title: Transorgan fluxes in a porcine model reveal a central role for liver in acylcarnitine metabolism.
abstract: Acylcarnitines are derived from mitochondrial acyl-CoA metabolism and have been associated with diet-induced insulin resistance. However, plasma acylcarnitine profiles have been shown to poorly reflect whole body acylcarnitine metabolism. We aimed to clarify the individual role of different organ compartments in whole body acylcarnitine metabolism in a fasted and postprandial state in a porcine transorgan arteriovenous model. Twelve cross-bred pigs underwent surgery where intravascular catheters were positioned before and after the liver, gut, hindquarter muscle compartment, and kidney. Before and after a mixed meal, we measured acylcarnitine profiles at several time points and calculated net transorgan acylcarnitine fluxes. Fasting plasma acylcarnitine concentrations correlated with net hepatic transorgan fluxes of free and C2- and C16-carnitine. Transorgan acylcarnitine fluxes were small, except for a pronounced net hepatic C2-carnitine production. The peak of the postprandial acylcarnitine fluxes was between 60 and 90 min. Acylcarnitine production or release was seen in the gut and liver and consisted mostly of C2-carnitine. Acylcarnitines were extracted by the kidney. No significant net muscle acylcarnitine flux was observed. We conclude that liver has a key role in acylcarnitine metabolism, with high net fluxes of C2-carnitine both in the fasted and fed state, whereas the contribution of skeletal muscle is minor. These results further clarify the role of different organ compartments in the metabolism of different acylcarnitine species.
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Marieke G
authors.initials: MG
authors.lastname: Schooneman
authors.affiliation: Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A & M University, College Station, Texas; and.
authors.forename: Gabriella A M
authors.initials: GA
authors.lastname: Ten Have
authors.affiliation: Department of Clinical Chemistry, Laboratory Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
authors.forename: Naomi
authors.initials: N
authors.lastname: van Vlies
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Sander M
authors.initials: SM
authors.lastname: Houten
authors.affiliation: Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A & M University, College Station, Texas; and.
authors.forename: Nicolaas E P
authors.initials: NE
authors.lastname: Deutz
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; m.r.soeters@amc.uva.nl.
authors.forename: Maarten R
authors.initials: MR
authors.lastname: Soeters
mesh_terms: D000108:Acetylcarnitine / Q000097:blood / Q000378:metabolism; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism; D002408:Catheters, Indwelling; D003433:Crosses, Genetic; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007668:Kidney / Q000098:blood supply / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000098:blood supply / Q000378:metabolism*; D008954:Models, Biological; D000069463:Olive Oil; D009928:Organ Specificity; D010172:Palmitoylcarnitine / Q000097:blood / Q000378:metabolism; D010938:Plant Oils / Q000008:administration & dosage / Q000378:metabolism; D019518:Postprandial Period; D034421:Sus scrofa
chemical_list: D000069463:Olive Oil; D010938:Plant Oils; C116917:acylcarnitine; D010172:Palmitoylcarnitine; D000108:Acetylcarnitine; D002331:Carnitine
keywords: acylcarnitines; fatty acid oxidation; mixed-meal test; pigs