Tumor necrosis factor-alpha induces apoptosis in rat brown adipocytes

Accumulating evidence demonstrates that adipose tissue is a major site of tumor necrosis factor-alpha (TNF-alpha) gene expression, which is markedly high in obese animals and may contribute to obesity-linked insulin resistance. We now report that recombinant murine TNF-alpha triggers the apoptotic degeneration of brown adipocytes differentiated in culture. Moreover, noradrenaline, which has been described as having trophic effects on brown fat and accelerating the differentiation of brown adipocytes, is capable of dose-dependently preventing the TNF-alpha-induced apoptosis of brown fat cells. Since obesity is characterized by greatly increased TNF-alpha production and reduced catecholaminergic activity, apoptosis was studied in the brown fat of genetically obese animals. In situ DNA fragmentation analysis revealed a larger number of apoptotic cells in the brown fat of obese (fa/fa) than in that of lean (+/+) Zucker rats. The exposure of obese rats to low temperatures for 7 days, which increases the sympathetic activity of brown adipose tissue, significantly reduces the number of apoptotic brown adipocytes. We hypothesize that TNF-alpha may play a significant role in the control of brown fat homeostasis.