The contribution of skeletal muscle tumor necrosis factor-α to insulin resistance and hypertension in fructose-fed rats

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Abstract
Objective The aim of this study was to determine the role of tumor necrosis factor-α (TNF-α) in skeletal muscle tissue in insulin resistance and hypertension and the effect of anti-hypertensive medicine on skeletal muscle TNF-α in fructose-induced insulin-resistant and hypertensive rats(fructose-fed rats: FFR). Design and methods Six-week-old male Sprague-Dawley rats were fed either normal rat chow or fructose-rich chow. For the last 2 weeks of a 6-week period of either diet, the rats were treated with a vehicle (control or FFR); temocapril, an angiotensin converting enzyme inhibitor (ACEI); or CS-866, an angiotensin II type 1 receptor blocker (ARB). The euglycemic hyperinsulinemic glucose clamp technique was performed to evaluate insulin sensitivity (M value). TNF-α levels in soleus and extensor digitorum longus (EDL) muscles and epididymal fat pads were measured. We also measured the TNF-α concentration in an incubated medium secreted from soleus muscle strips with or without angiotensin II. Results TNF-α levels were significantly higher in the soleus and EDL muscles, but not in the epididymal fat, in the FFRs compared with the control rats. Temocapril and CS-866 lowered systolic blood pressure, improved insulin resistance, and reduced TNF-α in both skeletal muscles. There were significant negative correlations between M values and TNF-α levels in both soleus and EDL muscles. Also, the soleus muscle strip incubation with 10−7 mol/l angiotensin II increased TNF-α secreted into the incubation medium compared to the incubation without angiotensin II. These results suggest that skeletal muscle TNF-α is linked to insulin resistance and hypertension and that angiotensin II may be one of the factors that regulate skeletal muscle TNF-α.