title: Acyl-coenzyme A binding protein expression alters liver fatty acyl-coenzyme A metabolism.
abstract: Although studies in vitro and in yeast suggest that acyl-CoA binding protein ACBP may modulate long-chain fatty acyl-CoA (LCFA-CoA) distribution, its physiological function in mammals is unresolved. To address this issue, the effect of ACBP on liver LCFA-CoA pool size, acyl chain composition, distribution, and transacylation into more complex lipids was examined in transgenic mice expressing a higher level of ACBP. While ACBP transgenic mice did not exhibit altered body or liver weight, liver LCFA-CoA pool size increased by 69%, preferentially in saturated and polyunsaturated, but not monounsaturated, LCFA-CoAs. Intracellular LCFA-CoA distribution was also altered such that the ratio of LCFA-CoA content in (membranes, organelles)/cytosol increased 2.7-fold, especially in microsomes but not mitochondria. The increased distribution of specific LCFA-CoAs to the membrane/organelle and microsomal fractions followed the same order as the relative LCFA-CoA binding affinity exhibited by murine recombinant ACBP: saturated > monounsaturated > polyunsaturated C14-C22 LCFA-CoAs. Consistent with the altered microsomal LCFA-CoA level and distribution, enzymatic activity of liver microsomal glycerol-3-phosphate acyltransferase (GPAT) increased 4-fold, liver mass of phospholipid and triacylglyceride increased nearly 2-fold, and relative content of monounsaturated C18:1 fatty acid increased 44% in liver phospholipids. These effects were not due to the ACBP transgene altering the protein levels of liver microsomal acyltransferase enzymes such as GPAT, lysophosphatidic acid acyltransferase (LAT), or acyl-CoA cholesterol acyltransferase 2 (ACAT-2). Thus, these data show for the first time in a physiological context that ACBP expression may play a role in LCFA-CoA metabolism.
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, Texas 77843-4466, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Huang
authors.forename: Barbara P
authors.initials: BP
authors.lastname: Atshaves
authors.forename: Andrey
authors.initials: A
authors.lastname: Frolov
authors.forename: Ann B
authors.initials: AB
authors.lastname: Kier
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Schroeder
mesh_terms: D000214:Acyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D026261:Diazepam Binding Inhibitor / Q000737:chemistry* / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000096:biosynthesis / Q000378:metabolism; D006017:Glycolipids / Q000096:biosynthesis; D050356:Lipid Metabolism; D008055:Lipids / Q000145:classification; D008099:Liver / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009929:Organ Size / Q000235:genetics; D010743:Phospholipids / Q000096:biosynthesis / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000096:biosynthesis; D014280:Triglycerides / Q000096:biosynthesis / Q000378:metabolism; D000097587:Sterol O-Acyltransferase 2
chemical_list: D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005992:Glycerol-3-Phosphate O-Acyltransferase; D006017:Glycolipids; D008055:Lipids; D010743:Phospholipids; D011994:Recombinant Proteins; D002785:Sterol O-Acyltransferase; D014280:Triglycerides; D000097587:Sterol O-Acyltransferase 2; C015903:glycerolglycolipids