Background: Tumour necrosis factor alpha (TNF) mRNA expression has been reported to be up-regulated in adipose tissue from several rodent models of obesity and diabetes and from obese humans. This elevated expression has been assumed to be associated with the development of insulin resistance. However, the biological signal of TNF may be influenced by the expression of the two TNF receptors: the p60 TNF receptor, TNFR60, and the p80 TNF receptor, TNFR80.
Design: The aim of this study was to investigate the mRNA expression pattern of the two TNF receptors and their ligand in two adipose tissue depots of glucose-tolerant obese women [n = 18, body mass index (BMI) 48.2 +/- 8.4 kg m-2], obese women with impaired glucose tolerance or overt non-insulin-dependent diabetes mellitus (NIDDM) (n = 10, BMI 49.1 +/- 11.6 kg m-2) and healthy non-obese control subjects (n = 12, BMI 25.8 +/- 2.7 kg m-2). RNA expression was assessed by a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique.
Results: The mean mRNA levels of both TNF receptors were two- to threefold higher in adipose tissue samples from the obese than from the non-obese women (P < 0.01 for each). Although TNFR60 mRNA did not vary within each obese group, there was a wide variation in the levels of TNFR80 mRNA and of TNF mRNA. A comparison of the expression levels between the subcutaneous abdominal and the omental adipose tissue depots showed significantly higher expression in the former. The TNFR60 expression level was positively correlated with BMI and fat cell size, whereas TNFR80 and TNF mRNA levels showed positive associations with serum insulin and triglyceride concentrations. No significant differences in the expression levels were observed between obese individuals with and without impaired glucose tolerance/NIDDM.
Conclusion: These results indicate that severe obesity in women is characterized by increased amounts of the two TNF receptor mRNAs. The role of this up-regulation for the development of obesity-associated insulin resistance remains to be elucidated.