title: Acute or chronic upregulation of mitochondrial fatty acid oxidation has no net effect on whole-body energy expenditure or adiposity.
abstract: Activation of AMP-activated protein kinase (AMPK) is thought to convey many of the beneficial effects of exercise via its inhibitory effect on acetyl-CoA carboxylase 2 (ACC2) and promotion of fatty acid oxidation. Hence, AMPK and ACC have become major drug targets for weight loss and improved insulin action. However, it remains unclear whether or how activation of the fatty acid oxidation pathway without a concomitant increase in energy expenditure could be beneficial. Here, we have used either pharmacological (administration of the AMPK agonist 5(') aminoimidazole-4-carboxamide-riboside) or genetic means (mutation of the ACC2 gene in mice) to manipulate fatty acid oxidation to determine whether this is sufficient to promote leanness. Both of these strategies increased whole-body fatty acid oxidation without altering energy expenditure or adiposity. We conclude that negative energy balance is a prerequisite for weight reduction, and increased fatty acid oxidation per se has little, if any, effect to reduce adiposity.
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
authors.forename: Michael M
authors.initials: MM
authors.lastname: Swarbrick
authors.forename: Donna
authors.initials: D
authors.lastname: Wilks
authors.forename: Elaine
authors.initials: E
authors.lastname: Preston
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Phua
authors.forename: Himani
authors.initials: H
authors.lastname: Joshi
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Furler
authors.forename: Mark
authors.initials: M
authors.lastname: Larance
authors.forename: Bronwyn D
authors.initials: BD
authors.lastname: Hegarty
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Leslie
authors.forename: Russell
authors.initials: R
authors.lastname: Pickford
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Hoy
authors.forename: Edward W
authors.initials: EW
authors.lastname: Kraegen
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cooney
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000502:physiology*; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D015854:Up-Regulation
chemical_list: D005227:Fatty Acids; D055372:AMP-Activated Protein Kinases; C498191:Acacb protein, mouse; D000103:Acetyl-CoA Carboxylase