Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells

Fatty acid binding proteins (FAB2222251) are low-molecular-mass, soluble, intracellular lipid carriers. Previous studies on adipocytes from adipocyte fatty acid binding protein (A-FABP)-deficient mice have revealed that both basal and isoproterenol-stimulated lipolysis were markedly reduced (Coe et al. 1999. J. Lipid Res. 40: 967–972). Herein, we report the construction of transgenic mice overexpressing the FABP5 gene encoding the epithelial fatty acid binding protein (E-FABP) in adipocytes, thereby allowing evaluation of the effects on lipolysis of increased FABP levels and of type specificity. In adipocytes from FABP5 transgenic mice, the total FABP protein level in the adipocyte was increased to 150% to the type to in the level of and of the were in and FABP5 transgenic both basal and lipolysis increased in adipocytes from the FABP5 transgenic of the fatty acid from the intracellular that from the adipocyte was that lipolysis and the total level of FABP lipolysis and FABP Fatty acid binding proteins (FAB2222251) are low-molecular-mass, soluble, intracellular lipid carriers. Previous studies on adipocytes from adipocyte fatty acid binding protein (A-FABP)-deficient mice have revealed that both basal and isoproterenol-stimulated lipolysis were markedly reduced (Coe et al. 1999. J. Lipid Res. 40: 967–972). Herein, we report the construction of transgenic mice overexpressing the FABP5 gene encoding the epithelial fatty acid binding protein (E-FABP) in adipocytes, thereby allowing evaluation of the effects on lipolysis of increased FABP levels and of type specificity. In adipocytes from FABP5 transgenic mice, the total FABP protein level in the adipocyte was increased to 150% to the type to in the level of and of the were in and FABP5 transgenic both basal and lipolysis increased in adipocytes from the FABP5 transgenic of the fatty acid from the intracellular that from the adipocyte was that lipolysis and the total level of FABP lipolysis and FABP fatty acid binding proteins are from in lipid and of intracellular fatty proteins and fatty and Lipid Res. of the have of the that the the J. fatty acid the the FABP of proteins in and binding of fatty and in have have to intracellular of fatty and and of intracellular fatty fatty and Lipid Res. fatty protein and Fatty acid in the in lipid and the of of and fatty in of and lipid of and adipocytes in to and in the of the proteins in thereby and of the adipocyte J. and of the of and from adipocyte to J. from the FABP are in the adipocyte fatty acid binding protein FABP5 epithelial fatty acid binding protein In the to that of in the adipocyte of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: the protein proteins fatty and of protein intracellular in of gene in fatty and of the intracellular lipid binding proteins of In to in adipocytes, in and of epithelial and fatty protein and Fatty acid binding protein in of the Res. protein in J. of and of in of the and fatty acid binding proteins acid in the of Res. Res. of of have the of to in FABP fatty protein and reduced in J. the fatty acid binding protein in fatty acid J. fatty acid from mice the fatty acid binding protein Res. mice reduced basal isoproterenol-stimulated lipolysis in and in the protein in fatty acid from the adipocyte of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: reduced in to and of the of adipocyte protein of adipocyte the of the FABP5 gene in adipocytes, in reduced total FABP level in FABP to of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: of from in the adipocyte fatty acid binding the reduced lipolysis in mice to the of the the of the in the total FABP the levels of of the the type of FABP to transgenic was that the FABP5 gene in the adipocyte the Herein, we report that increased total FABP level of to increased level of and in the level of in of from FABP5 transgenic mice increased basal and isoproterenol-stimulated that lipolysis to total FABP and to FABP acid and were from Fatty acid were from were from was from fatty acid was from mice, and FABP5 transgenic mice were mice were of and were on to in the mice were and were to of the were to were and the of and transgenic FABP5 gene and of the protein from the the was of the of of gene the and was to of the the FABP5 FABP5 gene was the the of in of of gene the were and of the to the and was and were in the of were of total and FABP5 to from FABP5 transgenic the FABP5 transgenic were and of to that and was levels of were in and to of protein were of and in proteins were to and and in were and and was the was on and FABP was from the protein the of the of from to mice were and in and and to were adipocytes were and in and in of the was and was to and fatty were of in were to was and the was were and to the lipid was of lipid in and Lipid Res. the were the and to the and acid to the that of the were in the total were from the in the were and was and the were and lipid were acid were in Fatty acid were and was fatty acid