The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
Regulatory enzymes of mitochondrial β‐oxidation as targets for treatment of the metabolic syndrome
Open accessAbstract
Summary: Insulin sensitizers like metformin generally act through pathways triggered by adenosine monophosphate‐activated protein kinase. Carnitine palmitoyltransferase 1 (CPT1) controls mitochondrial β‐oxidation and is inhibited by malonyl‐CoA, the product of acetyl‐CoA carboxylase (ACC). The adenosine monophosphate‐activated protein kinase‐ACC‐CPT1 axis tightly regulates mitochondrial long‐chain fatty acid oxidation. Evidence indicates that ACC2, the isoform located in close proximity to CPT1, is the major regulator of CPT1 activity. ACC2 as well as CPT1 are therefore potential targets to treat components of the metabolic syndrome such as obesity and insulin resistance. Reversible inhibitors of the liver isoform of CPT1, developed to prevent ketoacidosis and hyperglycemia, have been found to be associated with side effects like hepatic steatosis. However, stimulation of systemic CPT1 activity may be an attractive means to accelerate peripheral fatty acid oxidation and hence improve insulin sensitivity. Stimulation of CPT1 can be achieved by elimination or inhibition of ACC2 activity and through activating transcription factors like peroxisome proliferator‐activated receptors and their protein partners. The latter leads to enhanced CPT1 gene expression. Recent developments are discussed, including a recently identified CPT1 isoform, i.e. CPT1C. This protein is highly expressed in the brain and may provide a target for new tools to prevent obesity.
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Cites
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“This shuttle provides the net transport of LC acyl-CoA across the mitochondrial membranes (2) and is facilitated by three proteins: CPT1, carnitine acylcarnitine translocase and CPT2 (2,9).”
BackgroundInfluentialRegulation of hepatic fatty acid oxidation and ketone body production
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Sirtuins as regulators of metabolism and healthspan
Houtkooper, R. H., Pirinen, E., & Auwerx, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3293 · Cited by 2,008
Role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis
Rolo, A. P., Teodoro, J. S., & Palmeira, C. M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.10.003 · Cited by 955
The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome
Lim, J. S., Mietus-Snyder, M., Valente, A., Schwarz, J.-M., & Lustig, R. H. (2010) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2010.41 · Cited by 771
Neufeld-Cohen, A., Robles, M. S., Aviram, R., Manella, G., Adamovich, Y., Ladeuix, B., Nir, D., Rousso-Noori, L., Kuperman, Y., Golik, M., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1519650113 · Cited by 262
Lim, J.-H., Gerhart-Hines, Z., Dominy, J. E., Lee, Y., Kim, S., Tabata, M., Xiang, Y. K., & Puigserver, P. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415729 · Cited by 212
Metadata
- Authors
- Schreurs, M., Kuipers, F., & Van Der Leij, F. R.
- Venue
- Obesity Reviews
- Publisher
- Wiley
- Published
- 2010-04-14
- Volume
- 11
- Issue
- 5
- Pages
- 380-388
- ISSN
- 1467-7881 (ISSN-L)
- 1467-789X
- OpenAlex
- W2127012454
- Cited by
- 296
- References
- 18
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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