| First Author | Pereyra AS | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 6 | Pages | 108374 |
| PubMed ID | 33176143 | Mgi Jnum | J:298894 |
| Mgi Id | MGI:6489201 | Doi | 10.1016/j.celrep.2020.108374 |
| Citation | Pereyra AS, et al. (2020) Loss of Muscle Carnitine Palmitoyltransferase 2 Prevents Diet-Induced Obesity and Insulin Resistance despite Long-Chain Acylcarnitine Accumulation. Cell Rep 33(6):108374 |
| abstractText | To assess the effects of acylcarnitine accumulation on muscle insulin sensitivity, a model of muscle acylcarnitine accumulation was generated by deleting carnitine palmitoyltransferase 2 (CPT2) specifically from skeletal muscle (Cpt2(Sk-/-) mice). CPT2 is an irreplaceable enzyme for mitochondrial long-chain fatty acid oxidation, converting matrix acylcarnitines to acyl-CoAs. Compared with controls, Cpt2(Sk-/-) muscles do not accumulate anabolic lipids but do accumulate approximately 22-fold more long-chain acylcarnitines. High-fat-fed Cpt2(Sk-/-) mice resist weight gain, adiposity, glucose intolerance, insulin resistance, and impairments in insulin-induced Akt phosphorylation. Obesity resistance of Cpt2(Sk-/-) mice could be attributed to increases in lipid excretion via feces, GFD15 production, and energy expenditure. L-carnitine supplement intervention lowers acylcarnitines and improves insulin sensitivity independent of muscle mitochondrial fatty acid oxidative capacity. The loss of muscle CPT2 results in a high degree of long-chain acylcarnitine accumulation, simultaneously protecting against diet-induced obesity and insulin resistance. |