were of to of fatty acid was to the total the of adipocyte were in of in and was the of was the of to the adipocytes from the total fatty was the from of mice in of adipocyte fatty acid were in and acid were was of acid to the in acid of were and in were the of on to the fatty from the were and and the of acid in the was are was the are the that fatty acid transgenic was that levels of FABP5 in the FABP5 gene the adipocyte of the FABP5 gene and of the was the on the were to mice, and were the to type of the in the were and of to of was from the FABP5 gene to the that of the FABP5 transgenic mice in in of the adipocytes from the FABP5 transgenic mice were the were on from and of and FABP5 transgenic FABP adipocyte fatty acid binding epithelial fatty acid binding was and to the of Fatty acid binding protein levels were and the were to of was were on from of to FABP5 transgenic mice to in were on adipocyte protein to the was FABP5 in adipocytes levels of and were to of protein protein and both in In adipocytes, levels are protein levels are to total FABP level of protein and of In the adipocytes from FABP5 transgenic levels were to protein levels were to to 150% in FABP and of in to the mice, adipocyte FABP levels of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: the fatty acid binding and of and are are proteins and and of protein intracellular in and of the intracellular lipid binding proteins of the of in the FABP5 transgenic mice the of intracellular of and was on from the of and FABP5 transgenic the fatty were and from to fatty were and to and that to of the total fatty in the of intracellular fatty were the that in from to the of the total intracellular fatty acid in and FABP5 transgenic were to and was of mice are was were in the of the was in FABP5 transgenic to were and the fatty and of were the were in the of the levels in of in and FABP5 transgenic was and were fatty acid was on mice from are in adipocyte to Previous on adipocytes from the mice in basal and isoproterenol-stimulated the total FABP the and the of adipocytes from and FABP5 transgenic mice were in the of and the in the were in basal of was in the FABP5 transgenic mice to the in lipolysis was in to the of both to to the basal in in lipolysis in the FABP5 transgenic to the adipocytes both basal and lipolysis are in the FABP5 transgenic the levels of lipolysis are in the FABP5 transgenic adipocytes, that the of in the in lipolysis to the total levels of FABP the acid of adipocytes from and FABP5 transgenic Fatty acid was from adipocytes in basal of were in adipocytes from of mice from and were are of the of fatty lipolysis of revealed fatty the of were fatty and were the the of fatty the of fatty isoproterenol-stimulated lipolysis was to the of the of intracellular the of fatty isoproterenol-stimulated lipolysis in mice in of from isoproterenol-stimulated adipocytes from and FABP5 transgenic were to and of the total was of mice are was were in the of in adipocyte lipid the to fatty was adipocytes were and acid that was in the to fatty in the FABP5 transgenic adipocytes to the type the adipocytes the acid in the to the in the of acid levels of in the FABP5 studies are to to FABP levels in adipocytes in in the level of fatty acid in acid in adipocytes from and FABP5 transgenic was acid and FABP5 were in adipocytes from of mice from was are have FABP in adipocytes and the of the FABP mice of the FABP5 gene from the in of in the of the of was in the of the of to the of the of the from the to that the binding to the of adipocyte are to lipid the total of in the to the to the of the gene the of the of FABP5 in of 150% in total adipocyte in to the mice, adipocytes of the total adipocyte to the type of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: from the and the FABP5 transgenic to from the type the of the In the FABP5 transgenic mice increased adipocyte lipolysis in both the basal and the in fatty acid was in that in in and 150% in total that adipocytes from the mice have reduced lipolysis the to of report J. in adipocyte fatty acid binding protein mice the fatty acid binding in the in lipolysis was have to in the were in the were of the in lipolysis of total FABP level that the total FABP and FABP the of FABP and the were in the FABP5 transgenic mice and to of the the in lipolysis the total level of to in in of the of adipocyte protein of adipocyte and reduced lipolysis in the studies are the of that to and of to lipolysis are in both have in the adipocyte to of fatty acid was of Previous studies have that on of from and of from in the adipocyte fatty acid binding of the FABP5 transgenic mice increased levels FABP5 transgenic mice both and in in the total FABP level to the mice are FABP5 transgenic mice are to that lipolysis to that levels are the of mice, on reduced in and lipid in mice the FABP and the we have FABP5 transgenic levels of in adipocytes 150% the total FABP to the type and have increased basal and of in adipocytes the of the in in the of that and to in and have