Cited by 158Metabolism, Diabetes, and CancerAdipose Tissue and MetabolismPeroxisome Proliferator-Activated Receptors

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Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity

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Hoehn, Kyle L., Turner, Nigel, Swarbrick, Michael M., Wilks, Donna, Preston, Elaine, Phua, Yuwei, Joshi, Himani, Furler, Stuart M., Larance, Mark, Hegarty, Bronwyn D., Leslie, Simon J., Pickford, Russell, Hoy, Andrew J., Kraegen, Edward W., James, David E., Cooney, Gregory J.·2010·Cell Metabolism

DOI 10.1016/j.cmet.2009.11.008PMC PMC2824926

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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.

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Self-citation

Authors: Hoehn, K. L., Turner, N., Swarbrick, M. M., Wilks, D., Preston, E., Phua, Y., Joshi, H., Furler, S. M., Larance, M., Hegarty, B. D., Leslie, S. J., Pickford, R., Hoy, A. J., Kraegen, E. W., James, D. E., & Cooney, G. J.
Affiliations: Garvan Institute of Medical Research (AU)
UNSW Sydney (AU)
Corresponding author: James, David E.
ORCID: Hoehn, Kyle L.
Turner, Nigel
Swarbrick, Michael M.
Larance, Mark
Hegarty, Bronwyn D.
Pickford, Russell
Hoy, Andrew J.
James, David E.
Cooney, Gregory J.
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2010-01
Volume: 11
Issue: 1
Pages: 70-76
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2009.11.008
PMC: PMC2824926
OpenAlex: W2084320367
Cited by: 156
References: 23
Citations by year: 2026: 2 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 8 · 2019: 8 · 2018: 8 · 2017: 7 · 2016: 15 · 2015: 12 · 2014: 14 · 2013: 13 · 2012: 18
FWCI: 7.82
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 1293 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (R01DK067509, DK-067509, F32DK075249)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords: mitochondrial fatty acid oxidation, AMPK, acetyl-CoA carboxylase 2, energy expenditure, adiposity, weight loss, negative energy balance, physical activity
MeSH terms: Acetyl-CoA Carboxylase, Animals, Energy Metabolism, Fatty Acids, Mitochondria, Oxidation-Reduction, Up-Regulation, Adiposity, Mice, AMP-Activated Protein Kinases

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Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity

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