Fatty acid metabolism in adipocytes: functional analysis of fatty acid transport proteins 1 and 4

The role of fatty acid transport protein 1 (FATP1) and FATP4 in facilitating adipocyte fatty acid metabolism was investigated using stable FATP1 or FATP4 knockdown (kd) 3T3-L1 cell lines derived from retrovirus-delivered short hairpin RNA (shRNA). Decreased expression of FATP1 or FATP4 did not affect preadipocyte differentiation or the expression of FATP1 (in FATP4 kd), FATP4 (in FATP1 kd), fatty acid translocase, acyl-coenzyme A synthetase 1, and adipocyte fatty acid binding protein but did lead to increased levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α. Both FATP1 and FATP4 kd adipocytes exhibited reduced triacylglycerol deposition and corresponding reductions in diacylglycerol and monoacylglycerol levels compared with control cells. FATP1 kd adipocytes displayed an ∼25% reduction in basal 3H-labeled fatty acid uptake and a complete loss of insulin-stimulated 3H-labeled fatty acid uptake compared with control adipocytes. In contrast, FATP4 kd adipocytes as well as HEK-293 cells overexpressing FATP4 did not display any changes in fatty acid influx. FATP4 kd cells exhibited increased basal lipolysis, whereas FATP1 kd cells exhibited no change in lipolytic capacity. Consistent with reduced triacylglycerol accumulation, FATP1 and FATP4 kd adipocytes exhibited enhanced 2-deoxyglucose uptake compared with control adipocytes. These findings define unique and distinct roles for FATP1 and FATP4 in adipose fatty acid metabolism. The role of fatty acid transport protein 1 (FATP1) and FATP4 in facilitating adipocyte fatty acid metabolism was investigated using stable FATP1 or FATP4 knockdown (kd) 3T3-L1 cell lines derived from retrovirus-delivered short hairpin RNA (shRNA). Decreased expression of FATP1 or FATP4 did not affect preadipocyte differentiation or the expression of FATP1 (in FATP4 kd), FATP4 (in FATP1 kd), fatty acid translocase, acyl-coenzyme A synthetase 1, and adipocyte fatty acid binding protein but did lead to increased levels of peroxisome proliferator-activated receptor γ and CCAAT/enhancer binding protein α. Both FATP1 and FATP4 kd adipocytes exhibited reduced triacylglycerol deposition and corresponding reductions in diacylglycerol and monoacylglycerol levels compared with control cells. FATP1 kd adipocytes displayed an ∼25% reduction in basal 3H-labeled fatty acid uptake and a complete loss of insulin-stimulated 3H-labeled fatty acid uptake compared with control adipocytes. In contrast, FATP4 kd adipocytes as well as HEK-293 cells overexpressing FATP4 did not display any changes in fatty acid influx. FATP4 kd cells exhibited increased basal lipolysis, whereas FATP1 kd cells exhibited no change in lipolytic capacity. Consistent with reduced triacylglycerol accumulation, FATP1 and FATP4 kd adipocytes exhibited enhanced 2-deoxyglucose uptake compared with control adipocytes. These findings define unique and distinct roles for FATP1 and FATP4 in adipose fatty acid metabolism. Dysregulation in adipose fatty acid metabolism is a significant contributing factor to the development of obesity and associated metabolic diseases, such as type 2 diabetes, hypertension, and cardiovascular disease (1Frayn K.N. Obesity and metabolic disease: is adipose tissue the culprit? Proc. Nutr. Soc. 2005; 64: 7-13Google Scholar, 2Lazar M.A. How obesity causes diabetes: not a tall tale. Science. 2005; 307: 373-375Google Scholar, 3Zhang J. Fu M. Cui T. Xiong C. Xu K. Zhong W. Xiao Y. Floyd D. Liang J. Li E. Selective disruption of PPARgamma 2 impairs the development of adipose tissue and insulin sensitivity. Proc. Natl. Acad. Sci. USA. 2004; 101 (et al.): 10703-10708Google Scholar). Central to this imbalance are differing rates of long-chain fatty acid (LCFA) influx, efflux, and metabolism by adipose tissue. Although appreciated for decades, the molecular mechanisms that control and mediate fatty acid flux in fat cells remain poorly defined from structural, mechanistic, and regulatory viewpoints. Although diffusion may play a fundamental role in the transbilayer movement of LCFA, molecular and genetic evidence from loss- or gain-of-function studies have identified a number of proteins facilitating some component of the fatty acid influx process (4Coburn C.T. Knapp Jr., F.F. Febbraio M. Beets A.L. Silverstein R.L. Abumrad N.A. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J. Biol. Chem. 2000; 275: 32523-32529Google Scholar, 5Stahl A. Evans J.G. Pattel S. Hirsch D. Lodish H.F. Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Dev. Cell. 2002; 2: 477-488Google Scholar, 6Richards M.R. Harp J.D. Ory D.S. Schaffer J.E. Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes. J. Lipid Res. 2006; 47: 665-672Google Scholar, 7Zhou S.L. Stump D. Kiang C.L. Isola L.M. Berk P.D. Mitochondrial aspartate aminotransferase expressed on the surface of 3T3-L1 adipocytes mediates saturable fatty acid uptake. Proc. Soc. Exp. Biol. Med. 1995; 208: 263-270Google Scholar, 8Trigatti B.L. Anderson R.G. Gerber G.E. Identification of caveolin-1 as a fatty acid binding protein. Biochem. Biophys. Res. Commun. 1999; 255: 34-39Crossref PubMed Scopus (176) Google Scholar). Proteins implicated in fatty acid uptake are fatty acid translocase (CD36), acyl-CoA synthetases fatty acid transport protein (FATP) and acyl-coenzyme A synthetase (ACSL) family members, plasma membrane fatty acid binding protein, and caveolin-1. The relative contribution of each polypeptide to overall cellular fatty acid influx has not been quantitatively evaluated. FATPs are a family of membrane-bound proteins that catalyze the ATP-dependent esterificaton of LCFAs and very LCFAs to their acyl-CoA derivatives (9Hall A.M. Smith A.J. Bernlohr D.A. Characterization of the acyl-CoA synthetase activity of purified murine fatty acid transport protein 1. J. Biol. Chem. 2003; 278: 43008-43013Google Scholar). The FATPs bear 20–40% sequence identity to the long-chain ACSL class of proteins that function in long-chain acyl-CoA production. In mammals, six different isoforms of FATP (FATP1 to FATP6) have been identified with tissue-specific expression patterns (10Stahl A. A current review of fatty acid transport proteins (SLC27). Pflugers Arch. 2004; 447: 722-727Crossref PubMed Scopus (225) Google Scholar). White adipose tissue predominantly expresses FATP1, FATP4, and ACSL1, whereas brown adipose tissue additionally expresses ACSL5. FATP1 is a 63 kDa protein localized primarily to high-density membranes and to a lesser extent in the plasma and low-density membrane fractions of murine adipocytes and 3T3-L1 cells (5Stahl A. Evans J.G. Pattel S. Hirsch D. Lodish H.F. Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Dev. Cell. 2002; 2: 477-488Google Scholar). FATP1 (as well as ACSL1) was identified using an expression clone strategy designed to identify proteins that enhanced LCFA uptake (11Schaffer J.E. Lodish H.F. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell. 1994; 79: 427-436Google Scholar). Evidence for the role of FATPs in fatty acid transport has been qualitatively evaluated by various loss-of-function/gain-of-function model HEK-293 cell lines overexpressing murine FATP1 increased LCFA uptake and triacylglycerol Smith A.J. Xu A.M. Bernlohr D.A. FATP1 and and metabolism in cells. J. Lipid Res. 2002; Scholar). A model with expression of FATP1 increased LCFA uptake A. M. S. Xu expression of fatty acid transport protein 1 in the causes Res. 2005; (et al.): Scholar). of the FATP1 expressed in LCFA uptake A. J. of the to the murine fatty acid transport