title: Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice.
abstract: An important regulator of fatty acid oxidation (FAO) is the allosteric inhibition of CPT-1 by malonyl-CoA produced by the enzyme acetyl-CoA carboxylase 2 (ACC2). Initial studies suggested that deletion of Acc2 (Acacb) increased fat oxidation and reduced adipose tissue mass but in an independently generated strain of Acc2 knockout mice we observed increased whole-body and skeletal muscle FAO and a compensatory increase in muscle glycogen stores without changes in glucose tolerance, energy expenditure or fat mass in young mice (12-16 weeks). The aim of the present study was to determine whether there was any effect of age or housing at thermoneutrality (29 °C; which reduces total energy expenditure) on the phenotype of Acc2 knockout mice. At 42-54 weeks of age, male WT and Acc2(-/-) mice had similar body weight, fat mass, muscle triglyceride content and glucose tolerance. Consistent with younger Acc2(-/-) mice, aged Acc2(-/-) mice showed increased whole-body FAO (24 h average respiratory exchange ratio=0.95±0.02 and 0.92±0.02 for WT and Acc2(-/-) mice respectively, P<0.05) and skeletal muscle glycogen content (+60%, P<0.05) without any detectable change in whole-body energy expenditure. Hyperinsulinaemic-euglycaemic clamp studies revealed no difference in insulin action between groups with similar glucose infusion rates and tissue glucose uptake. Housing Acc2(-/-) mice at 29 °C did not alter body composition, glucose tolerance or the effects of fat feeding compared with WT mice. These results confirm that manipulation of Acc2 may alter FAO in mice, but this has little impact on body composition or insulin action.
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Brandon
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Ella
authors.initials: E
authors.lastname: Stuart
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Leslie
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Hoehn
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: David E
authors.initials: DE
authors.lastname: James
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Kraegen
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Nigel
authors.initials: N
authors.lastname: Turner
authors.affiliation: Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia Diabetes and Metabolism DivisionGarvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, AustraliaSt Vincent's Clinical SchoolUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Medical SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Biotechnology and Biomolecular SciencesUniversity of New South Wales Australia, Sydney, New South Wales, AustraliaSchool of Molecular Bioscience and Sydney Medical SchoolCharles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia g.cooney@garvan.org.au.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cooney
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000172:deficiency / Q000502:physiology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001823:Body Composition; D001835:Body Weight; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000032:analysis; D006799:Housing, Animal; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D010641:Phenotype; D013696:Temperature; D014280:Triglycerides / Q000032:analysis
chemical_list: D005227:Fatty Acids; D007328:Insulin; D014280:Triglycerides; D006003:Glycogen; C498191:Acacb protein, mouse; D000103:Acetyl-CoA Carboxylase
keywords: acetyl CoA carboxylase; energy balance; glucose metabolism; insulin resistance; metabolism