Cytokine regulation of skeletal muscle fatty acid metabolism: effect of interleukin-6 and tumor necrosis factor-alpha.
IL-6 and TNF-alpha have been associated with insulin resistance and type 2 diabetes. Furthermore, abnormalities in muscle fatty acid (FA) metabolism are strongly associated with the development of insulin resistance. However, few studies have directly examined the effects of either IL-6 or TNF-alpha on skeletal muscle FA metabolism. Here, we used a pulse-chase technique to determine the effect of IL-6 (50-5,000 pg/ml) and TNF-alpha (50-5,000 pg/ml) on FA metabolism in isolated rat soleus muscle. IL-6 (5,000 pg/ml) increased exogenous and endogenous FA oxidation by approximately 50% (P < 0.05) but had no effect on FA uptake or incorporation of FA into endogenous lipid pools. In contrast, TNF-alpha had no effect on FA oxidation but increased FA incorporation into diacylglycerol (DAG) by 45% (P < 0.05). When both IL-6 (5,000 pg/ml) and insulin (10 mU/ml) were present, IL-6 attenuated insulin's suppressive effect on FA oxidation, increasing exogenous FA oxidation (+37%, P < 0.05). Furthermore, in the presence of insulin, IL-6 reduced the esterification of FA to triacylglycerol by 22% (P < 0.05). When added in combination with IL-6 or leptin (10 microg/ml), the TNF-alpha-induced increase in DAG synthesis was inhibited. In conclusion, the results demonstrate that IL-6 plays an important role in regulating fat metabolism in muscle, increasing rates of FA oxidation, and attenuating insulin's lipogenic effects. In contrast, TNF-alpha had no effect on FA oxidation but increased FA incorporation into DAG, which may be involved in the development of TNF-alpha-induced insulin resistance in skeletal muscle.
Bruce
Clinton R
CR
Department of Human Biology and Nutritional Sciences, University of Guelph, ON, Canada N1G 2W1. crbruce@uoguelph.ca
Dyck
David J
DJ
D000818:Animals; D016207:Cytokines / Q000494:pharmacology*; D004075:Diglycerides / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D066298:In Vitro Techniques; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000494:pharmacology*; D007700:Kinetics; D020738:Leptin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010168:Palmitates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016207:Cytokines; D004075:Diglycerides; D005227:Fatty Acids; D015850:Interleukin-6; D020738:Leptin; D010168:Palmitates; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha