ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity

Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1−ad/−ad). When fed a high-fat, high-cholesterol diet, ABCA1−ad/−ad mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1−ad/−ad mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis. Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1−ad/−ad). When fed a high-fat, high-cholesterol diet, ABCA1−ad/−ad mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1−ad/−ad mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis. Adipose tissue has a crucial role in energy metabolism because it is the major storage site for TGs. Furthermore, adipose tissue is an important exocrine organ secreting various adipokines important in metabolism (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar). In addition to being the main site for TG storage, adipose tissue also contains one of the largest pools of cholesterol in the body (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, 4Kovanen P.T. Nikkilä E.A. Miettinen T.A. Regulation of cholesterol synthesis and storage in fat cells.J. Lipid Res. 1975; 16: 211-223Abstract Full Text PDF PubMed Google Scholar). Cholesterol and TGs are taken up by adipocytes from plasma lipoproteins via lipoprotein receptors including the LDL receptor (LDLR), scavenger receptor B1 (SR-B1), and CD36 (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, 4Kovanen P.T. Nikkilä E.A. Miettinen T.A. Regulation of cholesterol synthesis and storage in fat cells.J. Lipid Res. 1975; 16: 211-223Abstract Full Text PDF PubMed Google Scholar, 5Acton S.L. Scherer P.E. Lodish H.F. Krieger M. Expression cloning of SR-BI, a CD36-related class B scavenger receptor.J. Biol. Chem. 1994; 269: 21003-21009Abstract Full Text PDF PubMed Google Scholar). TGs leave adipose tissue as NEFAs after TG lipolysis (6Young S.G. Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis.Genes Dev. 2013; 27: 459-484Crossref PubMed Scopus (243) Google Scholar), while cholesterol is removed from adipocytes via transporters such as ABCA1 and ABCG1 (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Howard A.D. Verghese P.B. Arrese E.L. Soulages J.L. Characterization of apoA-I-dependent lipid efflux from adipocytes and role of ABCA1.Mol. Cell. Biochem. 2010; 343: 115-124Crossref PubMed Scopus (13) Google Scholar). ABCA1 is responsible for the efflux of cholesterol to apoA1 and small HDL particles and is the rate-limiting protein in HDL production (9McNeish J. Aiello R.J. Guyot D. Turi T. Gabel C. C. J. lipoprotein and in mice with of PubMed Scopus Google Scholar, M. M. C. in in and lipoprotein PubMed Scopus Google Scholar). ABCA1 is N. R. and protein and of PubMed Scopus (243) Google Scholar), has been shown to a crucial of intracellular cholesterol and has an important role in the function of D. P. S. J. of ABCA1 cholesterol and influences and PubMed Scopus Google Scholar, J.S. ABCA1 influences insulin glucose homeostasis and to PubMed Scopus Google Scholar). of ABCA1 in the to changes in and function D. P. S. J. of ABCA1 cholesterol and influences and PubMed Scopus Google Scholar), ABCA1 in insulin of the of and in the ABCA1 PubMed Scopus Google Scholar). ABCA1 has been shown to and in adipocytes (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Howard A.D. Verghese P.B. Arrese E.L. Soulages J.L. Characterization of apoA-I-dependent lipid efflux from adipocytes and role of ABCA1.Mol. Cell. Biochem. 2010; 343: 115-124Crossref PubMed Scopus (13) Google Scholar). adipose tissue lacking ABCA1 has cholesterol efflux with increased cholesterol stores (9McNeish J. Aiello R.J. Guyot D. Turi T. Gabel C. C. J. lipoprotein and in mice with of PubMed Scopus Google Scholar, S. N. J.S. Adipose tissue to lipoprotein in PubMed Scopus Google Scholar), that cholesterol efflux is important in adipocyte cholesterol in adipocyte cholesterol homeostasis are associated with adipose dysfunction and obesity (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). However, the role of ABCA1 and intracellular cholesterol in adipose function with to body and glucose metabolism is cholesterol has been to a role in adipose tissue dysfunction (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). from increased stores of TGs and cholesterol (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). Furthermore, in