Effect of Skeletal Muscle-Specific AMP Kinase Inhibition on Exercise-Induced Quantitative and Functional Adaptations of White Adipose Tissue

Abstract

Exercise elicits quantitative and functional adaptations of white adipose tissue (WAT); however, the molecular mechanism remains unclear. AMP kinase (AMPK) in the skeletal muscle may contribute to the adaptations of WAT via enhanced fat oxidation and myokine expression. Therefore, we investigated whether AMPK in the skeletal muscle is involved in exercise-induced quantitative and functional adaptations of WAT. For skeletal muscle-specific inhibition of AMPK activity, we used transgenic mice overexpressing the dominant-negative mutant of AMPKα1 in the skeletal muscle (AMPK-DN mice). Both AMPK-DN and wild-type (WT) mice were randomly divided into two groups: wheel running groups or sedentary groups. After the four-week intervention, the body weight was measured, and the epididymal WAT was excised. The protein expression of lipolysis-related molecules, triacylglycerol synthesis-related molecules, and a mitochondrial marker were measured by western blotting. AMPK-DN mice demonstrated exercise-induced decrement of epididymal WAT weight. Furthermore, although WT mice showed an increase in the protein expression of lipolysis-related molecule perilipin 1, this increase was diminished in AMPK-DN mice. On the other hand, no significant differences between genotypes were observed in the exercise-induced response of triacylglycerol synthesis-related molecules (fatty acid synthase and stearoyl-CoA desaturase 1) and a mitochondrial marker (voltage-dependent anion channel). In conclusion, these results suggest that AMPK in the skeletal muscle contributes to exercise-induced quantitative and functional adaptations of WAT.