protein impairs uptake and on long-chain fatty J. Biol. Chem. and a murine FATP1 knockout exhibited reduced muscle acyl-CoA levels and increased insulin T. S. R.L. A. Hirsch of fatty acid transport protein 1 insulin in J. 2004; (et al.): Scholar). FATP4 is the of FATP1 that is expressed in adipose tissue T. A.M. Bernlohr D.A. W. fatty acid transport protein characterization of the and as a very long chain acyl-CoA Scholar). role in adipose tissue metabolism is FATP4 is expressed in and and is the fatty acid in the localized to the of is to mediate the uptake of fatty acids A. Hirsch S. S. M. A. Identification of the fatty acid transport protein. Cell. 1999; (et al.): Scholar). FATP4 displayed of a that has been associated with a function in the Hirsch S. Y. A.M. T. A. Lodish H.F. A. of fatty acid transport in J. Biol. Chem. 2003; 278: Scholar, T. W. with disruption of the fatty acid transport protein of J. Biol. 2003; (et al.): Scholar, C.L. Schaffer J.E. of a roles for fatty acid transport protein in and Proc. Natl. Acad. Sci. USA. 2003; Scholar). FATP4 an ACSL with to very LCFAs that may for the of in the of a A.M. T. W. Bernlohr D.A. of purified murine fatty acid transport protein and of acyl-CoA synthetase in tissues from FATP4 mice. J. Biol. Chem. 2005; Scholar, T. D. W. in with J. 2005; Google Scholar). in the FATP4 have identified this as a for the insulin K. M. S. A. M. and of fatty acid transport in to of the insulin J. 2004; Scholar). FATP4 expression levels with of obesity and insulin K. J. A. A. Expression of proteins in adipose tissue in to obesity and insulin 2004; 47: Scholar). These the of the of FATP4 function in adipocyte fatty acid uptake and metabolism. is to identify and define in the mechanisms LCFA flux in cells and the roles of proteins implicated in the influx In this evaluated the of FATP1 and FATP4 in LCFA influx and using knockdown 3T3-L1 adipocytes using of short hairpin RNA FATP1 or that FATP1 the insulin-stimulated component of LCFA uptake but has a role in basal LCFA uptake in 3T3-L1 adipocytes. FATP4 not play a role in basal or insulin-stimulated fatty acid uptake. FATP4 kd adipocytes exhibited increased basal lipolysis, a role in fatty acid in 3T3-L1 adipocytes. from and from was from fatty acids from acid and acid from and from as proliferator-activated receptor γ and binding protein from from from of from and from of and from 3T3-L1 and adipocytes as of fatty acid synthetase in 3T3-L1 J. Biol. Chem. 255: Scholar). in cells to in with and of and from the whereas insulin was adipocytes in and The RNA by the was for FATP1 kd in 3T3-L1 cells. was to expresses the control of the RNA of the in cells D. D.S. stable by in cells. 2003; (et al.): Scholar). in a FATP1 and FATP4 and the in sequence for each and on the of the to the expression of by or in cells with a expression and each of the of the sequence was for the of The the FATP1 sequence was and that the FATP4 sequence was A a FATP1 sequence was as a in cells and and (4Coburn C.T. Knapp Jr., F.F. Febbraio M. Beets A.L. Silverstein R.L. Abumrad N.A. Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. J. Biol. Chem. 2000; 275: 32523-32529Google Scholar). 3T3-L1 with the for in the of a of of to for the of 2 kd cell lines from a of 3T3-L1 FATP4 or control was and HEK-293 cells by HEK-293 cells are an model to FATP4 function in metabolism are a cell in and have been to FATP expression Smith A.J. Xu A.M. Bernlohr D.A. FATP1 and and metabolism in cells. J. Lipid Res. 2002; Scholar). of the cells in and and was with the of using cloning and lines lines for FATP4 The cell lines and control cells in cell lines for cellular synthetase and uptake by a to that for 3T3-L1 adipocytes. 