Key points are not available for this paper at this time.
Long chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide substrates for both anabolic and catabolic pathways. We have hypothesized that each of the five ACSL isoforms partitions FA toward specific downstream pathways. Acsl1 mRNA is increased in cells under both lipogenic and oxidative conditions. To elucidate the role of ACSL1 in hepatic lipid metabolism, we overexpressed an Acsl1 adenovirus construct (Ad-Acsl1) in rat primary hepatocytes. Ad-ACSL1, located on the endoplasmic reticulum but not on mitochondria or plasma membrane, increased ACS specific activity 3.7-fold. With 100 or 750 μm 1-14Coleate, Ad-Acsl1 increased and and and and Ad-Acsl1 not or of FA the of Ad-Acsl1 on lipid and but in Ad-Acsl1 that ACSL1 increased of and for and in and the that ACSL1 increased Ad-Acsl1 cells increased but not FA the that Ad-Acsl1 increased FA and FA toward and and Long chain acyl-CoA synthetases (ACSL) activate fatty acids (FA) and provide substrates for both anabolic and catabolic pathways. We have hypothesized that each of the five ACSL isoforms partitions FA toward specific downstream pathways. Acsl1 mRNA is increased in cells under both lipogenic and oxidative conditions. To elucidate the role of ACSL1 in hepatic lipid metabolism, we overexpressed an Acsl1 adenovirus construct (Ad-Acsl1) in rat primary hepatocytes. Ad-ACSL1, located on the endoplasmic reticulum but not on mitochondria or plasma membrane, increased ACS specific activity 3.7-fold. With 100 or 750 μm 1-14Coleate, Ad-Acsl1 increased and and and and Ad-Acsl1 not or of FA the of Ad-Acsl1 on lipid and but in Ad-Acsl1 that ACSL1 increased of and for and in and the that ACSL1 increased Ad-Acsl1 cells increased but not FA the that Ad-Acsl1 increased FA and FA toward and and acyl-CoA synthetases chain acyl-CoA acyl-CoA endoplasmic fatty and of of chain acyl-CoA acyl-CoA endoplasmic fatty and of of the in FA FA acyl-CoA both anabolic and catabolic and the of is hepatic and ACSL each the of have and in ACSL isoforms have and and and the of is We hypothesized of ACSL isoforms FA for the of ACSL in FA an of and but not or in in and but and that ACSL ACSL1 and in in the of in or and is overexpressed in rat partitions FA toward and but not toward or the of ACSL isoforms in in we that that ACSL1 is for in and the of ACSL1 in role for ACSL1 in is in the and of and the of FA Acsl1 mRNA is or that and hepatic ACS specific activity and Acsl1 mRNA in and that have fatty the in of role for ACSL1 in FA for that for both FA and FA ACS activity in rat and Acsl1 mRNA in rat and in the rat is in the of the Acsl1 elucidate the specific role of ACSL1 in hepatic FA metabolism, we overexpressed rat ACSL1 in rat primary hepatocytes. We hypothesized that ACSL1 FA toward specific lipid and and for adenovirus and cells the and and and and of rat Acsl1 the and of the is the in the construct and the of and activity of the construct cells for ACS activity and construct an cells for adenovirus (Ad-Acsl1) and the under of the for and the and in and the and of cells or cells in and cells or for in and and Ad-Acsl1 of or for cells or cells cells and the or of or of for cells and of for and and or cells in of of FA in for ACS activity that in both and Acsl1 cells not for of 100 μm or 750 μm cells μm or for or in and adenovirus for and 750 μm in the of μm or μm in the of 750 μm the cells or in and for an in or and cells and of the lipid the cells and on in for or in for lipid in or and for ACS and ACSL Ad-Acsl1 or and in and and on the ACS specific activity the of in the of and μm in in of for of of and the and on and the and and or Ad-Acsl1 an of for and on an and in for the and for for rat primary in on and Ad-Acsl1 for cells in for and in for cells and in in for and and for for or for in for and in or and or for for in the on the and and and for cells for or Ad-Acsl1 or 750 μm for lipid an each and of Acsl1 ACS in rat primary or an adenovirus rat Acsl1 the (Ad-Acsl1) and the ACS specific activity and an ACS specific activity not in Ad-Acsl1 increased ACS specific activity Ad-Acsl1 increased ACS specific activity for primary of that the in ACS specific activity the of the in the of the increased the of and the adenovirus we and ACS specific activity increased 3.7-fold. in rat Acsl1 increased mRNA but mRNA not not ACSL1 but or that ACSL1 in rat is in and but not in We the of overexpressed of the and but not