EXPRESSION OF NERVE GROWTH-FACTOR IN BROWN ADIPOSE-TISSUE - IMPLICATIONS FOR THERMOGENESIS AND OBESITY

The presence of nerve growth factor (NGF) and the ability of adrenergi c stimulation to affect the rate of its synthesis in mouse, rat, and h uman brown adipose tissue (BAT) were investigated. Addition of conditi oned medium, obtained from preconfluent and confluent brown adipocytes , to PC12 cells induced typical morphological changes similar to those due to NGF itself. Anti-NGF antibodies blocked this action. Moreover, NGF mRNA was detected by RT-PCR both in BAT and in brown adipocyte pr eparations: That NGF is synthesized in and released from brown fat cel ls was confirmed by immunoblotting. When the animals were exposed to l ow temperatures, NGF production declined. The effect of cold exposure could be mimicked by the addition of norepinephrine (NE) at day 4 or 8 (preconfluent and confluent cells, respectively). NE depletion obtain ed by reserpine injection induced a drastic increase of BAT NGF produc tion. In both rat and human BAT, immunohistochemistry identified disti nct anatomical structures that express the low affinity neurotropin re ceptor, termed p75(NGFR). BAT production of NGF was higher in genetica lly obese rats and mice than in their lean counterparts, a difference that becomes more evident with age. Prolonged exposure to low temperat ure significantly decreased the BAT NGF synthesis also in obese animal s. We conclude that NGF is synthesized in and released from brown fat cells, its production being inversely dependent on sympathetic activit y, in both physiological and pathophysiological conditions, and increa sed in genetic animal models of obesity.