Capric Acid Attenuates Palmitate-Induced Lipotoxicity and Metabolic Dysfunction in Skeletal Muscle Cells.
TL;DR
It is suggested that C10 attenuates palmitate-induced muscle dysfunction by promoting lipid, metabolic, and structural remodeling in C2C12 myotubes.
Abstract
Skeletal muscle insulin resistance and atrophy are associated with lipid overload and lipotoxicity. The effects of medium-chain fatty acids on skeletal muscle lipotoxicity are unclear. Here, we investigated the effects of capric acid (C10) on palmitate-induced dysfunction in C2C12 myotubes by evaluating their morphology, lipid accumulation, contractile activity, and insulin signaling, and performing lipidomic and proteomic analyses. Palmitate increased lipid droplet accumulation, impaired myotube integrity and contractility, and reduced insulin-stimulated Akt phosphorylation. Concurrent C10 treatment suppressed lipid accumulation and restored myotube morphology, contractile activity, and insulin responsiveness. Lipidomic analyses revealed that C10 reduced palmitate-containing ceramide and triacylglycerol species while increasing C10-containing triacylglycerols. Proteomics revealed the enrichment of cytoskeletal, motor protein, glycolytic, and tricarboxylic acid cycle pathways and downregulation of diabetic cardiomyopathy-related pathways. Furthermore, C10 pre-treatment partially protected against palmitate-induced dysfunction. These findings suggest that C10 attenuates palmitate-induced muscle dysfunction by promoting lipid, metabolic, and structural remodeling.