3T3-L1 adipocytes in a 1 1 and and cell of by on a and to or The membranes with in and for 1 with the membranes with to was by and protein was by using a 3T3-L1 adipocytes for in and of fatty acids 3H-labeled fatty acids to the with or insulin for and fatty acid uptake was by cells in and or each to fatty in a to a fatty acid of The for the different fatty acids in the using LCFA binding for as by and A. A.M. of long-chain fatty acids and of fatty acid levels using the Scholar). the cells in and The cells in for and the fatty acids by cellular influx of fatty fatty using The was in a of and to The various and of the by using the by M.A. of in and using J. Lipid Res. and by and monoacylglycerol by the by and of using the Fatty acids using a in and and for ACSL activity by the of or acid to their derivatives by a from K. S. M. Y. A synthetase from characterization and with A synthetase activity and Biophys. as by and Bernlohr (9Hall A.M. Smith A.J. Bernlohr D.A. Characterization of the acyl-CoA synthetase activity of purified murine fatty acid transport protein 1. J. Biol. Chem. 2003; 278: 43008-43013Google Scholar). for 2 and in of a fatty acid to and with the of of of and of to The was with of to fatty and the was by 3T3-L1 cells on and as the cells of and in for 2 Insulin was and the cells in and in for the cells in and for 2 in and The cells in a of or or in a of in the for 1 in a of in with the in with for and by using a to a with a and to the and using and using uptake in 3T3-L1 adipocytes was as M. Insulin by Proc. Natl. Acad. Sci. USA. 2003; Scholar). cells in with and 2 and with or insulin for uptake was by the of to a of 2-deoxyglucose uptake was by with and the cells with of The was by 2-deoxyglucose uptake was in the of and from the uptake to uptake. the role of FATP1 and FATP4 in fatty acid metabolism in stable 3T3-L1 adipocyte FATP1 kd and FATP4 kd cell lines derived from protein. kd a and using the and insulin complete loss of FATP1 expression was in cells FATP1 (FATP1 kd), that the protein is not for adipose Expression of FATP4 a cell of the control FATP4 1 of protein from FATP1 FATP4 and control cells an in the expression of and an in protein. the in expression of the expression of proteins by and implicated in some of fatty acid influx ACSL1, the adipocyte fatty acid binding protein and FATP in in cell lines Both FATP1 kd and FATP4 kd adipocytes exhibited reduced of of triacylglycerol was reduced in FATP1 kd and FATP4 kd 3T3-L1 adipocytes relative to the control was not different from or not Consistent with the reduced FATP1 kd and FATP4 kd cells exhibited and monoacylglycerol FATP4 kd but not FATP1 kd exhibited a in fatty acid 2 FATP1 is an ACSL with but a relative to fatty acid FATP4 has a ACSL relative to FATP1 and and has a for very long-chain long-chain fatty acids A.M. T. W. Bernlohr D.A. of purified murine fatty acid transport protein and of acyl-CoA synthetase in tissues from FATP4 mice. J. Biol. Chem. 2005; Scholar). the of FATP1 kd and FATP4 kd on cellular ACSL and for fatty acid using a of fatty acid in 1, kd of FATP1 in an in cellular and activity but no change in cellular ACSL with FATP1 kd FATP4 kd adipocytes displayed a in cellular and ACSL and no change in cellular The in ACSL activity for kd cell well with the in and monoacylglycerol levels in the cell of ACSL of cellular from 3T3-L1 adipocytes FATP1 and FATP4 compared with the with control with control with control with control with control with control acyl-coenzyme A FATP1, fatty acid transport protein ACSL of cell from 3T3-L1 adipocytes for of acid acid acid and acid and are expressed as protein. are of with control in a acyl-coenzyme A FATP1, fatty acid transport protein ACSL of cell from 3T3-L1 adipocytes for of acid acid acid and acid and are expressed as protein. are of was a in cellular ACSL as well as triacylglycerol the role that FATP1 and FATP4 may play in fatty acid uptake. and (5Stahl A. Evans J.G. Pattel S. Hirsch D. Lodish H.F. Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Dev. Cell. 2002; 2: 477-488Google have that insulin the translocation of FATP1 from to the plasma 3T3-L1 adipocytes and with or insulin for and the expression of FATP1, FATP4, and was evaluated using in the of to the plasma as did some FATP1 to In to FATP1 and FATP4 did not to localized to the plasma membrane basal and did not to the plasma membrane in the of the translocation studies for FATP1 and FATP4 with the cellular influx of 3H-labeled fatty acids of different chain was evaluated basal and insulin-stimulated in basal compared with control FATP1 kd adipocytes displayed an ∼25% in fatty acid uptake for and of influx studies with not control 3T3-L1 insulin to an in fatty acid influx for and The in and acid uptake in to insulin was in FATP1 kd a role of FATP1 in insulin-stimulated fatty acid influx. is with the translocation of FATP1 to the plasma membrane in to insulin and is of the role of FATP1 in fatty acid uptake as a function of cellular The in acid uptake with insulin in FATP1 kd cells is not but is by compared with the of control cells to that in to FATP1, ACSL with for acid may cellular uptake. FATP4 the ACSL rates relative to cellular such as FATP1 and ACSL1, FATP4 kd adipocytes did not any change in or acid uptake relative to the control cells basal and insulin-stimulated is in with the of fatty acid influx studies with different stable HEK-293 cell lines of FATP4 The of FATP4 expressed by each cell was by and and as FATP4 in the ACSL activity for a fatty acid with cell from different HEK-293 cell lines to the of FATP4 the expression levels of FATP4 in HEK-293 cells did not affect the of cellular fatty acid influx for acid FATP1, FATP4 is not to the plasma membrane in to insulin and is not for basal or insulin-stimulated fatty acid uptake. the of fatty acid influx in FATP1 kd and FATP4 kd adipocytes with of fatty acid efflux, FATP1 and FATP4 kd adipocytes evaluated for their to basal and was as the of and fatty acids from cells as a of in and fatty acid in FATP1 and FATP4 kd adipocytes exhibited no significant cell Consistent with the FATP1 kd adipocytes exhibited reduced basal fatty acid In contrast, FATP4 kd adipocytes exhibited an in and an in fatty acid basal Insulin the translocation of FATP1 to the plasma with the in fatty acid uptake in control adipocytes that was in FATP1 kd adipocytes. to FATP1, FATP4 localized to membranes with insulin and did not affect fatty acid uptake. the unique roles of fatty acid in the in the metabolism of various cellular influx in FATP1 FATP4 and control adipocytes basal and in basal and insulin-stimulated the of the fatty acid is to and primarily A very of fatty acids are of FATP1 kd and control adipocytes that was an in fatty acid uptake in the FATP1 kd adipocytes basal was a in the insulin-stimulated of uptake. A corresponding in fatty acyl-CoA levels and triacylglycerol was in FATP1 kd adipocytes compared with the These are with a for FATP1 in the insulin-stimulated component of LCFA influx and triacylglycerol in 3T3-L1 adipocytes. Although FATP4 did not play a role in fatty acid uptake basal an in the fatty acyl-CoA was in FATP4 kd adipocytes relative to the control The for this is but may that proteins may for LCFA influx but that FATP4 a role in insulin no change was in fatty acyl-CoA levels or in any class in FATP1 kd and 3T3-L1 adipocytes in a in FATP4 kd and 3T3-L1 adipocytes in a FATP1 kd and FATP4 kd adipocytes reduced compared with the control and reduced triacylglycerol deposition is with increased uptake T. J. Y. K. Y. T. K. The insulin associated with and Med. (et al.): Scholar, M. K. M. W. D. of on adipose tissue the of obesity and