Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity
Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of car...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-05-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S002222752033981X |
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| author | Ilse Duivenvoorden Bas Teusink Patrick C.N. Rensen Folkert Kuipers Johannes A. Romijn Louis M. Havekes Peter J. Voshol |
| author_facet | Ilse Duivenvoorden Bas Teusink Patrick C.N. Rensen Folkert Kuipers Johannes A. Romijn Louis M. Havekes Peter J. Voshol |
| author_sort | Ilse Duivenvoorden |
| collection | DOAJ |
| description | Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely inhibit hepatic FA oxidation and investigated whether the FAs were rerouted into VLDL secretion and whether this would affect hepatic glucose production. After an overnight fast, male APOE3*Leiden transgenic mice received an oral dose of 10 mg/kg MP. Administration of MP led to an 83% reduction in plasma β-hydroxybutyrate (ketone body) levels compared with vehicle-treated mice (0.47 ± 0.07 vs. 2.81 ± 0.16 mmol/l, respectively; P < 0.01), indicative of impaired ketogenesis. Plasma FFA levels were increased by 32% and cholesterol and insulin levels were decreased by 17% and 50%, respectively, in MP-treated mice compared with controls. MP treatment led to a 30% increase in liver triglyceride (TG) content. Surprisingly, no effect on hepatic VLDL-TG production was observed between the groups at 8 h after MP administration. In addition, the capacity of insulin to suppress endogenous glucose production was unaffected in MP-treated mice compared with controls.In conclusion, acute inhibition of FA oxidation increases hepatic lipid content but does not stimulate hepatic VLDL secretion or reduce insulin sensitivity. |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T08:37:54Z |
| publishDate | 2005-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-7c72975e002643ed97419242b1a727ce2022-12-21T21:56:26ZengElsevierJournal of Lipid Research0022-22752005-05-01465988993Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivityIlse Duivenvoorden0Bas Teusink1Patrick C.N. Rensen2Folkert Kuipers3Johannes A. Romijn4Louis M. Havekes5Peter J. Voshol6Netherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsNetherlands Organization for Applied Scientific Research-Quality of Life, Gaubius Laboratory, Leiden, The Netherlands; Department of General Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Center for Liver, Digestive, and Metabolic Diseases, Laboratory of Pediatrics, University Hospital Groningen, Groningen, The NetherlandsHepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely inhibit hepatic FA oxidation and investigated whether the FAs were rerouted into VLDL secretion and whether this would affect hepatic glucose production. After an overnight fast, male APOE3*Leiden transgenic mice received an oral dose of 10 mg/kg MP. Administration of MP led to an 83% reduction in plasma β-hydroxybutyrate (ketone body) levels compared with vehicle-treated mice (0.47 ± 0.07 vs. 2.81 ± 0.16 mmol/l, respectively; P < 0.01), indicative of impaired ketogenesis. Plasma FFA levels were increased by 32% and cholesterol and insulin levels were decreased by 17% and 50%, respectively, in MP-treated mice compared with controls. MP treatment led to a 30% increase in liver triglyceride (TG) content. Surprisingly, no effect on hepatic VLDL-TG production was observed between the groups at 8 h after MP administration. In addition, the capacity of insulin to suppress endogenous glucose production was unaffected in MP-treated mice compared with controls.In conclusion, acute inhibition of FA oxidation increases hepatic lipid content but does not stimulate hepatic VLDL secretion or reduce insulin sensitivity.http://www.sciencedirect.com/science/article/pii/S002222752033981Xtriglyceridesfatty acidssteatosisglucose metabolismvery low density lipoprotein |
| spellingShingle | Ilse Duivenvoorden Bas Teusink Patrick C.N. Rensen Folkert Kuipers Johannes A. Romijn Louis M. Havekes Peter J. Voshol Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity Journal of Lipid Research triglycerides fatty acids steatosis glucose metabolism very low density lipoprotein |
| title | Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity |
| title_full | Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity |
| title_fullStr | Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity |
| title_full_unstemmed | Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity |
| title_short | Acute inhibition of hepatic β-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity |
| title_sort | acute inhibition of hepatic β oxidation in apoe 3leiden mice does not affect hepatic vldl secretion or insulin sensitivity |
| topic | triglycerides fatty acids steatosis glucose metabolism very low density lipoprotein |
| url | http://www.sciencedirect.com/science/article/pii/S002222752033981X |
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