Changes in thermogenesis and brown fat activity in response to tumour necrosis factor in the rat

A single intravenous injection of recombinant human tumour necrosis factor (TNF) resulted in significant, but transient (24-48 hr) reductions in food intake and body weight, and increases in rectal temperature, resting oxygen consumption (VO2) and brown adipose tissue (BAT) thermogenic activity (mitochondrial GDP-binding). The increased VO2 was inhibited by beta-adrenergic blockade (propranolol), and activation of BAT was prevented by denervation of the tissue. In adult (4-month old) animals, TNF induced greater reductions in food intake and body weight, caused general malaise and some fatalities, but did not significantly alter VO2 or BAT activity. However, the reduction in VO2 following beta-adrenergic blockade was greater in TNF-treated rats and BAT activity was enhanced when compared to pair-fed controls. Injection of adult rats with gamma-interferon induced small changes in body weight and temperature which were slightly potentiated when injected with a low dose of TNF. The results indicate that TNF stimulates sympathetic outflow to BAT. This effect may be partly responsible for the increases in body temperature and metabolic rate associated with TNF treatment and with cancer cachexia.