present study, the effects of ABCA1 deficiency in hematopoietic cells on diet-induced inflammation and insulin resistance were tested in vivo using bone marrow transplanted (BMT)-WT and BMT-ABCA1−/− mice. When challenged with a high-fat high-carbohydrate diabetogenic diet with added cholesterol (HFHSC), BMT-ABCA1−/− mice displayed enhanced insulin resistance and impaired glucose tolerance as compared with BMT-WT mice. The worsened insulin resistance and impaired glucose tolerance in BMT-ABCA1−/− mice were accompanied by increased macrophage accumulation and inflammation in adipose tissue and liver. Moreover, BMT-ABCA1−/− mice had significantly higher hematopoietic stem cell proliferation, myeloid cell expansion, and monocytosis when challenged with the HFHSC diet. In vitro studies indicated that macrophages from ABCA1−/− mice showed significantly increased inflammatory responses induced by saturated fatty acids. Taken together, these studies point to an important role for hematopoietic ABCA1 in modulating a feed-forward mechanism in obesity such that inflamed tissue macrophages stimulate the production of more monocytes, leading to an exacerbation of inflammation and associated disease processes. Low-grade chronic inflammation plays an important role in the pathogenesis of obesity-induced insulin resistance. ABCA1 is essential for reverse cholesterol transport and HDL synthesis, and protects against macrophage inflammation. In the present study, the effects of ABCA1 deficiency in hematopoietic cells on diet-induced inflammation and insulin resistance were tested in vivo using bone marrow transplanted (BMT)-WT and BMT-ABCA1−/− mice. When challenged with a high-fat high-carbohydrate diabetogenic diet with added cholesterol (HFHSC), BMT-ABCA1−/− mice displayed enhanced insulin resistance and impaired glucose tolerance as compared with BMT-WT mice. The worsened insulin resistance and impaired glucose tolerance in BMT-ABCA1−/− mice were accompanied by increased macrophage accumulation and inflammation in adipose tissue and liver. Moreover, BMT-ABCA1−/− mice had significantly higher hematopoietic stem cell proliferation, myeloid cell expansion, and monocytosis when challenged with the HFHSC diet. In vitro studies indicated that macrophages from ABCA1−/− mice showed significantly increased inflammatory responses induced by saturated fatty acids. Taken together, these studies point to an important role for hematopoietic ABCA1 in modulating a feed-forward mechanism in obesity such that inflamed tissue macrophages stimulate the production of more monocytes, leading to an exacerbation of inflammation and associated disease processes. Low-grade inflammation has emerged as an important contributor to the etiology of insulin resistance in obesity and type 2 diabetes (1.Hotamisligil G.S. Shargill N.S. Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.Science. 1993; 259: 87-91Crossref PubMed Scopus (6135) Google Scholar). Adipose tissue macrophages appear to be responsible for much of the increase in inflammation in adipose tissue with obesity (1.Hotamisligil G.S. Shargill N.S. Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance.Science. 1993; 259: 87-91Crossref PubMed Scopus (6135) Google Scholar, 2.Xu H. 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Boudyguina E. Mulya A. Gebre A.K. Willingham M.C. Hiltbold E.M. Mishra N. et al.Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages.J. Biol. Chem. 2008; 283: 22930-22941Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar). The addition of a relatively small amount of dietary cholesterol results in a marked increase in the accumulation of macrophages in adipose tissue (9.Subramanian S. Han C.Y. Chiba T. McMillen T.S. Wang S.A. Haw 3rd, A. Kirk E.A. O'Brien K.D. Chait A. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice.Arterioscler. Thromb. Vasc. Biol. 2008; 28: 685-691Crossref PubMed Scopus (144) Google Scholar). Mice with macrophage-specific transgenic expression of cholesterol ester hydrolase, which results in significant cholesterol ester and free reduction in macrophages, reduces macrophage infiltration and improves insulin sensitivity (10.Bie J. Zhao B. Song J. Ghosh S. Improved insulin sensitivity in high fat- and high cholesterol-fed Ldlr-/- mice with macrophage-specific transgenic expression of cholesteryl ester hydrolase: role of macrophage inflammation and infiltration into adipose tissue.J. Biol. Chem. 2010; 285: 13630-13637Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 11.Zhao B. Song J. Chow W.N. St. Clair R.W. Rudel L.L. Ghosh S. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr mice.J. Clin. Invest. 2007; 117: 2983-2992Crossref PubMed Scopus (109) Google Scholar). Moreover, deficiency of ABCA1 and ABCG1 promotes monocytosis (12.Murphy A.J. Dragoljevic D. Tall A.R. Cholesterol efflux pathways regulate myelopoiesis: a potential link to altered macrophage function in atherosclerosis.Front. Immunol. 2014; 5: 490Crossref PubMed Scopus (39) Google Scholar, 13.Yvan-Charvet L. Pagler T. Gautier E.L. Avagyan S. Siry R.L. Han S. Welch C.L. Wang N. Randolph G.J. Snoeck H.W. et al.ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.Science. 2010; 328: 1689-1693Crossref PubMed Scopus (525) Google Scholar). These studies suggest that cholesterol metabolism plays an important role in macrophage infiltration and inflammation in peripheral tissues, including adipose tissue and liver. ABCA1 is a cell-membrane protein that is essential for HDL synthesis and reverse cholesterol transport. ABCA1 protects against cholesterol accumulation in macrophages by transporting cholesterol and phospholipids to apolipoproteins from cells (14.Oram J.F. ATP-binding cassette transporter A1 and cholesterol trafficking.Curr. Opin. 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Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions.Circulation. 2008; 118: 1837-1847Crossref PubMed Scopus (342) Google Scholar, 8.Zhu X. Lee J.Y. Timmins J.M. Brown J.M. Boudyguina E. Mulya A. Gebre A.K. Willingham M.C. Hiltbold E.M. Mishra N. et al.Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages.J. Biol. Chem. 2008; 283: 22930-22941Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar, C. Vaughan A.M. J.F. The macrophage cholesterol exporter ABCA1 functions as an Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the role of macrophages in the of inflammatory signaling in adipose tissue and that of ABCA1 in cells increase macrophage tissue accumulation, and insulin resistance in response to a diabetogenic diet. mice with ABCA1 in hematopoietic cells using bone marrow results that when challenged with a high-fat high-carbohydrate diabetogenic diet with added cholesterol (9.Subramanian S. Han C.Y. Chiba T. McMillen T.S. Wang S.A. Haw 3rd, A. Kirk E.A. O'Brien K.D. Chait A. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice.Arterioscler. Thromb. Vasc. Biol. 2008; 28: 685-691Crossref PubMed Scopus (144) Google mice in ABCA1 in hematopoietic increased hematopoietic stem cell proliferation, myeloid cell expansion, macrophage accumulation, and inflammation in adipose tissue and as as more diet-induced insulin resistance. suggest an important role for hematopoietic ABCA1 in a feed-forward mechanism in obesity such that inflamed tissue macrophages stimulate the production of more monocytes, leading to an exacerbation of inflammation and associated disease processes. mice in the were of the in and on a ABCA1−/− mice were a from and the and of ABCA1−/− mice has been J. D. T. C. C. J. et deficiency and cell accumulation in mice with of ATP-binding cassette Natl. Acad. Sci. USA. PubMed Scopus Google Scholar). bone marrow from and ABCA1−/− mice by the marrow of the with were into mice. a mice were on a HFHSC diet for to were of diet. tissues were in and were with and in were with from the and of the of in the mice were in blood from the a Cholesterol and in and were using insulin were using an glucose and insulin tolerance were a and of diet as (9.Subramanian S. Han C.Y. Chiba T. McMillen T.S. Wang S.A. Haw 3rd, A. Kirk E.A. O'Brien K.D. Chait A. