TNFa release by the nonfat cells of human adipose tissue

OBJECTIVE: The primary aim was to investigate the relative importance of the adipocytes vs the nonfat cells present in human adipose tissue with respect to release of immunoreactive tumor necrosis factor-alpha (TNFalpha). The second aim was to examine the correlation between body mass index ( BMI) and the subsequent release of adiponectin and TNFalpha by explants of human subcutaneous and visceral adipose tissue incubated in primary culture for 48 h. RESULTS: We found that the maximal release of TNFalpha was seen during the first 4 h of a 48- h incubation by explants of human adipose tissue in primary culture. Over 95% of the TNFalpha released to the medium by human adipose tissue explants over a 4- h incubation came from the nonfat cells present in the adipose tissue. The release of TNFalpha by the nonfat cells released during collagenase digestion was slightly higher than that by the cells present in the adipose tissue matrix after collagenase digestion. TNFalpha release by the combined matrix and isolated nonfat cells was greater than that by explants of tissue indicating some upregulation induced by collagenase digestion. Immunoreactive TNFalpha disappeared from the medium with a half- time of approximately 10 h. There was a positive correlation coefficient of 0.79 between TNFalpha release by tissue explants and the BMI of the fat donors as well as a correlation of 0.52 between BMI and release by adipocytes. TNFalpha release negatively correlated [ - 0.60] with adiponectin release by adipose tissue. The release of TNFalpha was far less than that of adiponectin or IL- 6, and less than that of plasminogen activator inhibitor- 1, hepatocyte growth factor, or leptin over a 4- h incubation of human adipose tissue explants. TNFalpha release over 4 h was enhanced by lipopolysaccharide and inhibited by a cyclooxygenase- 2 inhibitor. CONCLUSION: The release of TNFalpha by adipose tissue of obese humans is primarily due to the nonfat cells present in adipose tissue. TNFalpha is a short- lived adipokine whose release by human adipose tissue in primary culture correlates with the BMI of the fat donors.