in fatty acid from fatty acid binding proteins are from in lipid and of intracellular fatty proteins and fatty and Lipid Res. of the have of the that the the J. fatty acid the the FABP of proteins in and binding of fatty and in have have to intracellular of fatty and and of intracellular fatty fatty and Lipid Res. fatty protein and Fatty acid in the in lipid and the of of and fatty in of and lipid of and adipocytes in to and in the of the proteins in thereby and of the adipocyte J. and of the of and from adipocyte to J. from the FABP are in the adipocyte fatty acid binding protein FABP5 epithelial fatty acid binding protein In the to that of in the adipocyte of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: the protein proteins fatty and of protein intracellular in of gene in fatty and of the intracellular lipid binding proteins of In to in adipocytes, in and of epithelial and fatty protein and Fatty acid binding protein in of the Res. protein in J. of and of in of the and fatty acid binding proteins acid in the of Res. Res. of of have the of to in FABP fatty protein and reduced in J. the fatty acid binding protein in fatty acid J. fatty acid from mice the fatty acid binding protein Res. mice reduced basal isoproterenol-stimulated lipolysis in and in the protein in fatty acid from the adipocyte of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: reduced in to and of the of adipocyte protein of adipocyte the of the FABP5 gene in adipocytes, in reduced total FABP level in FABP to of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: of from in the adipocyte fatty acid binding the reduced lipolysis in mice to the of the the of the in the total FABP the levels of of the the type of FABP to transgenic was that the FABP5 gene in the adipocyte the Herein, we report that increased total FABP level of to increased level of and in the level of in of from FABP5 transgenic mice increased basal and isoproterenol-stimulated that lipolysis to total FABP and to FABP acid and were from Fatty acid were from were from was from fatty acid was from mice, and FABP5 transgenic mice were mice were of and were on to in the mice were and were to of the were to were and the of and transgenic FABP5 gene and of the protein from the the was of the of of gene the and was to of the the FABP5 FABP5 gene was the the of in of of gene the were and of the to the and was and were in the of were of total and FABP5 to from FABP5 transgenic the FABP5 transgenic were and of to that and was levels of were in and to of protein were of and in proteins were to and and in were and and was the was on and FABP was from the protein the of the of from to mice were and in and and to were adipocytes were and in and in of the was and was to and fatty were of in were to was and the was were and to the lipid was of lipid in and Lipid Res. the were the and to the and acid to the that of the were in the total were from the in the were and was and the were and lipid were acid were in Fatty acid were and was fatty acid were of to of fatty acid was to the total the of adipocyte were in of in and was the of was the of to the adipocytes from the total fatty was the from of mice in of adipocyte fatty acid were in and acid were was of acid to the in acid of were and in were the of on to the fatty from the were and and the of acid in the was are was the are acid and were from Fatty acid were from were from was from fatty acid was from acid and were from Fatty acid were from were from was from fatty acid was from mice, and FABP5 transgenic mice were mice were of and were on to in the mice were and were to of the were to were and the of and mice, and FABP5 transgenic mice were mice were of and were on to in the mice were and were to of the were to were and the of and FABP5 transgenic FABP5 gene and of the protein from the the was of the of of gene the and was to of the the FABP5 FABP5 gene was the the of in of of gene the were and of the to the and was and were in the of were of total and FABP5 to from FABP5 transgenic the FABP5 transgenic were and of to that and was FABP5 gene and of the protein from the the was of the of of gene the and was to of the the FABP5 FABP5 gene was the the of in of of gene the were and of the to the and was and were in the of were of total and FABP5 to from FABP5 transgenic the FABP5 transgenic were and of to that and was levels of were in and to of protein were of and in proteins were to and and in were and and was the was on and FABP was from the protein the of the were in and to of protein were of and in proteins were to and and in were and and was the was on and FABP was from the protein the of the of from to mice were and in and and to were adipocytes were and in and in of the was and was to from to mice were and in and and to were adipocytes were and in and in of the was and was to Lipid and fatty were of in were to was and the was were and to the lipid was of lipid in and Lipid Res. the were the and to the and acid to the that of the were in the total were from the in the