Relation of fat cell ATP content to lipolysis induced by dibutyryl 3′,5′, cyclic AMP

Abstract

To assess the relationship between adipocyte ATP content and the activation of hormone sensitive lipase by cyclic AMP, fat cell ATP values were manipulated by incubation of cells with varying concentrations of either oligomycin or 2-deoxy-D-glucose after which the cells were exposed to dibutyryl 3′,5′, cyclic AMP. While reductions in fat cell ATP content induced by either agent were associated with reductions in subsequent lipolysis, the effect of ATP depletion varied with the agent and with the concentration of dibutyryl cyclic AMP used. At low concentrations of dibutyryl cyclic AMP (0.75 × 10 −3 M), when oligomycin and 2-deoxy-D-glucose induced similar marked reductions in ATP, they were equally effective in reducing lipolysis. At low ATP levels, increases in concentration of dibutyryl cyclic AMP induced increments in lipolytic response and these increments were much greater in cells treated with 2-deoxy-D-glucose than with oligomycin. At all ATP levels, the lipolytic response to 3.0 × 10 −3 M dibutyryl cyclic AMP was greater in 2-deoxy-D-glucose than in oligomycin treated cells. Despite these differences, the effects of oligomycin and 2-deoxy-D-glucose on lipolysis were probably mediated through a common mechanism since the inhibition of lipolysis produced by combinations of the two agents was less than the sum of the individual inhibitory effects. These results indicate that the activation of hormone sensitive lipase induced by cyclic AMP requires ATP. It is suggested that the ATP involved in the activation process is less affected by processes that reduce total ATP content by hexose phosphorylation than by those that inhibit oxidative phosphorylation. It is also suggested that the concentration of cyclic AMP determines not only the requirement of the lipase activation process for ATP but also the affinity of ATP for a component of this process.