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
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–158 of 158
Mitochondrial regulation of insulin action
Murrow, B. A., & Hoehn, K. L. (2010) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.08.020 · Cited by 20
Self-citationDetection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification
Arch, J. R. S., & Trayhurn, P. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00064 · Cited by 20
Molecularly imprinted electrochemical sensing platform for 2-Aminoadipic acid, a diabetes biomarker
Anirudhan, T. S., Mani, A., & Athira, V. S. (2021) · Reactive and Functional Polymers · doi:10.1016/j.reactfunctpolym.2021.105056 · Cited by 19
Chen, Q., Ji, C., Zheng, R., Yang, L., Ren, J., Li, Y., Han, Y., Zhou, P., Liu, Z., & Qiu, Y. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01622 · Cited by 18
Takagi, H., Ikehara, T., Kashiwagi, Y., Hashimoto, K., Nanchi, I., Shimazaki, A., Nambu, H., & Yukioka, H. (2018) · Endocrinology · doi:10.1210/en.2018-00338 · Cited by 18
Low capacity to oxidize fat and body weight
Péronnet, F., & Haman, F. (2019) · Obesity Reviews · doi:10.1111/obr.12910 · Cited by 20
Worley, B. L., Auen, T. J., Arnold, A. C., Monia, B. P., Hempel, N., & Czyzyk, T. A. (2021) · Physiological Reports · doi:10.14814/phy2.14853 · Cited by 16
Piperazine Oxadiazole Inhibitors of Acetyl-CoA Carboxylase
Bourbeau, M. P., Siegmund, A., Allen, J. G., Shu, H., Fotsch, C. H., Bartberger, M. D., Kim, K., Komorowski, R., Graham, M., Busby, J., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm401601s · Cited by 17
Glucagon controls obesity-specific energy expenditure via persistent cAMP/PKA signaling
Long, F., Challa, T. D., Ding, L., Sharma, A. K., Wu, C., Ghosh, A., Noé, F., Horváth, C., Liebisch, G., Höring, M., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.06.011 · Cited by 17
Szkudelski, T., & Szkudelska, K. (2016) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2016.1227853 · Cited by 16
Song, K., Zhang, Y., Ga, Q., Bai, Z., & Ge, R. (2020) · Obesity Facts · doi:10.1159/000508112 · Cited by 19
Acetyl CoA carboxylase inactivation and meiotic maturation in mouse oocytes
Valsangkar, D., & Downs, S. M. (2015) · Molecular Reproduction and Development · doi:10.1002/mrd.22505 · Cited by 16
Liu, T., Gou, L., Yan, S., & Huang, T. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8700 · Cited by 15
Germline ablation of VGF increases lipolysis in white adipose tissue
Fargali, S., Scherer, T., Shin, A. C., Sadahiro, M., Buettner, C., & Salton, S. R. (2012) · Journal of Endocrinology · doi:10.1530/joe-12-0172 · Cited by 14
Takagi, H., Tanimoto, K., Shimazaki, A., Tonomura, Y., Momosaki, S., Sakamoto, S. X., Abe, K., Notoya, M., & Yukioka, H. (2020) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.263590 · Cited by 15
Tbc1d1 deletion suppresses obesity in leptin-deficient mice
Dokas, J., Chadt, A., Joost, H., & Al‐Hasani, H. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.45 · Cited by 14
Multiple AMPK activators inhibit l -carnitine uptake in C2C12 skeletal muscle myotubes
Shaw, A., Jeromson, S., Watterson, K. R., Pediani, J. D., Gallagher, I. J., Whalley, T., Dreczkowski, G., Brooks, N. E., Galloway, S. D. R., & Hamilton, D. L. (2017) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00026.2016 · Cited by 13
Huang, T., Chen, X., He, J., Zheng, P., Luo, Y., Wu, A., Yan, H., Yu, B., Chen, D., & Huang, Z. (2023) · eLife · doi:10.7554/elife.90724 · Cited by 12
Acetyl CoA Carboxylase 2 Is Dispensable for CD8+ T Cell Responses
Lee, J., Walsh, M. C., Hoehn, K. L., James, D. E., Wherry, E. J., & Choi, Y. (2015) · PLoS ONE · doi:10.1371/journal.pone.0137776 · Cited by 13
Self-citationVavrova, E., Lenoir, V., Alves‐Guerra, M., Denis, R., Castel, J., Esnous, C., Dyck, J. R. B., Luquet, S. H., METZGER, D., Bouillaud, F., et al. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00020.2016 · Cited by 14
Phenotypic Discrepancies in Acetyl-CoA Carboxylase 2-deficient Mice
Hoehn, K. L., Turner, N. A., Cooney, G. J., & James, D. E. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.o112.356915 · Cited by 11
Self-citationChemical-genetic induction of Malonyl-CoA decarboxylase in skeletal muscle
Rodriguez, S., Ellis, J. M., & Wolfgang, M. J. (2014) · BMC Biochemistry · doi:10.1186/1471-2091-15-20 · Cited by 11
Minimal impact of age and housing temperature on the metabolic phenotype of Acc2−/− mice
Brandon, A. E., Stuart, E., Leslie, S. J., Hoehn, K. L., James, D. E., Kraegen, E. W., Turner, N. A., & Cooney, G. J. (2015) · Journal of Endocrinology · doi:10.1530/joe-15-0444 · Cited by 11
Self-citationRecent Advances in Acetyl-CoA Carboxylase Inhibitors
