title: Fatty acid oxidation and control of food intake.
abstract: Fatty acid oxidation is thought to play a role in the control of food intake, and a low postprandial oxidation of ingested fat may contribute to the overeating on a high-fat diet. Evidence for a role of fatty acid oxidation in control of food intake is mainly derived from the stimulation of feeding in response to administration of the acyl-CoA-dehydrogenase inhibitor mercaptoacetate (MA) and other inhibitors of fatty acid oxidation in different species (rat, mouse, man). Denervation studies suggest that this "lipoprivic feeding" is related to changes in hepatic fatty acid oxidation. In contrast to the strong case for a feeding stimulatory effect of an inhibition of fatty acid oxidation, the evidence for a feeding suppressive effect of a stimulation of fatty acid oxidation is inconsistent and comparatively weak. Ingestion of medium-chain fatty acids (MCFA) and peripheral administration of substances known to increase fatty acid oxidation, such as the fatty acid synthase inhibitor C75 and beta3-adrenergic agonists, decrease feeding. Yet, these substances also reduce the rats' usual preference for saccharin solution, indicating that the feeding suppressive effect is not only due to a stimulation of fatty acid oxidation. A possible approach to answer the question of whether a stimulation of hepatic fatty acid oxidation enhances satiety is to selectively increase expression and activity of the enzyme CPT 1alpha in the liver. CPT 1alpha transfers long-chain fatty acids in the cytosol from CoA to carnitine, which is the precondition for the entry of long-chain fatty acids into mitochondria and the rate-controlling step in mitochondrial fatty acid oxidation. The generation of rats with inducible, liver-specific overexpression of CPT 1alpha should permit to critically examine the putative contribution of hepatic fatty acid oxidation to the control of food intake.
authors.affiliation: Institute of Animal Sciences, Swiss Federal Institute of Technology, Schorenstr. 16, CH-8603 Schwerzenbach, Switzerland. monika.leonhardt@inw.agrl.ethz.ch
authors.forename: Monika
authors.initials: M
authors.lastname: Leonhardt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D042964:Acyl-CoA Dehydrogenase / Q000037:antagonists & inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000502:physiology; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000494:pharmacology; D013864:Thioglycolates / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D005227:Fatty Acids; D011412:Propanolamines; D013864:Thioglycolates; C017487:2-mercaptoacetate; D042964:Acyl-CoA Dehydrogenase; C033394:CGP 12177; D020155:3-Hydroxybutyric Acid