Novel role of carnitine in skeletal muscle revealed using dynamics analysis

Abstract

Carnitine is well recognized for transporting fatty acids across the mitochondrial membrane; however, studies conducted in the last decade have highlighted another role of carnitine in buffering the excess of mitochondrial acetyl-CoA, an intermediate metabolite of beta-oxidation and glycolytic metabolism. Although acetyl-CoA is an essential metabolite, excess accumulation of acetyl-CoA inhibits pyruvate dehydrogenase, resulting in negative regulation of glucose uptake. In this situation, carnitine binds to acetyl-CoA and is converted to acetylcarnitine, resulting in a decrease in acetyl-CoA levels. It has been demonstrated that carnitine acetylation is essential for glucose homeostasis, and that its dysfunction, caused by aging and high-fat feeding, induces metabolic failure. To analyze carnitine dynamics in skeletal muscle, we have used imaging mass spectrometry to visualize the distribution of acetylcarnitine in rodent skeletal muscle and performed tracing experiments using isotopic labeled carnitine. It was shown that carnitine uptake and acetylation were elevated in oxidative muscles, and that they were dynamically controlled by muscle contraction. Recent studies using cell culture experiments demonstrated that acetylcarnitine is exported from skeletal muscle cells. It is hypothesized that muscle carnitine acetylation in skeletal muscle is not only beneficial for buffering the excess acetyl-CoA, but also plays in the endocrine system. In fact, previous work has shown that plasma acetylcarnitine concentration increases during exercise in humans, suggesting that the acetylcarnitine produced during muscle contraction may be released from muscle cells to serve different functions. In this article, we reviewed the novel roles of carnitine in skeletal muscle by analyzing carnitine dynamics.