Expression pattern of tumour necrosis factor receptors in subcutaneous andomental human adipose tissue: role of obesity and non-insulin-dependent diabetes mellitus

Background Tumour necrosis factor alpha (TNF) mRNA expression has been repo rted to be up-regulated in adipose tissue from several rodent models of obe sity and diabetes and from obese humans. This elevated expression has been assumed to be associated with the development of insulin resistance. Howeve r, 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-d ependent 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)). R NA expression was assessed by a semiquantitative reverse transcriptase poly merase chain reaction (RT-PCR) technique. Results The mean mRNA levels of both TNF receptors were two- to threefold h igher in adipose tissue samples hom the obese than horn the non-obese women (P < 0.01 for each). Although TNFR60 mRNA did not vary within each obese g roup, there was a wide variation in the levels of TNFR80 mRNA and of TNF mR NA. A comparison of the expression levels between the subcutaneous abdomina l and the omental adipose tissue depots showed significantly higher express ion in the former. The TNFR60 expression level was positively correlated wi th BMI and fat cell size, whereas TNFR80 and TNF mRNA levels showed positiv e associations with serum insulin and triglyceride concentrations. No signi ficant differences in the expression levels were observed between obese ind ividuals with and without impaired glucose tolerance/NIDDM. Conclusion These results indicate that severe obesity in women is character ized by increased amounts of the two TNF receptor mRNAs. The role of this u p-regulation for the development of obesity-associated insulin resistance r emains to be elucidated.