Potential Mechanism(s) of Obesity-Induced Insulin Resistance in Skeletal Muscle: The Role of Exercise

초록

The prevalence of obesity has reached epidemic proportions in the United States as well as South Korea, and is threatening to become a global epidemic. In modern society, obesity induced by high calorie/fat diet and reduced physical activity results in a serious health threat because of the increased risk of developing chronic diseases such as cardiovascular disease and diabetes, which are associated with insulin resistance. Skeletal muscle in our body plays an important role in regulating whole-body homeostasis; a) skeletal muscle is responsible for ~80% of the post-prandial (after a meal) clearance of glucose. b) skeletal muscle fatty acid oxidation comprises approximately 90% of energy requirements in the rested state. Once free fatty acids enter the skeletal muscle through fatty acid translocase (FAT/CD36) and fatty acid binding protein (FABP), they are activated by the enzyme, long-chain acyl-CoA synthethase (ACSL) to form an fatty acyl-CoA (FA-CoA), which then is partitioned toward the synthesis of intramyocellular lipid (IMCL) in the cytoplasm or toward mitochondria for oxidation. Obesity-induced insulin resistance in skeletal muscle is a multifactorial process. So far, it is not clear what specific mechanism(s) are responsible for obesity-induced insulin resistance. However, a number of contributing factors have been suggested. The following discussion will highlight some potential mechanisms of obesity-induced insulin resistance in skeletal muscle in terms of mitochondrial role in the cells: 1) mitochondrial-independent mechanisms and 2) mitochondrial-dependent mechanisms.