Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity
and insulin resistance.
Kern, Philip A., 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
APStracts 8:0022E, 2001.
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 = «minus»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 = «minus»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 expressed at higher levels in
subjects with obesity-related insulin resistance.
Received 1 August 2000; accepted in final form 23 January 2001
APS Manuscript Number E363-0.
Article publication pending Am J Physiol Endocrinol Metab
ISSN 1080-4757 Copyright 2001 The American Physiological Society.
Published in APStracts on 27 February 2001