insulin evaluated the loss of each FATP on basal and insulin-stimulated 2-deoxyglucose uptake. was an in basal and insulin-stimulated uptake in FATP1 kd adipocytes compared with the control The in uptake insulin was the in adipocyte cell control and FATP4 kd cells evaluated for 2-deoxyglucose cells FATP4 exhibited an in insulin-stimulated uptake but no change in basal uptake. in FATP1 has been investigated for role in fatty acid transport and and a knockout model have implicated FATP1 in fatty acid uptake A. M. S. Xu expression of fatty acid transport protein 1 in the causes Res. 2005; (et al.): Scholar, T. S. R.L. A. Hirsch of fatty acid transport protein 1 insulin in J. 2004; (et al.): Scholar). FATP1 is by by insulin and by a Smith A.J. Schaffer J.E. Bernlohr D.A. Characterization of the murine fatty acid transport protein and insulin J. Biol. Chem. Scholar, Bernlohr D.A. Identification of a peroxisome in the murine fatty acid transport protein J. Biol. Chem. 1999; Scholar). Consistent with FATP1 expression in muscle and fat is increased in and for FATP1 reduced muscle LCFA uptake and to insulin T. S. R.L. A. Hirsch of fatty acid transport protein 1 insulin in J. 2004; (et al.): Scholar, P.D. S.L. Kiang C.L. Stump D. M. Isola L.M. of long chain fatty acids is in adipocytes of with genetic obesity and J. Biol. Chem. Scholar). In fat a the expression of CD36 and FATP1, that the of this may the of adipose LCFA influx S.L. A. J. of on fatty acid uptake in adipose and in muscle tissues of J. Lipid Res. 2005; Scholar). the of a role for FATP1 in fatty acid influx may to the of the of this class of Although loss- and gain-of-function model have defined a role of FATP4 as a fatty acid and in the of the role in adipocyte fatty acid uptake and metabolism is well FATP4 expression in is by and receptor M. Y. proliferator-activated and receptor fatty acid uptake by J. 2005; Scholar). in a role of FATP4 in insulin K. M. S. A. M. and of fatty acid transport in to of the insulin J. 2004; Scholar). for a of exhibited fatty acids and reduced and insulin FATP4 expression levels with obesity that is of genetic K. J. A. A. Expression of proteins in adipose tissue in to obesity and insulin 2004; 47: Scholar). a kd in the protein expression levels in 3T3-L1 adipocytes loss of FATP1 and FATP4 to an in the expression of and The for this is not but may to reduced of the as to changes in S. E. of the peroxisome proliferator-activated receptor is to J. Biol. Chem. 2000; 275: Scholar). the increased expression of not increased in ACSL1, and of FATP1 or FATP4 in 3T3-L1 adipocytes to changes in cellular long-chain ACSL any change in cellular very long-chain ACSL of FATP1 expression in an loss in insulin-stimulated and acid uptake and an in insulin-stimulated acid influx. reduction in FATP1 expression a ∼25% in basal LCFA influx for fatty acids of FATP4, on the did not affect basal or insulin-stimulated fatty acid and of FATP4 in HEK-293 cells did not affect cellular fatty acid influx and (5Stahl A. Evans J.G. Pattel S. Hirsch D. Lodish H.F. Insulin causes fatty acid transport protein translocation and enhanced fatty acid uptake in adipocytes. Dev. Cell. 2002; 2: 477-488Google have that in 3T3-L1 insulin the translocation of FATP1 from membranes to the plasma as to a to of FATP1 the in the relative of the the plasma membrane with increased LCFA influx and may to of the fatty acid transport function of with FATP4 kd adipocytes that FATP4 has a ACSL relative to FATP1 and ACSL1, is localized to membranes and not the plasma the not to insulin-stimulated or basal fatty acid uptake. In to FATP4 in cells was localized to the did in a in LCFA influx K. T. C. D. J. W. J. uptake of fatty acids by the acyl-CoA synthetase J. Sci. 2006; Scholar). is not findings are the of in the of FATP4 