Abstract
The concept of “metabolic inflexibility” was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a key component of the metabolic syndrome, but the underlying mechanisms have remained elusive. This study identifies an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance.
Key Findings
- Comprehensive metabolic profiling links CrAT to whole body glucose homeostasis
- Muscle-specific ablation of CrAT disrupts systemic glucose tolerance in mice
- CrAT deficiency disrupts nutrient control of PDH activity and substrate switching
- L-carnitine supplements improve glucose control in insulin-resistant humans
Citation
- Muoio DM, Noland RC, Kovalik JP, Seiler SE, Davies MN, Debaisi KL, Ilkayeva OR, Stevens RD, Kheterpal I, Zhang J, Covington JD, Bajpeyi S, Ravussin E, Kraus W, Koves TR and Mynatt RL. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility. Cell Metabolism 15:764-777, 2012. PMID: 22560225. PMCID: PMC3348515.
Read More: Cell Metabolism
Research Details
- Research Center: Pennington Biomedical Research Center
- Center Contribution: The mice used in this study were made by the Transgenic Core and the project heavily relied on the services of the Animal Phenotyping component of the Animal Models and Phenotyping Core.