Differential Effects of Two Types of Obesity on Ketone Body Utilization in Skeletal Muscle

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Previously, we showed that obesity affects the gene expression of acetoacetyl-CoA synthetase (AACS), the enzyme responsible for the utilization of ketone bodies for lipid synthesis, in adipocytes. Therefore, we examined whether obesity also changes the AACS level in skeletal muscle. AACS mRNA expression was decreased in the skeletal muscle of leptin-deficiency-induced obese rats. In undifferentiated C2C12 myoblast cells, a high concentration of glucose induced the expression of AACS mRNA but decreased the AACS level in differentiated C2C12 cells. Moreover, leptin directly increased the AACS mRNA level in C2C12 myocytes. The expression level of succinyl-CoA: 3-oxoacid CoA-transferase (SCOT), another enzyme that induces ketone body consumption, was not changed in C2C12 cells. Our results suggest that AACS gene expression is differently affected by leptin and glucose during muscle differentiation and leptin plays a regulatory role not only in lipid consumption but also in ketone body utilization via AACS in skeletal muscle.