Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice

Amanda E Brandon; Ella Stuart; Simon J Leslie; Kyle L Hoehn; David E James; Edward W Kraegen; Nigel Turner; Gregory J Cooney

doi:10.1530/JOE-15-0444

Minimal impact of age and housing temperature on the metabolic phenotype of Acc2-/- mice

J Endocrinol. 2016 Mar;228(3):127-34. doi: 10.1530/JOE-15-0444. Epub 2015 Dec 14.

Authors

Amanda E Brandon¹, Ella Stuart², Simon J Leslie², Kyle L Hoehn², David E James², Edward W Kraegen¹, Nigel Turner², Gregory J Cooney³

Affiliations

¹ 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.
² 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.
³ 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.

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.

Keywords: acetyl CoA carboxylase; energy balance; glucose metabolism; insulin resistance; metabolism.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyl-CoA Carboxylase / deficiency
Acetyl-CoA Carboxylase / physiology*
Aging / physiology*
Animals
Body Composition
Body Weight
Energy Metabolism
Fatty Acids / metabolism
Glucose Clamp Technique
Glucose Tolerance Test
Glycogen / analysis
Housing, Animal*
Insulin / blood
Male
Mice
Mice, Knockout
Muscle, Skeletal / chemistry
Muscle, Skeletal / metabolism
Oxidation-Reduction
Phenotype
Temperature*
Triglycerides / analysis

Substances

Fatty Acids
Insulin
Triglycerides
Glycogen
Acacb protein, mouse
Acetyl-CoA Carboxylase

Abstract

Publication types

MeSH terms

Substances

Grants and funding