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice.Arterioscler. Thromb. Vasc. Biol. 2008; 28: 685-691Crossref PubMed Scopus (144) Google Scholar). on mice using from cells using a to the 2 of and the by for were from and were as the of the gene were using the fat and were and to by in were with for by for 2 with for by a with ABC The of cells for as the of of cells by the of and blood cell were from blood using a cell Adipose macrophages were using as (9.Subramanian S. Han C.Y. Chiba T. McMillen T.S. Wang S.A. Haw 3rd, A. Kirk E.A. O'Brien K.D. Chait A. Dietary cholesterol worsens adipose tissue macrophage accumulation and atherosclerosis in obese LDL receptor-deficient mice.Arterioscler. Thromb. Vasc. Biol. 2008; 28: 685-691Crossref PubMed Scopus (144) Google Scholar). white adipose tissue from mice the of and in were using St. The a cell and cells were The for using cells were on an to blood and hematopoietic stem as L. Pagler T. Gautier E.L. Avagyan S. Siry R.L. Han S. Welch C.L. Wang N. Randolph G.J. Snoeck H.W. et al.ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation.Science. 2010; 328: 1689-1693Crossref PubMed Scopus (525) Google Scholar). cells were with a and were using to the blood and myeloid blood cells were using blood cell were as and into and myeloid cells were as cell cells were from to blood and stem cells and cells were as and and the myeloid cells were as cells were from using were on the and using macrophages were as C. J.F. The cell cholesterol exporter ABCA1 as a from cardiovascular disease and PubMed Scopus Google and in with for 2 cells were and the to with fatty were with LDL expression cells were with of in and fatty for with the indicated fatty fatty to fatty and and for cells were from to blood and in for 2 to cells in to The cells were for in stem cell and 2 cells were with 2 for and the into the cells by were using the and as and to when to and to of the to be the potential role of ABCA1 in obesity-induced inflammation and insulin resistance in bone marrow transplanted (BMT)-WT and BMT-ABCA1−/− by from ABCA1−/− and into a mice were on diet to the HFHSC diet for to that were in and macrophage accumulation BMT-WT and BMT-ABCA1−/− mice on the diet. the HFHSC diet increased and were significant BMT-WT and BMT-ABCA1−/− mice with the Eck M. Bos I.S. Kaminski W.E. Orso E. Rothe G. Twisk J. Bottcher A. Van Amersfoort E.S. Christiansen-Weber T.A. Fung-Leung W.P. et al.Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.Proc. Natl. Acad. Sci. USA. 2002; 99: 6298-6303Crossref PubMed Scopus (320) Google Scholar, 19.Brunham L.R. Singaraja R.R. Duong M. Timmins J.M. Fievet C. Bissada N. Kang M.H. Samra A. Fruchart J.C. B. et of ABCA1 susceptibility to Thromb. Vasc. Biol. PubMed Scopus Google cholesterol and HDL cholesterol were significantly HFHSC BMT-WT and BMT-ABCA1−/− mice indicated that the were HFHSC BMT-WT and BMT-ABCA1−/− mice and glucose and the were significantly higher for the HFHSC BMT-ABCA1−/− mice compared with of HFHSC BMT-WT mice. These suggest that HFHSC BMT-ABCA1−/− mice were more insulin ABCA1 worsened insulin resistance. BMT-WT and BMT-ABCA1−/− mice were the HFHSC diet for glucose and insulin were glucose tolerance insulin tolerance the to the of the glucose tolerance to the of the insulin tolerance BMT-WT glucose and insulin tolerance in HFHSC BMT-WT and BMT-ABCA1−/− mice. shown in significantly glucose and insulin tolerance were in HFHSC BMT-ABCA1−/− mice as compared with HFHSC BMT-WT mice. In macrophages adipose tissue promote insulin resistance J.M. The cellular and signaling the and metabolism in PubMed Scopus Google Scholar). hematopoietic