Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance.
Previous studies have shown that tumor necrosis factor (TNF)-alpha production from adipose tissue is elevated in rodent and human obesity and plays an important role in insulin resistance in experimental animal models. In this study, we examined the adipose expression of both TNF receptors (TNFR1 and TNFR2) in human obesity and demonstrated that obese female subjects express approximately twofold more TNFR2 mRNA in fat tissue and approximately sixfold more soluble TNFR2 in circulation relative to lean control subjects. In contrast, TNFR1 expression and protein levels were similar in these subjects. TNFR2 expression levels in adipose tissue were strongly correlated with BMI (r = 0.65, P < 0.001) and level of hyperinsulinemia (P < 0.001), an indirect measure of insulin resistance, as well as level of TNF-alpha mRNA expression in fat tissue (r = 0.56, P < 0.001). These results suggest that TNFR2 might play a role in human obesity by modulating the actions of TNF-alpha.
Hotamisligil
G S
GS
Department of Nutrition, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA. ghotamis@hsph.harvard.edu
Arner
P
P
Atkinson
R L
RL
Spiegelman
B M
BM
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis*; D015152:Blotting, Northern; D015992:Body Mass Index; D001835:Body Weight; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007333:Insulin Resistance; D009765:Obesity / Q000378:metabolism*; D017697:Premenopause; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D012044:Regression Analysis
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II