of TG lipolysis has been shown to cholesterol efflux (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). it has been that cholesterol TG stores Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). also that ABCA1 to TG metabolism in adipocytes and adipose tissue Adipose tissue dysfunction is a of obesity M. Adipose tissue dysfunction in Clin. Endocrinol. PubMed Scopus Google and is an important for insulin glucose and the of M. Adipose tissue dysfunction in Clin. Endocrinol. PubMed Scopus Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar). Adipose tissue dysfunction glucose of NEFAs and adipokines in plasma (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar). from adipose tissue insulin and insulin Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar). Expression and of the various adipokines insulin sensitivity, insulin and glucose S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar). Adipocyte cholesterol also glucose homeostasis in the adipocyte. cholesterol from the adipocyte expression and adipocyte glucose in Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). for a cholesterol and adipocyte glucose homeostasis. that cholesterol in adipocytes have important for glucose homeostasis. ABCA1 has been shown to adipocyte cholesterol (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Howard A.D. Verghese P.B. Arrese E.L. Soulages J.L. Characterization of apoA-I-dependent lipid efflux from adipocytes and role of ABCA1.Mol. Cell. Biochem. 2010; 343: 115-124Crossref PubMed Scopus (13) Google Scholar). However, the role of ABCA1 in adipocyte function with to body and glucose metabolism is unknown. In we a the of cholesterol in adipocytes by ABCA1 with TG storage, body weight, and whole-body glucose homeostasis. lacking ABCA1 in the adipose tissue by ABCA1 mice with mice the the mice have been shown to in ABCA1 specifically in adipose S. N. J.S. Adipose tissue to lipoprotein in PubMed Scopus Google Scholar). on a and had to high-fat, high-cholesterol and mice used for To the role of adipocyte ABCA1 in mice fed an fat and cholesterol of in with by the of and in with after and in and adipose tissue was from the and adipose tissue from the was to the was the and was in a from after in was to was and the was and in TGs with TG and cholesterol with cholesterol tissue by and to a and the and glucose protein B and and and ABCA1 was with and and the lipolysis adipose tissue was and cultured in Adipose tissue was with in the was a and TG and by tissue was from mice from the after to glucose was with a glucose glucose to the was the TGs with TG NEFAs with and cholesterol with cholesterol HDL cholesterol was after of lipoproteins from plasma and HDL by expression and plasma of protein in Biol. 2008; PubMed Scopus Google Scholar). and with for to and with glucose in for glucose with insulin in for insulin was via the and and after and was for from mice with and the was with in via the was after and in and glucose in for by in in the was are as by significant ABCA1 protein expression in adipose tissue was by to the of ABCA1 in adipose tissue from ABCA1−ad/−ad significant in adipocyte ABCA1 protein in ABCA1−ad/−ad mice was observed To that ABCA1 to expression of the was to we also ABCA1 in and and in ABCA1 protein ABCA1 is a major of cholesterol efflux (9McNeish J. Aiello R.J. Guyot D. Turi T. Gabel C. C. J. lipoprotein and in mice with of PubMed Scopus Google Scholar, M. M. C. in in and lipoprotein PubMed Scopus Google Scholar), we of ABCA1 in adipocytes adipose cholesterol We observed a significant in the cholesterol in and in ABCA1−ad/−ad mice with mice on a an diet, we observed a significant of cholesterol in and in ABCA1−ad/−ad mice To intracellular cholesterol homeostasis, cholesterol has been shown to the expression of genes cholesterol metabolism via and the receptor Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar, N. P. receptors as of metabolic and Clin. PubMed Scopus Google Scholar). we the of adipocyte ABCA1 the expression of genes involved in maintaining cholesterol homeostasis. in expression as as a in expression and protein was observed ABCG1 is a cholesterol important in the of tissue cholesterol homeostasis by cholesterol efflux to HDL P. J. P.A. ABCG1 has a role in cholesterol efflux to HDL and lipid Metab. Full Text Full Text PDF PubMed