title: Impaired oxidative capacity due to decreased CPT1b levels as a contributing factor to fat accumulation in obesity.
abstract: To characterize mechanisms responsible for fat accumulation we used a selectively bred obesity-prone (OP) and obesity-resistant (OR) rat model where the rats were fed a Western diet for 76 days. Body composition was assessed by magnetic resonance imaging scans, and as expected, the OP rats developed a higher degree of fat accumulation compared with OR rats. Indirect calorimetry showed that the OP rats had higher respiratory exchange ratio (RER) compared with OR rats, indicating an impaired ability to oxidize fat. The OP rats had lower expression of carnitine palmitoyltransferase 1b in intra-abdominal fat, and higher expression of stearoyl-CoA desaturase 1 in subcutaneous fat compared with OR rats, which could explain the higher fat accumulation and RER values. Basal metabolic parameters were also examined in juvenile OP and OR rats before and during the introduction of the Western diet. Juvenile OP rats likewise had higher RER values, indicating that this trait may be a primary and contributing factor to their obese phenotype. When the adult obese rats were exposed to the orexigenic and adipogenic hormone ghrelin, we observed increased RER values in both OP and OR rats, while OR rats were more sensitive to the orexigenic effects of ghrelin as well as ghrelin-induced attenuation of activity and energy expenditure. Thus increased fat accumulation characterizing obesity may be caused by impaired oxidative capacity due to decreased carnitine palmitoyltransferase 1b levels in the white adipose tissue, whereas ghrelin sensitivity did not seem to be a contributing factor.
authors: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Section for Metabolic Receptology and Enteroendocrinology, The Novo Nordisk Foundation Center for basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;
authors: Cecilia
authors: C
authors: Ratner
authors: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Section for Metabolic Receptology and Enteroendocrinology, The Novo Nordisk Foundation Center for basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;
authors: Andreas Nygaard
authors: AN
authors: Madsen
authors: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Section for Metabolic Receptology and Enteroendocrinology, The Novo Nordisk Foundation Center for basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;
authors: Line Vildbrad
authors: LV
authors: Kristensen
authors: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Section for Metabolic Receptology and Enteroendocrinology, The Novo Nordisk Foundation Center for basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark;
authors: Louise Julie
authors: LJ
authors: Skov
authors: Department of Biomedical Sciences, Cellular and Metabolic Research Section, Symbion, Copenhagen, Denmark;
authors: Katrine Seide
authors: KS
authors: Pedersen
authors: Department of Biomedical Sciences, Cellular and Metabolic Research Section, Symbion, Copenhagen, Denmark;
authors: Ole Hartvig
authors: OH
authors: Mortensen
authors: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and.
authors: Gitte Moos
authors: GM
authors: Knudsen
authors: Novo Nordisk Diabetes Research Unit, Novo Nordisk A/S, Maaloev, Denmark.
authors: Kirsten
authors: K
authors: Raun
authors: Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Section for Metabolic Receptology and Enteroendocrinology, The Novo Nordisk Foundation Center for basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; holst@sund.ku.dk.
authors: Birgitte
authors: B
authors: Holst
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D002153:Calorimetry, Indirect; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D015536:Down-Regulation; D004435:Eating; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation; D054439:Ghrelin / Q000008:administration & dosage; D007031:Hypothalamus / Q000201:enzymology; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D020738:Leptin / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology; D009765:Obesity / Q000097:blood / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D010084:Oxidation-Reduction; D051381:Rats; D050151:Subcutaneous Fat / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D013997:Time Factors; D015430:Weight Gain
chemical_list: D054439:Ghrelin; D007328:Insulin; D020738:Leptin; C000600281:CPT1b protein, rat; D002334:Carnitine O-Palmitoyltransferase
keywords: adipose tissue; ghrelin; indirect calorimetry; polygenic obese; respiratory exchange ratio