Forskolin potentiates isoprenaline-induced glycerol output and local blood flow in human adipose tissue in vivo

The synergistic action of forskolin on beta-adrenoceptor-mediated glycerol output and changes in local blood flow were investigated in situ, in human adipose tissue of healthy subjects, by the use of microdialysis. The addition of isoprenaline 0.1-1.0 mu M or forskolin 10-100 mu M to the perfusion solvent caused a concentration-dependent, marked and sustained increase in the levels of glycerol in the dialysate (lipolysis index) as compared to the solvent alone. On a molar basis, isoprenaline was almost one thousand times more potent than forskolin. Isoprenaline caused a rapid and concentration-dependent decrease in the ethanol clearance ratio (index of local blood flow, i.e. a decrease in ethanol ratio implies an increase in blood flow). Forskolin had no effect on the ethanol ratio at either 1.0 mu M or 10 mu M, while forskolin at 100 mu M induced a significant decrease in the ethanol ratio. When adipose tissue was pre-treated with forskolin, the subsequent addition of isoprenaline to the microdialysate resulted in a significantly higher glycerol output and a significantly more prominent decease in the ethanol ratio than with isoprenaline alone. In conclusion, the data demonstrate that forskolin and the beta-adenoceptor-agonist both stimulate lipolysis and local blood flow in human adipose tissue in vivo. Furthermore, forskolin, at concentrations that are ineffective alone, potentiates the actions of isoprenaline on lipolysis and blood flow.