Lipolysis and adenosine 3':5'-monophosphate metabolism in isolated white fat cells from genetically obese hyperglycemic mice (ob/ob)

Lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation were measured in isolated fat cells prepared from obese hyperglycemic mice (ob/ob) and lean littermates at 5 months of age. Fat cells from the ob/ob mice displayed near normal lipolysis even though the maximal cyclic AMP levels of these fat cells were significantly lower than the fat cells from lean littermates. Basal triglyceride lipase activity and activation by cyclic AMP were similar in the ob/ob and the lean mice. Adenylate cyclase in ghosts prepared from ob/ob mice fat cells was minimally responsive to norepinephrine. However, ghosts prepared from fat cells of lean or ob/ob mice were equally responsive to fluoride or 10 μM guanyl-5'-yl imidodiphosphate. Norepinephrine stimulation of adenylate cyclase was not potentiated by guanyl-5'-yl imidodiphosphate in fat cell ghosts from ob/ob mice. Total cyclic AMP phosphodiesterase activity measured at 0.125 and 1.025 μM cyclic AMP was more than 50% higher per cell in the fat cells obtained from ob/ob mice as compared to their lean littermates. Most (80%) of the homogenate cyclic AMP phosphodiesterase activity was in the supernatant fraction. The specific activity was similar in the supernatant fraction from fat cells of lean as compared to ob/ob mice. However, the specific activity of the particulate cyclic AMP phosphodiesterase was markedly reduced in ob/ob mice. The sensitivity of the particulate cyclic AMP phosphodiesterase to methyl xanthines was unaffected by obesity while that of the soluble fraction from ob/ob mice was reduced. These data indicate that although cyclic AMP accumulation by isolated fat cells in response to norepinephrine is markedly lower in ob/ob animals, lipolysis and triglyceride lipase activation were essentially unaltered.