were and was and the were and lipid were fatty were of in were to was and the was were and to the lipid was of lipid in and Lipid Res. the were the and to the and acid to the that of the were in the total were from the in the were and was and the were and lipid were Fatty acid were in Fatty acid were and was fatty acid were of to of fatty acid was to the total the were in Fatty acid were and was fatty acid were of to of fatty acid was to the total the of adipocyte were in of in and was the of was the of to the adipocytes from the total fatty was the from of mice in were in of in and was the of was the of to the adipocytes from the total fatty was the from of mice in of adipocyte fatty acid were in and acid were was of acid to the in acid of were and in were the of on to the fatty from the were and and the of acid in the was were in and acid were was of acid to the in acid of were and in were the of on to the fatty from the were and and the of acid in the was are was the are are was the are the that fatty acid transgenic was that levels of FABP5 in the FABP5 gene the adipocyte of the FABP5 gene and of the was the on the were to mice, and were the to type of the in the were and of to of was from the FABP5 gene to the that of the FABP5 transgenic mice in in of the adipocytes from the FABP5 transgenic mice were the were on from and of and FABP5 transgenic FABP adipocyte fatty acid binding epithelial fatty acid binding was and to the of Fatty acid binding protein levels were and the were to of was were on from of to FABP5 transgenic mice to in were on adipocyte protein to the was FABP5 in adipocytes levels of and were to of protein protein and both in In adipocytes, levels are protein levels are to total FABP level of protein and of In the adipocytes from FABP5 transgenic levels were to protein levels were to to 150% in FABP and of in to the mice, adipocyte FABP levels of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: the fatty acid binding and of and are are proteins and and of protein intracellular in and of the intracellular lipid binding proteins of the of in the FABP5 transgenic mice the of intracellular of and was on from the of and FABP5 transgenic the fatty were and from to fatty were and to and that to of the total fatty in the of intracellular fatty were the that in from to the of the total intracellular fatty acid in and FABP5 transgenic were to and was of mice are was were in the of the was in FABP5 transgenic to were and the fatty and of were the were in the of the levels in of in and FABP5 transgenic was and were fatty acid was on mice from are in adipocyte to Previous on adipocytes from the mice in basal and isoproterenol-stimulated the total FABP the and the of adipocytes from and FABP5 transgenic mice were in the of and the in the were in basal of was in the FABP5 transgenic mice to the in lipolysis was in to the of both to to the basal in in lipolysis in the FABP5 transgenic to the adipocytes both basal and lipolysis are in the FABP5 transgenic the levels of lipolysis are in the FABP5 transgenic adipocytes, that the of in the in lipolysis to the total levels of FABP the of the of fatty lipolysis of revealed fatty the of were fatty and were the the of fatty the of fatty isoproterenol-stimulated lipolysis was to the of the of intracellular the of fatty isoproterenol-stimulated lipolysis in mice in of from isoproterenol-stimulated adipocytes from and FABP5 transgenic were to and of the total was of mice are was were in the of in adipocyte lipid the to fatty was adipocytes were and acid that was in the to fatty in the FABP5 transgenic adipocytes to the type the adipocytes the acid in the to the in the of acid levels of in the FABP5 studies are to to FABP levels in adipocytes in in the level of fatty acid in acid in adipocytes from and FABP5 transgenic was acid and FABP5 were in adipocytes from of mice from was are the that fatty acid transgenic was that levels of FABP5 in the FABP5 gene the adipocyte of the FABP5 gene and of the was the on the were to mice, and were the to type of the in the were and of to of was from the FABP5 gene to the that of the FABP5 transgenic mice in in of the adipocytes from the FABP5 transgenic mice were the were on from adipocyte fatty acid binding epithelial fatty acid binding was and to the of Fatty acid binding protein levels were and the were to of was were on from of to FABP5 transgenic mice to were on adipocyte protein to the was FABP5 in adipocytes levels of and were to of protein protein and both in In adipocytes, levels are protein levels are to total FABP level of protein and of In the adipocytes from FABP5 transgenic levels were to protein levels were to to 150% in FABP and of in to the mice, adipocyte FABP levels of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: the fatty acid binding and of and are are proteins and and of protein intracellular in and of the intracellular lipid binding proteins of the of in the FABP5 transgenic mice the of intracellular of and was on from the of and FABP5 