Suppression of ACSL6 in Skeletal Muscle Induces Alteration of Glucose Metabolism

Abstract

Understanding the role of various sources of fatty acids and genes involved in fatty acid metabolism provide core information how nutrition therapy can be applied to the people who has different metabolic trait or genetic variance in susceptibility of metabolic diseases. Numerous isoforms of long chain acyl‐CoA synthetase (ACSL) mediate intracellular fatty acids channeling and regulate energy metabolism. However the role of these genes in skeletal muscle need to be identified in order to understand how they contribute to whole body energy metabolism. The purpose of this study was to identify a role of ACSL6 in skeletal muscle energy metabolism. C2C12 mouse myoblasts were cultured and expression of genes that involving glucose and fatty acids metabolism were analyzed. Also siRNA mediated knockdown of ACSL6 was performed to characterize the role of ACSL6 in skeletal muscle. In mouse skeletal muscle cells mRNA and protein expression of ACSL6 were increased over the time course of cellular differentiation. ACSL6 was up‐regulated by high‐glucose but its expression was not influenced by insulin treatment. Knockdown of ACSL6 decreased glucose without affecting insulin signaling or mitochondrial beta oxidation suggesting that ACSL6 is involved in glucose uptake or utilization independent of early stage of insulin signaling. On‐going study to investigate the effect of tissue specific knockdown of ACSL6 on glucose uptake and insulin signaling pathway in animal model will provide further insight into the role of ACSL6 in skeletal muscle.This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1019253