Scopus Google Scholar). of cholesterol by J.L. of in plasma 1975; PubMed Scopus Google Scholar, J.L. Expression of the in mechanism for a in PubMed Scopus Google Scholar). Our that the of ABCA1 adipose tissue cholesterol homeostasis and that adipocytes for in lipid homeostasis by the expression of genes involved in cholesterol is associated with the of cholesterol and TGs in adipose tissue (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). We changes in adipocyte ABCA1 expression and cholesterol body weight, fat weight, and adipocyte TG a diet, ABCA1−ad/−ad mice demonstrated in body weight, fat weight, and adipose tissue TG with However, on an fat and of cholesterol ABCA1−ad/−ad mice To these changes in body in changes to adipose tissue we adipose tissue with increased body and showed a significant in To changes in TG we from of adipose tissue and observed that TG was increased in and for protein Our that of adipocyte ABCA1 to cholesterol accumulation, increased TG in enlarged fat pads, and increased body weight. Adipose tissue stores of as of energy and used to and However, in to the adipocyte plasma and the adipocyte TGs by a as lipolysis (6Young S.G. Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis.Genes Dev. 2013; 27: 459-484Crossref PubMed Scopus (243) Google Scholar). lipolysis has been shown to cholesterol efflux ABCA1 (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar). that an ABCA1 function and TG In to address we ABCA1 expression TG We lipolysis and observed in the from adipose tissue lacking ABCA1 that cholesterol efflux TG TG stores in adipose tissue are by the of TG TG and To possible adipocyte ABCA1 and TG homeostasis, we the expression of major genes in TG significant was observed in expression is a crucial involved in TG S.L. S. synthesis and lipid of to the Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). However, the of increased on TG metabolism is because protein of In adipose dysfunction is associated with including plasma TG and HDL Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, R. and Clin. Full Text Full Text PDF PubMed Scopus Google Scholar). In to the of adipocyte ABCA1 to plasma lipid metabolism, we and NEFAs in the plasma of and ABCA1−ad/−ad We decreased plasma cholesterol because of decreased efflux of cholesterol from adipose tissue in ABCA1−ad/−ad We observed a in plasma cholesterol plasma of HDL cholesterol showed significant was a significant in plasma TG in ABCA1−ad/−ad mice in adipose ABCA1 was from the after and for the are are in a was from the after and for the are are and adipose dysfunction have on plasma also have been associated with P. J. PubMed Scopus Google Scholar). the mechanism by adipose tissue lipid in the increased decreased and and insulin a role (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar, R. and Clin. Full Text Full Text PDF PubMed Scopus Google Scholar). To the of adipose ABCA1 on the we and lipid in ABCA1−ad/−ad an diet, ABCA1−ad/−ad mice had an increased and demonstrated of TG and cholesterol in tissue Adipose tissue is in whole-body glucose homeostasis the of adipokines such as adiponectin, and (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar). on various including the to insulin and the to insulin are associated with insulin insulin and is an while with and to and energy (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar). and adipose dysfunction alter expression and secretion. We adipose tissue dysfunction to the of ABCA1 the expression of genes to whole-body glucose homeostasis. In adipose tissue, we that expression of was and expression and showed a changes in expression glucose is a protein crucial for glucose of adipocyte cholesterol by in expression and glucose Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). in adipose tissue has been shown to whole-body glucose T. of the insulin in and PubMed Scopus Google Scholar). We ABCA1 expression and protein in adipose and protein expression of in from ABCA1−ad/−ad mice changes in expression and expression that adipose tissue dysfunction as a of ABCA1 impact whole-body glucose and insulin We that adipose ABCA1 cholesterol and TG storage in adipocytes and adiponectin, and alterations in lipid homeostasis and expression are to impaired glucose and insulin (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar). on