Carnitine palmitoyltransferase 2 (CPT2) knockout potentiates palmitate-induced insulin resistance in C2C12 myotubes.

Carnitine palmitoyltransferase 2 (CPT2) knockout potentiates palmitate-induced insulin resistance in C2C12 myotubes. Am J Physiol Endocrinol Metab. 2020 May 27;: Authors: Blackburn ML, Ono-Moore K, Sobhi HF, Adams SH Abstract Saturated fatty acids (SFAs) are implicated in muscle inflammation/cell stress and insulin resistance, but the catalog of factors involved is incomplete. SFA derivatives that accumulate with mismatched FA availability and FA oxidation (FAO) are likely involved, and evidence has emerged that select acylcarnitines should be considered. To understand if excessive long-chain acylcarnitine accumulation and limited FAO associate with lipotoxicity, carnitine palmitoyltransferase 2 knockout C2C12 cells were generated (CPT2 KO). CPT2 KO was confirmed by Western blot, increased palmitoylcarnitine accumulation and loss of FAO capacity. There was no effect of CPT2 KO on palmitic acid (PA) concentration-dependent increases in media IL-6 or adenylate kinase. PA at (200, 500 µM) did not trigger cell stress responses (phospho-Erk, -JNK, or -p38) above that of vehicle in WT or CPT2 KO cells. In contrast, loss of CPT2 exacerbated PA-induced insulin resistance (acute phospho-Akt; 10 or 100 nM insulin) by as much as ~50-96% compared to WT. Growing cells in carnitine-free media abolished differences between WT and CPT2 KO. The results suggest that PA-induced insulin resistance stems in part from palmitoylcarnitine accumulation, alb...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research