Intramuscular lipids, including ceramide, might be responsible for the development of insulin resistance. Insulin action is also inversely associated with circulating proinflammatory cytokines, like interleukin (IL)-18 and positively related to antiinflammatory factors, like adiponectin and IL-10. The aim of the present study was to estimate the relationships between serum adiponectin, IL-10 and IL-18 concentrations and muscle lipid fractions in healthy humans.
The study group consisted of 37 male subjects with normal glucose tolerance, without morbid obesity or other serious medical problems. Euglycemic hyperinsulinemic clamp and a biopsy of vastus lateralis muscle were performed. Muscle ceramide, sphingosine and sphinganine content and the activities of the enzymes: neutral and acid sphingomyelinase, neutral and alkaline ceramidase and serine palmitoyltransferase were measured. Muscle free fatty acid (FFA), diacylglycerol (DAG) and triacylglycerol (TG) content was also assessed.
Insulin sensitivity was related to circulating cytokines (adiponectin, r=0.38, P=0.021; IL-10, r=0.47, P=0.0034; IL-18, r=−0.37, P=0.023) and to muscle lipids (ceramide, r=−0.45, P=0.024; DAG, r=−0.43, P=0.031; TG, r=−0.52; P=0.01). It was also associated with the activities of the enzymes regulating ceramide metabolism (serine palmitoyltransferase, r=−0.58, P=0.002; alkaline ceramidase, r=−0.37, P=0.025). Adiponectin was negatively related to muscle ceramide content (r=−0.44, P=0.027) and to serine palmitoyltransferase activity (r=−0.35, P=0.032). IL-10 and IL-18 were associated, in an opposite manner, with muscle DAG (IL-10, r=−0.46, P=0.022; IL-18, r=0.40, P=0.049) and muscle TG (IL-10, r=−0.50, P=0.014; IL-18, r=0.46, P=0.026). IL-10 was also related to muscle FFA pool (r=−0.51, P=0.026).
We conclude that there are multiple associations between circulating cytokines and muscle lipid pool, which possibly might influence insulin sensitivity. Adiponectin is related to muscle ceramide content, mostly through an association with de novo synthesis pathway. IL-10 and IL-18 are associated with muscle FFA-DAG-TG pathway.