these we that adipocyte ABCA1 to glucose and insulin in vivo. To address this, we glucose in ABCA1−ad/−ad we observed that glucose was in mice lacking adipocyte ABCA1 on a ABCA1−ad/−ad mice had impaired glucose an To determine impaired glucose by a in insulin sensitivity, we the in plasma glucose after insulin significant of insulin was observed in ABCA1−ad/−ad mice We in insulin was of a for intracellular insulin to we by mice an insulin by tissue and that the was in from ABCA1−ad/−ad insulin was in adipose tissue In the the of and we changes in adipocyte ABCA1 specifically tissue insulin insulin in in increased insulin by the to for insulin D. M. J. G. of insulin and is with a in PubMed Scopus Google Scholar, of insulin and dysfunction to the pathophysiology of 2003; PubMed Google Scholar). production of insulin to and insulin D. M. J. G. of insulin and is with a in PubMed Scopus Google Scholar, of insulin and dysfunction to the pathophysiology of 2003; PubMed Google Scholar). is with because ABCA1−ad/−ad mice demonstrated decreased insulin in tissue and a significant in plasma insulin on an To function was from ABCA1−ad/−ad and mice and in with and insulin in the was We observed that insulin from was in from ABCA1−ad/−ad mice after Our the that function from an in insulin as a of insulin in that intracellular cholesterol homeostasis in adipocytes is by ABCA1 and is crucial for glucose tolerance, insulin sensitivity, and Adipose tissue contains one of the largest pools of cholesterol in the is the storage for and is crucial in energy metabolism S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar). in adipocyte cholesterol are associated with adipose dysfunction and and ABCA1 has been shown to cholesterol efflux from adipose tissue (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, J. Aiello R.J. Guyot D. Turi T. Gabel C. C. J. lipoprotein and in mice with of PubMed Scopus Google Scholar, S. N. J.S. Adipose tissue to lipoprotein in PubMed Scopus Google Scholar). Adipose tissue dysfunction is an important for the of glucose insulin and (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, R. and Clin. Full Text Full Text PDF PubMed Scopus Google a role for adipocyte cholesterol and ABCA1 in these that cholesterol crucial in adipocyte function in the adipocyte in mice (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, 4Kovanen P.T. Nikkilä E.A. Miettinen T.A. Regulation of cholesterol synthesis and storage in fat cells.J. Lipid Res. 1975; 16: 211-223Abstract Full Text PDF PubMed Google Scholar, Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In we adipocyte ABCA1 adipose lipid and adipose function a specifically lacking ABCA1 in adipocytes. In we demonstrated increased intracellular cholesterol in the adipose tissue of adipocyte with increased cholesterol we observed an of fat and an of TGs in the adipose tissue of ABCA1−ad/−ad mice on an changes in adipose tissue have significant metabolic because we demonstrated that ABCA1−ad/−ad mice with impaired glucose tolerance, insulin sensitivity, and lower insulin from vivo. ABCA1−ad/−ad we showed that cholesterol in adipose tissue in mice on a and an in cholesterol is a of cholesterol efflux from adipose intracellular cholesterol has a major impact on lipid metabolism because cholesterol the expression of genes involved in intracellular lipid homeostasis. increased intracellular cholesterol the expression of and the via to cholesterol synthesis and Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). In the of from intracellular cholesterol the the expression of cholesterol efflux genes including and Lay S. S. C. I. Le Liepvre X. R. P. Dugail I. a that glucose metabolism and expression in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, N. P. receptors as of metabolic and Clin. PubMed Scopus Google Scholar). In we observed decreased expression and an in expression in adipose We that the of ABCA1 cholesterol and influences various to cholesterol in adipocytes. ABCG1 to cholesterol efflux and decreased to cholesterol that are in the adipocyte to cholesterol homeostasis. has been that intracellular cholesterol influences TG stores in adipose tissue (3Yu B-L. Zhao S-P. Hu J-R. Cholesterol imbalance in adipocytes: a possible mechanism of adipocytes dysfunction in obesity.Obes. Rev. 2010; 11: 560-567Crossref