the of the of ACSL1 on the plasma We an in is an in primary hepatocytes. Ad-Acsl1 for and primary the of or cells and in each and of on cells and the of and that the for and mitochondria of and an an on the that is of not of on in and on the of both not on we cells for and but not for the of in not for ACSL1 the of overexpressed ACSL1 in primary the ACSL1 in but and the of overexpressed ACSL1 on lipid metabolism, we the 100 or 750 μm 1-14Coleate, of FA under or 100 μm of Ad-Acsl1 750 μm in of in cells and the of the in the of both of 750 μm increased in both and the of ACSL1 not the adenovirus not the not the that Ad-Acsl1 the mRNA of the that in in cells not increased but not or Ad-Acsl1 cells 100 μm or 750 μm for and and lipid under and or cells or 750 μm for and in that Ad-Acsl1 substrates for the of in Ad-Acsl1 cells both 100 and 750 μm To the of in cells that we cells and 750 μm of ACSL1 not of that ACSL1 on Ad-Acsl1 increased and 100 and 750 μm 100 μm Ad-Acsl1 increased and 750 μm Ad-Acsl1 increased and in that of ACSL1 and that and increased or Acsl1 for and 100 μm or 750 μm for and and in that Ad-Acsl1 the of for overexpressed ACSL1 for FA we in the an of FA is of is of in cells and cells both 100 and 750 μm and in the mRNA of the for not of ACSL1 not FA but not and or Ad-Acsl1 under 100 μm or 750 μm for and the cells and and FA and and and in and Ad-Acsl1 the of in Ad-Acsl1 and Ad-Acsl1 the of the of and not that of ACSL1 the of of ACSL1 the of FA is overexpressed in rat cells or ACSL1 is overexpressed in the of FA is that FA the of To ACSL1 FA we the of and and Ad-Acsl1 not the of FA 100 μm or 750 μm in FA not ACSL1 ACSL1 or in and the and we the of of increased or To we cells 750 μm for and the of for of the the of ACSL1 the of in an and in the of in the in the of and of in the of that Ad-Acsl1 FA of and the of in the in the cells that overexpressed ACSL1 that ACSL1 in and FA that of ACSL1 in hepatocytes. and or Ad-Acsl1 for 750 μm for and for lipid or and FA for under in lipid or in and in of the the in cells and Ad-Acsl1 and the in cells and Ad-Acsl1 the and the in and that Ad-Acsl1 the of and both the and Ad-Acsl1 cells the the of in increased the in Ad-Acsl1 in the the and the that ACSL1 the of of the cells the that the in and the of FA ACSL1 and and overexpressed ACSL1 we μm in the of 750 μm for or for in the of the of overexpressed ACSL1 increased and and that ACSL1 increased of and ACSL1 increased and is that the in and the that ACSL1 not the in the the of ACSL1 on and and in the cells that ACSL1 lipid in the and and increased and and FA or Ad-Acsl1 for μm in the of 750 μm and or for lipid and or and FA for under in lipid in cells and Ad-Acsl1 the of FA and both FA the and FA that FA have We that FA but not FA To the of we the ACSL1 increased and and the the overexpressed ACSL1 and not of on the that of the in FA that ACSL1 activate FA both and and the of and of that of ACSL1 FA specific in rat primary and that of ACSL1 in of in and cells that overexpressed ACSL1 that and in of ACSL1 in the of Acsl1 mRNA isoforms in ACS specific activity and Acsl1 mRNA is in and in that the of ACSL1 in of ACSL1 and overexpressed ACSL1 in not or in in the cells the that ACSL1 the of lipid or increased of We the the an in the the increased in cells the the of the the increased in and and in the that ACSL1 FA both and of and and ACSL1 in both and rat in of overexpressed ACSL1 but not mitochondria or plasma of and not in the in is in in of toward is the that and increased and in Acsl1 and in Ad-Acsl1 cells the ACSL1 have increased FA FA or the of of overexpressed in rat cells in in or an in that ACSL1 and FA of in cells that overexpressed mRNA or of the 750 μm not that acyl-CoA both and Ad-Acsl1 cells the the Ad-Acsl1 cells we that overexpressed ACSL1 ACSL1 of in rat not ACSL1 not the of FA the but the for hepatic Acsl1 is of not that ACSL1 FA the of in FA activity of increased the of and in FA and an in the of of Acsl1 Ad-Acsl1 cells the for the role of in the and of is in primary rat and cells and of and in cells in rat is not the for and the of not in in the of FA and for the and of ACSL isoforms the of FA and FA the of of FA the have the of FA that not the of FA that is and We the FA in and and in of that ACSL1 not the of FA hepatocytes. ACSL1 on the plasma of is not in and we that ACSL1 is not on the plasma membrane, of FA and in the of or downstream that the of ACSL1 for we is for FA