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Am J Physiol Endocrinol Metab 280: E745-E751, 2001;
0193-1849/01 $5.00
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Vol. 280, Issue 5, E745-E751, May 2001

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

Philip A. Kern, Subramanian Ranganathan, Chunling Li, Linda Wood, and Gouri Ranganathan

Division of Endocrinology, Department of Medicine, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205

Adipose tissue expresses tumor necrosis factor (TNF) and interleukin (IL)-6, which may cause obesity-related insulin resistance. We measured TNF and IL-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 (BMI) <25 kg/m2] and obese (BMI 30-40 kg/m2) subjects were compared, there was a 7.5-fold increase in TNF secretion (P < 0.05) from adipose tissue, and the TNF secretion was inversely related to SI (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 obesity and insulin resistance. Plasma IL-6 was significantly higher in obese subjects and demonstrated a highly significant inverse relationship with SI (r = -0.71, P < 0.001). To separate the effects of BMI from SI, subjects who were discordant for SI were matched for BMI, age, and gender. By use of this 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 level (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 higher in subjects with obesity-related insulin resistance.

type 2 diabetes


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