Adipose tissue tumor necrosis factor and interleukin-6 expression in humanobesity and insulin resistance

Adipose tissue expresses tumor necrosis factor (TNF) and interleukin (IL)-6 , which may cause obesity-related insulin resistance. We measured TNF and I L-6 expression in the adipose tissue of 50 lean and obese subjects without diabetes. Insulin sensitivity (SI) was determined by an intravenous glucose tolerance test with minimal-model analysis. When lean [body mass index (BM I) <25 kg/m(2)] and obese (BMI 30-40 kg/m(2)) subjects were compared, there was a 7.5-fold increase in TNF secretion (P < 0.05) from adipose tissue, a nd the TNF secretion was inversely related to S-I (r = -0.42, P < 0.02). IL -6 was abundantly expressed by adipose tissue. In contrast to TNF, plasma ( rather than adipose) IL-6 demonstrated the strongest relationship with obes ity and insulin resistance. Plasma IL-6 was significantly higher in obese s ubjects and demonstrated a highly significant inverse relationship with SI (r = -0.71, P < 0.001). To separate the effects of BMI from Sr, subjects wh o were discordant for SI were matched for BMI, age, and gender. By use of t his approach, subjects with low SI demonstrated a 3.0-fold increased level of TNF secretion from adipose tissue and a 2.3-fold higher plasma IL-6 leve l (P < 0.05) compared with matched subjects with a high SI. Plasma IL-6 was significantly associated with plasma nonesterified fatty acid levels (r = 0.49, P < 0.002). Thus the local expression of TNF and plasma IL-6 are high er in subjects with obesity-related insulin resistance.