The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Acute or Chronic Upregulation of Mitochondrial Fatty Acid Oxidation Has No Net Effect on Whole-Body Energy Expenditure or Adiposity
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Intriguingly however, two other groups have recently generated whole body- and muscle-specific ACC2 knockout models and found no effect of the gene deletion on body weight, food intake, body composition and susceptibility to diet-induced obesity and glucose intolerance (Hoehn et al., 2010; Olson et al., 2010).”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Hoehn et al., 2010
In the citing paper
“Instead, the genetically engineered switch to fat catabolism was offset by diminished glucose oxidation and a reciprocal rise in de novo lipogenesis.”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Hoehn et al., 2010
In the citing paper
“In these second generation models total energy expenditure was either unaffected (Hoehn et al., 2010) or only slightly increased (Olson et al., 2010).”
From Lipid-Induced Mitochondrial Stress and Insulin Action in Muscle (2012) · cites this paper as Hoehn et al., 2010
In the citing paper
“Together, these data suggest that a shift in substrate preference, without an increase in total energy expenditure, will not protect against fat-induced insulin resistance.”
From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [54]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Randle, P. J., Garland, P. B., Hales, C. N., & Newsholme, E. A. (1963) · The Lancet · doi:10.1016/s0140-6736(63)91500-9 · Cited by 5,093
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity
Cantó, C., Gerhart-Hines, Z., Feige, J. N., Lagouge, M., Noriega, L., Milne, J. C., Elliott, P. J., Puigserver, P., & Auwerx, J. (2009) · Nature · doi:10.1038/nature07813 · Cited by 3,300
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α
Jäger, S., Handschin, C., St.-Pierre, J., & Spiegelman, B. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705070104 · Cited by 2,491
Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes
Kelley, D. E., He, J., Menshikova, E. V., & Ritov, V. B. (2002) · Diabetes · doi:10.2337/diabetes.51.10.2944 · Cited by 2,321
Mitochondrial dysfunction in the elderly: possible role in insulin resistance
Petersen, K. F., Befroy, D., Dufour, S., Dziura, J., Ariyan, C., Rothman, D. L., DiPietro, L., Cline, G. W., & Shulman, G. I. (2003) · Science · doi:10.1126/science.1082889 · Cited by 2,107
Koves, T. R., Ussher, J. R., Noland, R. C., Slentz, D., Mosedale, M., Ilkayeva, O., Bain, J., Stevens, R., Dyck, J. R. B., Newgard, C. B., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.013 · Cited by 1,990
AMPK and PPARδ Agonists Are Exercise Mimetics
Narkar, V. A., Downes, M., Yu, R. T., Embler, E., Wang, Y.-X., Banayo, E., Mihaylova, M. M., Nelson, M. C., Zou, Y., Juguilon, H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.06.051 · Cited by 1,222
Disordered lipid metabolism and the pathogenesis of insulin resistance.
Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007) · Physiological Reviews · doi:10.1152/physrev.00024.2006 · Cited by 1,107
Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2
Abu-Elheiga, L., Matzuk, M. M., Abo-Hashema, K. A. H., & Wakil, S. J. (2001) · Science · doi:10.1126/science.1056843 · Cited by 903
Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle
Winder, W. W., Holmes, B. F., Rubink, D. S., Jensen, E. B., Chen, M., & Holloszy, J. O. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.6.2219 · Cited by 709
Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis
Bergeron, R., Ren, J. M., Cadman, K. S., Moore, I. K., Perret, P., Pypaert, M., Young, L. H., Semenkovich, C. F., & Shulman, G. I. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.281.6.e1340 · Cited by 561
AMPK: a metabolic gauge regulating whole-body energy homeostasis
Lage, R., Diéguez, C., Vidal‐Puig, A., & López, M. (2008) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2008.09.007 · Cited by 512
Savage, D. B. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27300 · Cited by 447
Bruce, C. R., Hoy, A. J., Turner, N., Watt, M. J., Allen, T. L., Carpenter, K., Cooney, G. J., Febbraio, M. A., & Kraegen, E. W. (2009) · Diabetes · doi:10.2337/db08-1078 · Cited by 363
Self-citationChoi, C. S., Savage, D. B., Abu-Elheiga, L., Liu, Z.-X., Kim, S., Kulkarni, A., Distefano, A., Hwang, Y.-J., Reznick, R. M., Codella, R., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0706794104 · Cited by 325
MacArthur, D. G., Seto, J. T., Chan, S., Quinlan, K. G. R., Raftery, J. M., Turner, N. A., Nicholson, M. D., Kee, A. J., Hardeman, E. C., Gunning, P. W., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm380 · Cited by 289
Self-citationSuwa, M., Nakano, H., & Kumagai, S. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00349.2003 · Cited by 258
Harwood, H. J., Petras, S. F., Shelly, L. D., Zaccaro, L. M., Perry, D. A., Makowski, M. R., Hargrove, D. M., Martin, K. A., Tracey, W. R., Chapman, J. G., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304481200 · Cited by 243
Improved glucose homeostasis and enhanced insulin signalling in Grb14‐deficient mice
Cooney, G. J., Lyons, R. J., Crew, A. J., Jensen, T. E., Molero, J. C., Mitchell, C. J., Biden, T. J., Ormandy, C. J., James, D. E., & Daly, R. J. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600082 · Cited by 132
Self-citationReduced body weight is a common effect of gene knockout in mice
Reed, D. R., Lawler, M. P., & Tordoff, M. G. (2008) · BMC Genetics · doi:10.1186/1471-2156-9-4 · Cited by 98
Hoy, A. J., Bruce, C. R., Cederberg, A., Turner, N. A., James, D. E., Cooney, G. J., & Kraegen, E. W. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00133.2007 · Cited by 56
Self-citationMinkler, P. E., Kerner, J., Kasumov, T., Parland, W., & Hoppel, C. L. (2006) · Analytical Biochemistry · doi:10.1016/j.ab.2006.02.015 · Cited by 39
Review of recent acetyl-CoA carboxylase inhibitor patents: mid-2007 – 2008
Corbett, J. W. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902862180 · Cited by 34
Cited by
Sorted by citations
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Lipid-induced insulin resistance: unravelling the mechanism
Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60408-4 · Cited by 1,189
Fullerton, M. D., Galic, S., Marcinko, K., Sikkema, S., Pulinilkunnil, T., Chen, Z.-P., O'Neill, H. M., Ford, R. J., Palanivel, R., O'Brien, M., et al. (2013) · Nature Medicine · doi:10.1038/nm.3372 · Cited by 893
Guo, S. (2013) · Journal of Endocrinology · doi:10.1530/joe-13-0327 · Cited by 648
Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association
Bays, H. E., Toth, P. P., Kris-Etherton, P. M., Abate, N., Aronne, L. J., Brown, W. V., Gonzalez-Campoy, J. M., Jones, S. R., Kumar, R., La Forge, R., et al. (2013) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.04.001 · Cited by 521
Metadata
- 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
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 11
- Issue
- 1
- Pages
- 70-76
- ISSN
- 1550-4131 (ISSN-L)
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