Ad-Acsl1 increased and of FA for that and in FA that of ACSL1 FA and but not in the the of FA have of the of and that overexpressed ACSL1 the in for ACSL1 not that the in that ACSL1 FA toward specific of rat Acsl1 in rat primary toward and and ACSL1 increased the of and but the of for role in and of ACSL1 in not of or the of FA that ACSL1 FA in on the of ACSL1 or the of specific each overexpressed ACSL1 both FA and FA but the acyl-CoA pathways. that ACSL1 in an role in FA of and and acyl-CoA synthetases chain acyl-CoA acyl-CoA endoplasmic fatty and of of chain acyl-CoA acyl-CoA endoplasmic fatty and of of the in FA FA acyl-CoA both anabolic and catabolic and the of is hepatic and ACSL each the of have and in ACSL isoforms have and and and the of is We hypothesized of ACSL isoforms FA pathways. for the of ACSL in FA an of and but not or in in and but and that ACSL ACSL1 and in in the of in or and is overexpressed in rat partitions FA toward and but not toward or the of ACSL isoforms in in we that that ACSL1 is for in and the of ACSL1 in role for ACSL1 in is in the and of and the of FA Acsl1 mRNA is or that and hepatic ACS specific activity and Acsl1 mRNA in and that have fatty the in of role for ACSL1 in FA for that for both FA and FA ACS activity in rat and Acsl1 mRNA in rat and in the rat is in the of the Acsl1 To elucidate the specific role of ACSL1 in hepatic FA metabolism, we overexpressed rat ACSL1 in rat primary hepatocytes. We hypothesized that ACSL1 FA toward specific lipid and and for adenovirus and cells the and and and and of rat Acsl1 the and of the is the in the construct and the of and activity of the construct cells for ACS activity and construct an cells for adenovirus (Ad-Acsl1) and the under of the for and the and in and the and of cells or cells in and cells or for in and and Ad-Acsl1 of or for cells or cells cells and the or of or of for cells and of for and and or cells in of of FA in for ACS activity that in both and Acsl1 cells not for of 100 μm or 750 μm cells μm or for or in and adenovirus for and 750 μm in the of μm or μm in the of 750 μm the cells or in and for an in or and cells and of the lipid the cells and on in for or in for lipid in or and for ACS and ACSL Ad-Acsl1 or and in and and on the ACS specific activity the of in the of and μm in in of for of of and the and on and the and and or Ad-Acsl1 an of for and on an and in for the and for for rat primary in on and Ad-Acsl1 for cells in for and in for cells and in in for and and for for or for in for and in or and or for for in the on the and and and for cells for or Ad-Acsl1 or 750 μm for lipid an each and and for adenovirus and cells the and and and and of rat Acsl1 the and of the is the in the construct and the of and activity of the construct cells for ACS activity and construct an cells for adenovirus (Ad-Acsl1) and the under of the for and the and in and the and of cells or cells in and cells or for in and and Ad-Acsl1 of or for cells or cells cells and the or of or of for cells and of for and and or cells in of of FA in for ACS activity that in both and Acsl1 cells not for of 100 μm or 750 μm cells μm or for or in and adenovirus for and 750 μm in the of μm or μm in the of 750 μm the cells or in and for an in or and cells and of the lipid the cells and on in for or in for lipid in or and for ACS and ACSL Ad-Acsl1 or and in and and on the ACS specific activity the of in the of and μm in in of for of of 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overexpressed ACSL1 on lipid metabolism, we the 100 or 750 μm 1-14Coleate, of FA under or 100 μm of Ad-Acsl1 750 μm in of in cells and the of the in the of both of 750 μm increased in both and the of ACSL1 not the adenovirus not the not the that Ad-Acsl1 the mRNA of the that in in cells not increased but not or Ad-Acsl1 cells 100 μm or 750 μm for and and lipid under and or cells or 750 μm for and in that Ad-Acsl1 substrates for the of in Ad-Acsl1 cells both 100 and 750 μm To the of in cells that we cells and 750 μm of ACSL1 not of that ACSL1 on Ad-Acsl1 increased and 100 and 750 μm 100 μm Ad-Acsl1 increased and 750 μm Ad-Acsl1 increased and in that of ACSL1 and that and increased or Acsl1 for and 100 μm or 750 μm for and and in that Ad-Acsl1 the of for overexpressed ACSL1 for FA we in the an of FA is of is of in cells and cells both 100 and 750 μm and in the mRNA of the for not of ACSL1 not FA but not and or Ad-Acsl1 under 100 μm or 750 μm for and the cells