ABCA1 deficiency macrophage accumulation in adipose the macrophage of white adipose that of and expression were significantly in adipose tissue of HFHSC BMT-ABCA1−/− mice. Moreover, cell of the showed that the of cells significantly higher in adipose tissue of HFHSC BMT-ABCA1−/− increased macrophage the inflammatory of adipose tissue and that adipose tissue and the from HFHSC BMT-ABCA1−/− mice had significantly higher expression of and is tissue that to insulin resistance in obesity and a significant of macrophages the of liver. that when the HFHSC BMT-ABCA1−/− mice had significantly expression of and in the with the increase of of significantly in the of HFHSC BMT-ABCA1−/− mice higher macrophage the expression of inflammatory in the liver. In with the increase in macrophage accumulation in the of HFHSC BMT-ABCA1−/− a marked increase in the expression of inflammatory and with the in insulin significantly in the of BMT-ABCA1−/− mice as compared with BMT-WT controls with insulin is a obesity and of the myeloid K. Yamane K. Hanafusa M. Mori H. Mito K. Okubo M. Hara H. Kohno N. Elevated white blood cell count in subjects with impaired glucose tolerance.Diabetes Care. 2004; 27: 491-496Crossref PubMed Scopus (75) Google Scholar, M.I. Duncan B.B. A.R. G. S. M.I. G. of inflammation and of diabetes in in a Full Text Full Text PDF PubMed Scopus Google Scholar). recent has shown that and monocytosis macrophage accumulation and insulin resistance in obesity (4.Nagareddy P.R. Kraakman M. Masters S.L. Stirzaker R.A. Gorman D.J. Grant R.W. Dragoljevic D. Hong E.S. Abdel-Latif A. Smyth S.S. et al.Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Cell Metab. 2014; 19: 821-835Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar). for the increased macrophage accumulation and insulin resistance in the BMT-ABCA1−/− mice is that higher blood of and and blood were from blood using a cell and and cells were using shown in on the diet were in blood cells BMT-WT and BMT-ABCA1−/− mice. with (4.Nagareddy P.R. Kraakman M. Masters S.L. Stirzaker R.A. Gorman D.J. Grant R.W. Dragoljevic D. Hong E.S. Abdel-Latif A. Smyth S.S. et al.Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Cell Metab. 2014; 19: 821-835Abstract Full Text Full Text PDF PubMed Scopus (316) Google diet-induced obese BMT-WT mice showed in the of and diet as HFHSC BMT-WT blood indicated that HFHSC BMT-ABCA1−/− mice increased the of peripheral and had indicated that a significant increase in blood myeloid cells with a increase in the and in the HFHSC BMT-ABCA1−/− mice compared with HFHSC BMT-WT mice The of the HFHSC BMT-ABCA1−/− mice a hematopoietic stem cells and and in mice. myeloid and were significantly increased in HFHSC BMT-ABCA1−/− mice as compared with HFHSC BMT-WT mice. Moreover, the showed a increase in HFHSC BMT-ABCA1−/− mice an in vitro and that HFHSC BMT-ABCA1−/− displayed significantly increased compared with BMT-WT in response to These suggest that increased and of be responsible for the monocytosis and that in the BMT-ABCA1−/− mice the HFHSC diet. Obesity and type 2 diabetes by fatty and fatty inflammatory which been to to insulin resistance. and shown that macrophage ABCA1 deficiency pro-inflammatory the role of the ABCA1 in fatty inflammation in macrophages is ABCA1 deficiency in macrophages fatty pro-inflammatory which in insulin resistance. macrophages from ABCA1−/− and mice were cholesterol by LDL and for with free fatty fatty The expression of inflammatory were by showed in ABCA1 deficiency significantly increased the fatty expression of and the ABCA1 fatty pro-inflammatory macrophages with for the and the cells with free fatty for shown in cells with which cholesterol efflux and the significantly fatty and expression in in ABCA1−/− These suggest that of the ABCA1 significantly fatty macrophage inflammation. that of ABCA1 in hematopoietic cells worsens diet-induced and insulin resistance. the