Bourbeau, M. P., Allen, J. G., & Gu, W. (2010) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(10)45006-x · Cited by 10
The Paleo Solution: The Original Human Diet
Wolf, R. (2010) · Cited by 10
Admin, A., Presby, D. M., Rudolph, M. C., Sherk, V. D., Jackman, M. R., Foright, R. M., Jones, K. L., Houck, J. A., Johnson, G. C., HIGGINS, J. A., et al. (2021) · Diabetes · doi:10.2337/db20-0763 · Cited by 8
Guo, M., Meng, X., Zhang, T., Wang, Y., Wang, Y., Hou, N., & Zhao, X. (2025) · Chemical Engineering Journal · doi:10.1016/j.cej.2025.165606 · Cited by 6
Glucagon and lipid signaling in the hypothalamus
LaPierre, M. P., Abraham, M. A., Filippi, B., Yue, J. T. Y., & Lam, T. K. T. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9510-6 · Cited by 6
Cutting fuel offers new clues in diabetic mystery
Neufer, P. D. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.h119.010075 · Cited by 5
Isotype-selective roles of hepatic acetyl-CoA carboxylases in a mouse model of fatty liver disease
Beretta, M., Vancuylenburg, C. S., Shrestha, R., Olzomer, E. M., Osborne, B., Zhou, M., Zhang, S., Hargreaves, A., Byrne, F. L., & Hoehn, K. L. (2025) · Molecular Metabolism · doi:10.1016/j.molmet.2025.102264 · Cited by 3
Self-citationRahman, M. M., Sarker, M. T., Ahmed, S., Uddin, M. N., Islam, M. R., Islam, M. R., Das, S., Mukherjee, N., Hemeg, H. A., Rauf, A., et al. (2023) · Process Biochemistry · doi:10.1016/j.procbio.2023.07.007 · Cited by 4
Birnbaum, M. J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381510-1.00059-4 · Cited by 4
Advanced Computational Modeling Accelerating Small‐Molecule Drug Discovery
Abel, R. (2022) · Wiley eBooks · doi:10.1002/9781119627784.ch2 · Cited by 3
Fatouros, I. G., & Mitrakou, A. (2012) · CRC Press eBooks · doi:10.1201/b12085-16 · Cited by 2
Les tissus adipeux thermogéniques : un rôle dans le traitement de l’obésité ?
Langin, D. (2022) · Médecine des Maladies Métaboliques · doi:10.1016/j.mmm.2022.09.010 · Cited by 2
Reply to Hoehn et al.: Phenotypic Discrepancies in Acetyl-CoA Carboxylase 2-deficient Mice
Abu-Elheiga, L. A., Wu, H., Gu, Z., & Wakil, S. J. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.o112.362939 · Cited by 2
Huang, T., Chen, X., He, J., Zheng, P., Luo, Y., Wu, A., Yan, H., Yu, B., Chen, D., & Huang, Z. (2024) · eLife · doi:10.7554/elife.90724.3 · Cited by 1
Lee, J. Y., Zhu, C., Boldridge, M. A., Stark, R. L., Bonilla, G. M., Watari, K., Papa, C., Xu, L., Gonzãlez, F., Tang, X., et al. (2026) · Science Advances · doi:10.1126/sciadv.aed3119 · Cited by 1
Pal, A., & Rath, P. C. (2020) · Springer eBooks · doi:10.1007/978-981-32-9005-1_17 · Cited by 2
van Bree, B. W. J. (2014) · Research Publications (Maastricht University) · doi:10.26481/dis.20141017bb
Cordonier, E. L. (2015) · Lincoln (University of Nebraska)
Gavaldà, O., & María, J. (2011) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Resposta à insulina no músculo esquelético de ratos tratados com apocinina.
Fujiwara, H. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.42.2013.tde-12062013-094713
Dietary polyphenols: modulators of energy and substrate metabolism in obese humans
Most, J. (2016) · Research Publications (Maastricht University) · doi:10.26481/dis.20160115jm
Queiroz, A. L. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2017.tde-30032017-162044 · Cited by 1
Magdalon, J. (2017) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.42.2017.tde-19012017-155521
Warnke (2018) · Research Publications (Maastricht University) · doi:10.26481/dis.20180316iw
Bruls, Y. M. H. (2018) · Research Publications (Maastricht University) · doi:10.26481/dis.20180614yb
Tissue Specific Roles of Fatty Acid Oxidation
Lee, J. (2016)
Klip, A., & Pillon, N. J. (2018) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733852398.793550114
(2010) · Nature Medicine · doi:10.1038/nm0210-169
Huang, T., Chen, X., He, J., Zheng, P., Luo, Y., Wu, A., Yan, H., Yu, B., Chen, D., & Huang, Z. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.18.549410
Huang, T., Chen, X., He, J., Zheng, P., Luo, Y., Wu, A., Yan, H., Yu, B., Chen, D., & Huang, Z. (2023) · eLife · doi:10.7554/elife.90724.1
Huang, T., Chen, X., He, J., Zheng, P., Luo, Y., Wu, A., Yan, H., Yu, B., Chen, D., & Huang, Z. (2024) · eLife · doi:10.7554/elife.90724.2
Anthocyanin-Induced Alterations in Substrate Oxidation During Exercise: A Narrative Review
Cook, M. D., Bateman, J. J., & Willems, M. E. T. (2026) · Nutrients · doi:10.3390/nu18183018
BindingDB Entry 50043801: Piperazine oxadiazole inhibitors of acetyl-CoA carboxylase.
BindingDB (2014) · UC San Diego · doi:10.7270/q2ww7k5k
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