in or a in the cell not the of proteins in insulin-stimulated LCFA influx. insulin-stimulated acid uptake is not in FATP1 kd that ACSL in insulin-stimulated acid fatty acid influx. ACSL1, has been to a with FATP1 M.R. Harp J.D. Ory D.S. Schaffer J.E. Fatty acid transport protein 1 and long-chain acyl coenzyme A synthetase 1 interact in adipocytes. J. Lipid Res. 2006; 47: 665-672Google in some of insulin-stimulated or basal LCFA influx. is not in this is basal LCFA influx in adipocytes. Insulin of LCFA influx is fatty and is quantitatively relative to insulin-stimulated uptake to ACSL1) are to basal LCFA influx. Fatty acid the adipocyte by of basal lipolysis, the of from the adipocyte Y. and the acid J. Biol. Chem. 2003; 278: PubMed Scopus Google Scholar). The basal lipolytic is to triacylglycerol and in fat cells have rates of basal fat cells S. D. S. of in fat cells of J. Google Scholar). the and the in basal are well that basal lipolytic FATP4 kd adipocytes exhibited an in the of and fatty acid relative to a control cell for this is that the ACSL activity of FATP4 may some component of the of fatty acids derived from basal of the triacylglycerol such as ACSL1, has been to associated with the may play a role in fatty acid basal of proteins associated with of basal and 3T3-L1 adipocytes. J. Biol. Chem. 2004; Scholar). the of various that in 3T3-L1 the of fatty acids are to their acyl-CoA derivatives and the triacylglycerol In FATP1 kd a in LCFA influx was with reduced acyl-CoA levels as well as and monoacylglycerol the LCFA was not increased but with the model that the ACSL activity of FATP1 is for facilitating LCFA influx. These are in with the of and Schaffer Schaffer J.E. of for in the murine fatty acid transport protein long chain fatty acid J. Biol. Chem. have that of FATP1 to not reduced the activity of the but LCFA influx, that is to uptake. In to FATP1 kd FATP4 kd adipocytes no change in basal or insulin-stimulated cellular fatty acid influx. basal FATP4 kd adipocytes a in the of acyl-CoA but not The for this is but that basal FATP4 in LCFA but that proteins may mediate the in insulin no changes in the fatty acyl-CoA with the of the insulin and the role of FATP4 in basal and A. J. is in a of in adipocytes. J. Biol. Chem. 2005; that the of fatty acids to on or the plasma membrane of adipocytes. are with this and that acyl-CoA the plasma membrane may to triacylglycerol some type of Both FATP1 kd and FATP4 kd adipocytes exhibited increased insulin-stimulated uptake. FATP1 knockout a in insulin-stimulated uptake in muscle compared with A.M. A. FATP1 is an fatty acid in Cell. Biol. 2006; Scholar). Although the in uptake may quantitatively changes in uptake have metabolic insulin such as that in FATP1 knockout and the or of the FATP4 In FATP1 kd and FATP4 kd the of the of fatty acids on insulin and and diacylglycerol in 3T3-L1 adipocytes and Arch. Biochem. Biophys. 2003; of insulin is the development of kd adipocytes may an to identify that from triacylglycerol levels that affect insulin in adipocytes. In FATP1 and FATP4 ACSL and sequence each has unique roles in the FATP1 a role in basal fatty acid and by of translocation to the plasma membrane from membranes in to a role in insulin-stimulated fatty acid uptake. FATP4 is an ACSL that not play a role in basal or insulin-stimulated fatty acid uptake and may in fatty acid FATP1 and FATP4, by of their cellular and affect and of have been implicated in the development of obesity and insulin The for on the of FATP1 and FATP4 RNA was by of and the Obesity acyl-coenzyme A synthetase 1 adipocyte fatty acid binding protein fatty acid translocase CCAAT/enhancer binding protein fatty acid transport protein 1 knockdown long-chain fatty acid peroxisome proliferator-activated receptor γ RNA short hairpin RNA