worsened insulin in adipose tissue and of mice in with increased macrophage accumulation and enhanced inflammatory expression in these In of ABCA1 in hematopoietic cells results in significantly higher hematopoietic stem cell proliferation, myeloid cell expansion, and monocytosis when challenged with the HFHSC diet. that ABCA1 deficiency free fatty pro-inflammatory gene expression in with the important of macrophage inflammation and monocytosis in promoting insulin resistance in diet-induced obesity (4.Nagareddy P.R. Kraakman M. Masters S.L. Stirzaker R.A. Gorman D.J. Grant R.W. Dragoljevic D. Hong E.S. Abdel-Latif A. Smyth S.S. et al.Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Cell Metab. 2014; 19: 821-835Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar, McMillen T.S. H. N. J.F. C. Obesity and in increased adipose tissue ABCG1 expression in PubMed Scopus Google Scholar, A.R. Obesity a in adipose tissue macrophage Clin. Invest. 2007; 117: PubMed Scopus Google Scholar). results suggest that hematopoietic ABCA1 is an important regulator of monocytosis and macrophage accumulation in diet-induced a role in diet-induced obesity and development of insulin resistance. Adipose tissue macrophages from mice of macrophages that adipose tissue from diet-induced obesity to a in the to a pro-inflammatory to insulin resistance S.P. McCann D. Desai M. Rosenbaum M. Leibel R.L. Ferrante Jr, A.W. Obesity is associated with macrophage accumulation in adipose tissue.J. Clin. Invest. 2003; 112: 1796-1808Crossref PubMed Scopus (7456) Google Scholar, A.R. Obesity a in adipose tissue macrophage Clin. Invest. 2007; 117: PubMed Scopus Google Scholar, A.R. Increased inflammatory of adipose tissue macrophages diet-induced 2007; PubMed Scopus Google Scholar). is a obesity and of the myeloid K. Yamane K. Hanafusa M. Mori H. Mito K. Okubo M. Hara H. Kohno N. Elevated white blood cell count in subjects with impaired glucose tolerance.Diabetes Care. 2004; 27: 491-496Crossref PubMed Scopus (75) Google Scholar, M.I. Duncan B.B. A.R. G. S. M.I. G. of inflammation and of diabetes in in a Full Text Full Text PDF PubMed Scopus Google Scholar). studies by (4.Nagareddy P.R. Kraakman M. Masters S.L. Stirzaker R.A. Gorman D.J. Grant R.W. Dragoljevic D. Hong E.S. Abdel-Latif A. Smyth S.S. et al.Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Cell Metab. 2014; 19: 821-835Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar) shown that and monocytosis macrophage accumulation and insulin resistance in obesity a feed-forward such that inflamed tissue macrophages stimulate the production of more monocytes, leading to an exacerbation of inflammation and associated disease (4.Nagareddy P.R. Kraakman M. Masters S.L. Stirzaker R.A. Gorman D.J. Grant R.W. Dragoljevic D. Hong E.S. Abdel-Latif A. Smyth S.S. et al.Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity.Cell Metab. 2014; 19: 821-835Abstract Full Text Full Text PDF PubMed Scopus (316) Google Scholar). results with feed-forward on a in which deficiency of ABCA1 in macrophages tissue macrophage by inflammatory of the hematopoietic cells to ABCA1 deficiency in in more macrophage accumulation, and insulin resistance. with and shown that of ABCA1 results in an increased macrophage inflammatory response to (7.Yvan-Charvet L. Welch C. Pagler T.A. Ranalletta M. Lamkanfi M. Han S. Ishibashi M. Li R. Wang N. Tall A.R. Increased inflammatory gene expression in ABC transporter-deficient macrophages: free cholesterol accumulation, increased signaling via toll-like receptors, and neutrophil infiltration of atherosclerotic lesions.Circulation. 2008; 118: 1837-1847Crossref PubMed Scopus (342) Google Scholar, 8.Zhu X. Lee J.Y. Timmins J.M. Brown J.M. Boudyguina E. Mulya A. Gebre A.K. Willingham M.C. Hiltbold E.M. Mishra N. et al.Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages.J. Biol. Chem. 2008; 283: 22930-22941Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar, C. Vaughan A.M. J.F. The macrophage cholesterol exporter ABCA1 functions as an Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and free fatty studies suggest an ABCA1 expression and chronic inflammation S. E.S. M. Tall A.R. Increased and inflammation in ABCA1 with by Thromb. Vasc. Biol. PubMed Scopus Google Scholar). has been shown that hematopoietic of ABCA1 promotes hematopoietic stem cell and monocytosis Eck M. Bos I.S. Kaminski W.E. Orso E. Rothe G. Twisk J. Bottcher A. Van Amersfoort E.S. Christiansen-Weber T.A. Fung-Leung W.P. et al.Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.Proc. Natl. Acad. Sci. USA. 2002; 99: 6298-6303Crossref PubMed Scopus (320) Google Scholar, L. Ranalletta M. Wang N. Han S. N. Li R. Welch C. Tall A.R. deficiency of ABCA1 and ABCG1 promotes cell accumulation and atherosclerosis in mice.J. Clin. Invest. 2007; 117: PubMed Scopus Google Scholar). Taken together, these studies suggest that hematopoietic ABCA1 deficiency as an of the feed-forward mechanism that promotes diet-induced insulin resistance. to hematopoietic ABCA1 feed-forward mechanism and diet-induced insulin resistance. macrophage mice increased macrophage in glucose and increased insulin resistance on a HFHSC diet. that hematopoietic ABCA1 is crucial in macrophage accumulation and insulin resistance in response to dietary fat and that of hematopoietic ABCA1 and the increase in macrophage accumulation in the and adipose tissue to glucose in to study, a by et X. S. X. Brown M. J. H. Gebre A.K. Boudyguina E. et ABCA1 insulin resistance in diet-induced obese Lipid Res. 2013; Full Text Full Text PDF PubMed Scopus Google Scholar) in insulin sensitivity in mice macrophage using the studies the of ABCA1 in hematopoietic In the to expression is to macrophages and X. S. X. Brown M. J. H. Gebre A.K. Boudyguina E. et ABCA1 insulin resistance in diet-induced obese Lipid Res. 2013; Full Text Full Text PDF PubMed Scopus Google Scholar). that the increased inflammation and insulin sensitivity in mice is to of ABCA1 in cell to of ABCA1 in cells in addition to in significantly higher hematopoietic stem cell proliferation, myeloid cell expansion, and These suggest that of ABCA1 in myeloid cells macrophages is and that ABCA1 in hematopoietic cells is to promote diet-induced insulin resistance. Interestingly, the results were in studies of atherosclerosis and mice. in atherosclerosis in mice using showed increased atherosclerosis in of Eck M. Bos I.S. Kaminski W.E. Orso E. Rothe G. Twisk J. Bottcher A. Van Amersfoort E.S. Christiansen-Weber T.A. Fung-Leung W.P. et al.Leukocyte ABCA1 controls susceptibility to atherosclerosis and macrophage recruitment into tissues.Proc. Natl. Acad. Sci. USA. 2002; 99: 6298-6303Crossref PubMed Scopus (320) Google Scholar, 19.Brunham L.R. Singaraja R.R. Duong M. Timmins J.M. Fievet C. Bissada N. Kang M.H. Samra A. Fruchart J.C. B. et of ABCA1 susceptibility to Thromb. Vasc. Biol. PubMed Scopus Google Scholar, D. L. S. T. M. Increased atherosclerosis in mice with of ABCA1 in Thromb. Vasc. Biol. 2002; PubMed Scopus Google Scholar, X. X. C. S. Q. M. Boudyguina E. Gebre A.K. Brown et ATP-binding cassette transporter A1 has on in mice.Arterioscler. Thromb. Vasc. Biol. 2014; PubMed Scopus Google Scholar). These studies a role for hematopoietic cell ABCA1 and associated monocytosis in as as insulin resistance. In results that of ABCA1 in hematopoietic cells to on adipose and macrophage inflammation in mice. when mice obese and is a to against ABCA1 is important for adipose and macrophage in insulin ABCA1 an important of to the effects of the of ABCA1 in cells as a potential for the of insulin resistance as as The for the and of by Chait of of bone marrow bone marrow transplanted stem cell high-fat high-carbohydrate diabetogenic diet with added cholesterol cell myeloid cell

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