title: Enhancing hepatic mitochondrial fatty acid oxidation stimulates eating in food-deprived mice.
abstract: Hepatic fatty acid oxidation (FAO) has long been implicated in the control of eating. Nevertheless, direct evidence for a causal relationship between changes in hepatic FAO and changes in food intake is still missing. Here we tested whether increasing hepatic FAO via adenovirus-mediated expression of a mutated form of the key regulatory enzyme of mitochondrial FAO carnitine palmitoyltransferase 1A (CPT1mt), which is active but insensitive to inhibition by malonyl-CoA, affects eating and metabolism in mice. CPT1mt expression increased hepatocellular CPT1 protein levels. This resulted in an increase in circulating ketone body levels in fasted CPT1mt-expressing mice, suggesting an increase in hepatic FAO. These mice did not show any significant changes in cumulative food intake, energy expenditure, or respiratory quotient after 4-h food deprivation. After 24-h food deprivation, however, the CPT1mt-expressing mice displayed increased food intake. Thus expression of CPT1mt in the liver increases hepatic FAO capacity, but does not inhibit eating. Rather, it may even stimulate eating after prolonged food deprivation. These data do not support the hypothesis that an increase in hepatic FAO decreases food intake.
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Abdelhak
authors.initials: A
authors.lastname: Mansouri
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Gustavo
authors.initials: G
authors.lastname: Pacheco-López
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Deepti
authors.initials: D
authors.lastname: Ramachandran
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Myrtha
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Claudia
authors.initials: C
authors.lastname: Leitner
authors.affiliation: INSERM, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Paris, France; and.
authors.forename: Carina
authors.initials: C
authors.lastname: Prip-Buus
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Switzerland;
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.affiliation: Department of Medical and Molecular Genetics, and Center for Diabetes Research, Indiana University School of Medicine, Indianapolis, Indiana nmorralc@iu.edu.
authors.forename: Núria
authors.initials: N
authors.lastname: Morral
mesh_terms: D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000378:metabolism*; D005508:Food Deprivation / Q000502:physiology; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D023421:Models, Animal; D010084:Oxidation-Reduction
chemical_list: D005227:Fatty Acids; D002334:Carnitine O-Palmitoyltransferase
keywords: carnitine palmitoyltransferase 1a; energy homeostasis; food intake; liver; metabolic control of eating