The role of resistin in obesity and insulin resistance in humans is controversial. Therefore, resistin protein was quantitated by ELISA in serum of 27 lean [13 women/14 men, body mass index (BMI) 21.7 +/- 0.4 kg/m(2), age 33 +/- 2 yr] and 50 obese (37 women/13 men, BMI 49.8 +/- 1.5 kg/m(2), age 47 +/- 1 yr) subjects. There was more serum resistin protein in the obese (mean +/- SEM: 5.3 +/- 0.4 ng/ml; range 1.8-17.9) than lean subjects (3.6 +/- 0.4 ng/ml; range 1.5-9.9; P = 0.001). The elevation of serum resistin in obese humans was confirmed by Western blot as was expression of resistin protein in human adipose tissue and isolated adipocytes. There was a significant positive correlation between resistin and BMI (r = 0.37; P = 0.002). Multiple regression analysis with predictors BMI and resistin explained 25% of the variance in homeostasis model assessment of insulin resistance score. BMI was a significant predictor of insulin resistance (P = 0.0002), but resistin adjusted for BMI was not (P = 0.11). The data demonstrate that resistin protein is present in human adipose tissue and blood, and that there is significantly more resistin in the serum of obese subjects. Serum resistin is not a significant predictor of insulin resistance in humans.

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Objective: Adiponectin mRNA expression in isolated subcutaneous and omental adipocytes was examined across a wide range of adiposity to determine whether adiponectin synthesis is impaired in these adipose tissue depots in obese humans. Tumor necrosis factor (TNF)␣ and dexamethasone were tested for inhibitory effects on adiponectin release from human adipocytes in vitro. Research Methods and Procedures: Adipocytes were isolated by collagenase digestion of abdominal adipose tissue obtained from subjects undergoing surgical procedures or outpatient needle biopsy. Adiponectin and leptin mRNA were quantitated by real-time reverse transcriptase-polymerase chain reaction. Adiponectin and leptin secretion from isolated adipocytes treated with dexamethasone or TNF␣ were determined by radioimmunoassay. Results: There was a significant negative correlation between adiponectin gene expression and BMI in subcutaneous adipocytes from 32 women (r ϭ 0.420; p ϭ 0.02). Adiponectin mRNA was also significantly correlated with serum adiponectin (r ϭ 0.44; p ϭ 0.03; n ϭ 25). There was no correlation between adiponectin mRNA expression and BMI in omental adipocytes from 29 women. Leptin mRNA was significantly and positively correlated (r ϭ 0.484; p ϭ 0.01) with BMI in the same omental adipocyte mRNA preparations. In subcutaneous adipocytes from lean subjects, TNF␣ inhibited adiponectin release by 7.4 Ϯ 1.2% (n ϭ 9, p Ͻ 0.05) but had no effect on adiponectin release from subcutaneous or omental adipocytes from obese subjects. Dexamethasone significantly inhibited adiponectin release with 24 hours of treatment. Discussion: The data suggest that reduced adiponectin synthesis in subcutaneous adipocytes contributes to lower serum adiponectin levels in obesity and that glucocorticoids regulate adiponectin gene expression in human adipocytes. TNF␣ does not seem to directly inhibit adiponectin synthesis in human adipocytes.

Resistin is an adipokine with putative prodiabetogenic properties. Like other hormones secreted by adipose tissue, resistin is being investigated as a possible etiologic link between excessive adiposity and insulin resistance. Although there is growing evidence that circulating levels of this adipokine are proportional to the degree of adiposity, an effect on insulin resistance in humans remains unproven. To evaluate the relations among resistin, obesity, and insulin resistance, we measured fasting serum resistin levels in 113 nondiabetic (75-g oral glucose tolerance test) Pima Indians (ages 29 +/- 7 years, body fat 31 +/- 8%, resistin 3.7 +/- 1.1 ng/ml [means +/- SD]), who were characterized for body composition (assessed by hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M; assessed by hyperinsulinemic clamp), basal hepatic glucose output (BHGO) and hepatic glucose output during low-dosage insulin infusion of a hyperinsulinemic clamp (HGO; a measure of hepatic insulin resistance), and acute insulin secretory response (AIR; assessed by 25-g intravenous glucose tolerance test). Follow-up measurements of M, BHGO, HGO, and AIR were available for 34 subjects who had normal glucose tolerance at baseline and remained nondiabetic at follow-up. The average time to follow-up was 4.5 +/- 2.7 years. In cross-sectional analyses, serum resistin levels were positively associated with percent body fat (r = 0.37, P = 0.0001) and 2-h glucose (r = 0.19, P = 0.04), respectively. Serum resistin levels were not associated with fasting glucose and insulin levels, M, BHGO, HGO, or AIR (r = 0.17, 0.12, -0.13, -0.06, -0.03, and -0.04, respectively; all P > 0.05). After adjusting for percent body fat, there was no association between serum resistin levels and 2-h glucose (r = 0.06, P = 0.6). In prospective analyses, high serum resistin levels at baseline were not associated with a decline in M (r = -0.1, P > 0.5). Resistin levels were, however, associated with increases in percent body fat, fasting plasma insulin, and HGO (r = 0.34, 0.36, and 0.37; all P < 0.05) after adjusting for sex, age, and time to follow-up. After additional adjustment for the change in percent body fat, there was no association between baseline serum resistin levels and changes in plasma insulin or HGO (r = 0.26 and 0.23; both P > 0.1). We conclude that in Pima Indians, like other human populations, circulating resistin levels are proportional to the degree of adiposity, but not the degree of insulin resistance. We unexpectedly found that high serum resistin levels do predict future increases in percent body fat. Our data suggest that resistin promotes obesity but not obesity-associated insulin resistance in humans.