Abstract 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 (S I ) was determined by an intravenous glucose tolerance test with minimal-model analysis. When lean body mass index (BMI) <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, and 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 obesity and insulin resistance. Plasma IL-6 was significantly higher in obese subjects and demonstrated a highly significant inverse relationship with S I ( r = −0.71, P < 0.001). To separate the effects of BMI from S I , subjects who were discordant for S I were matched for BMI, age, and gender. By use of this approach, subjects with low S I 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 S I . 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 Footnotes This study was supported by a Veterans Affairs Department Merit Review Grant M01-RR-14288 of the General Clinical Research Center, a Career Development Award from the American Diabetes Association, and DK-39176 from the National Institutes of Health. Address for reprint requests and other correspondence: P. A. Kern, Central Arkansas Veterans Healthcare System, 598/151 LR 4300 West 7th St., Little Rock, AR 72205 (E-mail: KernPhilipA@uams.edu ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Copyright © 2001 the American Physiological Society
AJP - Endocrinology and Metabolism – The American Physiological Society
Published: May 1, 2001
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