THE EXPRESSION OF TUMOR-NECROSIS-FACTOR IN HUMAN ADIPOSE-TISSUE - REGULATION BY OBESITY, WEIGHT-LOSS, AND RELATIONSHIP TO LIPOPROTEIN-LIPASE

A previous study reported the increased expression of the cytokine TNF in the adipose tissue of genetically obese rodents, To examine this p aradigm in humans, we studied TNF expression in lean, obese, and reduc ed-obese human subjects, TNF mRNA was demonstrated in human adipocytes and adipose tissue by Northern blotting and PCR, TNF protein was quan titated by Western blotting and ELISA in both adipose tissue and the m edium surrounding adipose tissue, Using quantitative reverse transcrip tase PCR (RT-PCR), TNF mRNA levels were examined in the adipose tissue of 39 nondiabetic subjects, spanning a broad range of body mass index (BMI), There was a significant increase in adipose TNF mRNA levels wi th increasing adiposity, There was a significant correlation between T NF mRNA and percent body fat (r = 0.46, P < 0.05, n = 23), TNF mRNA te nded to decrease in very obese subjects, but when subjects with a BMI > 45 kg/m(2) were excluded, there was a significant correlation betwee n TNF mRNA and BMI(r = 0.37, P < 0.05, n = 32). In addition, there was a significant decrease in adipose TNF with weight loss, In 11 obese s ubjects who lost between 14 and 66 kg (mean 34.7 kg, or 26.6% of initi al weight), TNF mRNA levels decreased to 58% of initial levels after w eight loss (P < 0.005), and TNF protein decreased to 46% of initial le vels (P < 0.02), TNF is known to inhibit LPL activity. When fasting ad ipose LPL activity was measured in these subjects, there was a signifi cant inverse relationship between TNF expression and LPL activity (r = -0.39, P < 0.02, n = 39),With weight loss, LPL activity increased to 411% of initial levels, However, the magnitude of the increase in LPL did not correlate with the decrease in TNF, Thus, TNF is expressed in human adipocytes, TNF is elevated in most obese subjects and is decrea sed by weight loss, In addition, there is an inverse relationship betw een TNF and LPL expression, These data suggest that endogenous TNF exp ression in adipose tissue may help limit obesity in some subjects, per haps by increasing insulin resistance and decreasing LPL.