Development and activation of brown fat in rats with pheochromocytoma PC 12 tumors

D. Ricquier, G. Mory, M. Nechad, M. Combes-George and J. Thibault To study the neurohormonal determinism of cellular growth and differentiation and mitochondrial development in brown adipose tissue (BAT), this organ was analyzed in rats bearing uncloned or cloned (PC 12) pheochromocytoma; comparison was made with cold adaptation. Both uncloned and PC 12 tumors induced an enlargement of tissue weight and DNA total content, although smaller than during cold adaptation. The following striking modifications were observed in rats bearing PC 12 tumors: strong vasodilation, increase in protein and phospholipid percentage, alteration of the fatty acid composition of phospholipids, increase in mitochondrial protein, large increase of the GDP binding to isolated mitochondria, and marked rise in specific amount of 32,000-dalton uncoupling protein (ascertained using immunological approach). It is concluded that secretions of PC 12 tumors can induce the same alterations in BAT as does the sympathetic system during cold adaptation of animals. An important contribution of norepinephrine to these effects is evidenced, but a specific function of other trophic factors secreted by PC 12 cells and by sympathetic nerves can be postulated.