and and FA and and and in 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lipid in the and and ACSL1 the of FA and both FA the and FA that FA have We that FA but not FA To the of we the ACSL1 increased and and the the overexpressed ACSL1 and not of on the that of the in FA that ACSL1 activate FA both and and the of and of that of ACSL1 FA specific in rat primary and that of ACSL1 in of in and cells that overexpressed ACSL1 that and in of ACSL1 in the of Acsl1 mRNA isoforms in ACS specific activity and Acsl1 mRNA is in and in that the of ACSL1 in of ACSL1 and overexpressed ACSL1 in not or in in the cells the that ACSL1 the of lipid or increased of We the the an in the the increased in cells the the of the the increased in and and in the that ACSL1 FA both and of and and ACSL1 in both and rat in of overexpressed ACSL1 but not mitochondria or plasma of and not in the in is in in of toward is the that and increased and in Acsl1 and in Ad-Acsl1 cells the ACSL1 have increased FA FA or the of of overexpressed in rat cells in in or an in that ACSL1 and FA of in cells that overexpressed mRNA or of the 750 μm not that acyl-CoA both and Ad-Acsl1 cells the the Ad-Acsl1 cells we that overexpressed ACSL1 ACSL1 of in rat not ACSL1 not the of FA the but the for hepatic Acsl1 is of not that ACSL1 FA the of in FA activity of increased the of and in FA and an in the of of Acsl1 Ad-Acsl1 cells the for the role of in the and of is in primary rat and cells and of and in cells in rat is not the for and the of not in in the of FA and for the and of ACSL isoforms the of FA and FA the of of FA the have the of FA that not the of FA that is and We the FA in and and in of that ACSL1 not the of FA hepatocytes. ACSL1 on the plasma of is not in and we that ACSL1 is not on the plasma membrane, of FA and in the of or downstream that the of ACSL1 for we is for FA Ad-Acsl1 increased and of FA for that and in FA that of ACSL1 FA and but not in the the of FA have of the of and that overexpressed ACSL1 the in for ACSL1 not that the in that ACSL1 FA toward specific of rat Acsl1 in rat primary toward and and ACSL1 increased the of and but the of for role in and of ACSL1 in not of or the of FA that ACSL1 FA in on the of ACSL1 or the of specific each overexpressed ACSL1 both FA and FA but the acyl-CoA pathways. that ACSL1 in an role in FA of and and of that of ACSL1 FA specific in rat primary and that of ACSL1 in of in and cells that overexpressed ACSL1 that and in of ACSL1 in the of Acsl1 mRNA isoforms in ACS specific activity and Acsl1 mRNA is in and in that the of ACSL1 in of ACSL1 and overexpressed ACSL1 in not or in in the cells the that ACSL1 the of lipid or increased of We the the an in the the increased in cells the the of the the increased in and and in the that ACSL1 FA both and of and and ACSL1 in both and rat in of overexpressed ACSL1 but not mitochondria or plasma of and not in the in is in in of toward is the that and increased and in Acsl1 and in Ad-Acsl1 cells the ACSL1 have increased FA FA or the of of overexpressed in rat cells in in or an in that ACSL1 and FA of in cells that overexpressed mRNA or of the 750 μm not that acyl-CoA both and Ad-Acsl1 cells the the Ad-Acsl1 cells we that overexpressed ACSL1 ACSL1 of in rat not ACSL1 not the of FA the but the for hepatic Acsl1 is of not that ACSL1 FA the of in FA activity of increased the of and in FA and an in the of of Acsl1 Ad-Acsl1 cells the for the role of in the and of is in primary rat and cells and of and in cells in rat is not the for and the of not in in the of FA and for the and of ACSL isoforms the of FA and FA the of of FA the have the of FA that not the of FA that is and We the FA in and and in of that ACSL1 not the of FA hepatocytes. ACSL1 on the plasma of is not in and we that ACSL1 is not on the plasma membrane, of FA and in the of or downstream that To the of ACSL1 for we is for FA Ad-Acsl1 increased and of FA for that and in FA that of ACSL1 FA and but not in the the of FA have of the of and that overexpressed ACSL1 the in for ACSL1 not that the in that ACSL1 FA toward specific of rat Acsl1 in rat primary toward and and ACSL1 increased the of and but the of for role in and of ACSL1 in not of or the of FA that ACSL1 FA in on the of ACSL1 or the of specific each overexpressed ACSL1 both FA and FA but the acyl-CoA pathways. that ACSL1 in an role in FA of and and We the and for the for and the for We of for
Li et al. (Sat,) studied this question.