transgenic the fatty were and from to fatty were and to and that to of the total fatty in the of intracellular fatty were the that in from to the of the total intracellular were to and was of mice are was were the of the was in FABP5 transgenic to were and the fatty and of were the were in the of the of in and FABP5 transgenic was and were fatty acid was on mice from are adipocyte to Previous on adipocytes from the mice in basal and isoproterenol-stimulated the total FABP the and the of adipocytes from and FABP5 transgenic mice were in the of and the in the were in basal of was in the FABP5 transgenic mice to the in lipolysis was in to the of both to to the basal in in lipolysis in the FABP5 transgenic to the adipocytes both basal and lipolysis are in the FABP5 transgenic the levels of lipolysis are in the FABP5 transgenic adipocytes, that the of in the in lipolysis to the total levels of FABP the of the of fatty lipolysis of revealed fatty the of were fatty and were the the of fatty the of fatty isoproterenol-stimulated lipolysis was to the of the of intracellular the of from isoproterenol-stimulated adipocytes from and FABP5 transgenic were to and of the total was of mice are was were the of in adipocyte lipid the to fatty was adipocytes were and acid that was in the to fatty in the FABP5 transgenic adipocytes to the type the adipocytes the acid in the to the in the of acid levels of in the FABP5 studies are to to FABP levels in adipocytes in in the level of fatty acid in have FABP in adipocytes and the of the FABP mice of the FABP5 gene from the in of in the of the of was in the of the of to the of the of the from the to that the binding to the of adipocyte are to lipid the total of in the to the to the of the gene the of the of FABP5 in of 150% in total adipocyte in to the mice, adipocytes of the total adipocyte to the type of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: from the and the FABP5 transgenic to from the type the of the In the FABP5 transgenic mice increased adipocyte lipolysis in both the basal and the in fatty acid was in that in in and 150% in total that adipocytes from the mice have reduced lipolysis the to of report J. in adipocyte fatty acid binding protein mice the fatty acid binding in the in lipolysis was have to in the were in the were of the in lipolysis of total FABP level that the total FABP and FABP the of FABP and the were in the FABP5 transgenic mice and to of the the in lipolysis the total level of to in in of the of adipocyte protein of adipocyte and reduced lipolysis in the studies are the of that to and of to lipolysis are in both have in the adipocyte to of fatty acid was of Previous studies have that on of from and of from in the adipocyte fatty acid binding of the FABP5 transgenic mice increased levels FABP5 transgenic mice both and in in the total FABP level to the mice are FABP5 transgenic mice are to that lipolysis to that levels are the of mice, on reduced in and lipid in mice the FABP and the we have FABP5 transgenic levels of in adipocytes 150% the total FABP to the type and have increased basal and of in adipocytes the of the in in the of that and to in and have in fatty acid from have FABP in adipocytes and the of the FABP mice of the FABP5 gene from the in of in the of the of was in the of the of to the of the of the from the to that the binding to the of adipocyte are to lipid the total of in the to the to the of the gene the of the of FABP5 in of 150% in total adipocyte in to the mice, adipocytes of the total adipocyte to the type of the adipocyte protein gene lipolysis and fatty acid Lipid Res. 40: from the and the FABP5 transgenic to from the type the of the In the FABP5 transgenic mice increased adipocyte lipolysis in both the basal and the in fatty acid was in that in in and 150% in total that adipocytes from the mice have reduced lipolysis the to of report J. in adipocyte fatty acid binding protein mice the fatty acid binding in the in lipolysis was have to in the were in the were of the in lipolysis of total FABP level that the total FABP and FABP the of FABP and the were in the FABP5 transgenic mice and to of the the in lipolysis the total level of to in in of the of adipocyte protein of adipocyte and reduced lipolysis in the studies are the of that to and of to lipolysis are in both have in the adipocyte to of fatty acid was of Previous studies have that on of from and of from in the adipocyte fatty acid binding of the FABP5 transgenic mice increased levels FABP5 transgenic mice both and in in the total FABP level to the mice are FABP5 transgenic mice are to that lipolysis to that levels are the of mice, on reduced in and lipid in mice the FABP and the In we have FABP5 transgenic levels of in adipocytes 150% the total FABP to the type and have increased basal and of in adipocytes the of the in in the of that and to in and have in fatty acid from of the and the of and of the was of and and and adipocyte fatty acid binding protein epithelial fatty acid binding protein fatty acid binding protein