PubMed Scopus (62) Google Scholar, I. Le Lay S. M. Le Liepvre X. Dagher G. P. adipocytes triglyceride cholesterol a Metab. Res. 2003; PubMed Scopus Google Scholar). is also by because we observed that adipose tissue TGs and cholesterol in to an has been shown in that increased cholesterol efflux from adipocytes the of TG lipolysis (7Le Lay S. Robichon C. Le Liepvre X. Dagher G. Ferre P. Dugail I. Regulation of ABCA1 expression and cholesterol efflux during adipose differentiation of 3T3–L1 cells.J. Lipid Res. 2003; 44: 1499-1507Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar, 8Howard A.D. Verghese P.B. Arrese E.L. Soulages J.L. Characterization of apoA-I-dependent lipid efflux from adipocytes and role of ABCA1.Mol. Cell. Biochem. 2010; 343: 115-124Crossref PubMed Scopus (13) Google Scholar). a possible ABCA1 and TG lipolysis in adipocytes. We demonstrated that TG lipolysis is in adipose tissue from ABCA1−ad/−ad that ABCA1 TG and TG lipolysis to the TG we observed in adipose tissue from ABCA1−ad/−ad mice on an We because we a in ABCA1−ad/−ad mice and ABCA1−ad/−ad mice demonstrated increased body weight, in glucose tolerance, and increased insulin on an that adipocyte ABCA1 is crucial for adipose tissue function in to fat and Our also that of adipocyte ABCA1 and in intracellular cholesterol are to whole-body glucose body and adipocyte TG are associated with adipocyte to a of metabolic including glucose insulin and M. Adipose tissue dysfunction in Clin. Endocrinol. PubMed Scopus Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar, of PubMed Scopus (67) Google Scholar). are by adipose tissue the of NEFAs and adipokines in plasma (1Rasouli N. Kern P.A. Adipocytokines and the metabolic complications of obesity.J. Clin. Endocrinol. Metab. 2008; 93: S64-S73Crossref PubMed Scopus (592) Google Scholar, 2Galic S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, S.L. R.J. adipocytes: fat J. Biochem. Biol. 44: PubMed Scopus Google Scholar). from adipose tissue to and has been shown to insulin and Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar). However, we in the plasma of ABCA1−ad/−ad Expression and of an with adipose S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar). of insulin and lipid S. Oakhill J.S. Steinberg G.R. Adipose tissue as an endocrine organ.Mol. Cell. Endocrinol. 2010; 316: 129-139Crossref PubMed Scopus (1239) Google Scholar, Adipocyte obesity to insulin and Rev. Biol. 2008; PubMed Scopus Google Scholar, P. J. PubMed Scopus Google Scholar). In ABCA1−ad/−ad we observed adiponectin, and a in and expression with increased In we observed a in adiponectin, is the of in plasma to the insulin and glucose as as the lipid accumulation, we observed in in adipose tissue has been shown to whole-body glucose and insulin is of T. of the insulin in and PubMed Scopus Google Scholar). that associated with a role in insulin In an to by adipocyte ABCA1 whole-body glucose we the expression of genes and involved in glucose metabolism in the We of in the Expression of the genes and glucose in the also We that the we observed in ABCA1−ad/−ad mice to glucose by glucose P. J. PubMed Scopus Google Scholar). When glucose to insulin the to by insulin secretion. However, insulin in dysfunction and of insulin and dysfunction to the pathophysiology of 2003; PubMed Google Scholar, D. in insulin and in the of 2010; PubMed Scopus Google Scholar, J. in in of for role of of 2003; PubMed Scopus Google Scholar). We observed that ABCA1 mice have increased insulin while insulin from in to glucose was We conclude that changes in adipose tissue to dysfunction as a of insulin in the of ABCA1−ad/−ad of mice specifically lacking ABCA1 in adipocytes has a to the role of adipocyte ABCA1 in glucose and lipid metabolism in vivo. Our a role for adipocyte intracellular cholesterol by ABCA1 in the adipocyte in whole-body glucose homeostasis. Our that adipocyte ABCA1 adipocyte cholesterol and TG stores and influences insulin and glucose We conclude that ABCA1 in the adipocyte is an important of intracellular lipid stores and has significant on glucose for and of for and for and of for of the and and S. for with protein B adipose tissue adipose tissue glucose high-fat, high-cholesterol LDL receptor adipose tissue adipose tissue protein

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