Abstract
Forskolin (7 beta-acetoxy-8, 13-epoxy-1 alpha,6 beta,9 alpha-trihydroxy-labd-14-ene-11-one) induced both cyclic AMP production and lipolysis in intact fat cells, but stimulated lipolysis without increasing cyclic AMP at a concentration of 10(-5) M. Homogenization of fat cells elicited lipolysis without elevation of cyclic AMP. Forskolin did not stimulate lipolysis in the homogenate. Forskolin stimulated both cyclic AMP production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. However, at a concentration of 10(-6) M, it induced lipolysis without increase in the cyclic AMP content in this cell-free system. In the cell-free system, homogenization of the lipid droplets resulted in marked increase in lipolysis to almost the same level as that with 10(-4) M forskolin without concomitant increase in cyclic AMP. Addition of forskolin to a cell-free system consisting of homogenized lipid droplets and lipase did not stimulate lipolysis further. Phosphodiesterase activities were found to be almost the same both in the presence and absence of forskolin in these reaction mixtures. Although 10(-3) M forskolin produced maximal concentrations of cyclic AMP: 6.7 x 10(-7) M in fat cells and 2.7 x 10(-7) M in the cell-free system, 10(-4) M cyclic AMP did not stimulate lipolysis in the cell-free system. In a cell-free system consisting of lipid droplets and the lipase, pyrophosphate inhibited forskolin-induced cyclic AMP production, but decreased forskolin-mediated lipolysis only slightly. Based on these results, mechanism of lipolytic action of forskolin was discussed.
Highlights
Mooney, Swicegood, and Marx [2]reported that increase in adenylate cyclase activity above a basal level the homogenate
Homogenization of fat cells resulted in lipolysis in the absence of forskolin, which was not affected by the addition of forskolin (Fig. 1)
We examined the effects of forskolin on lipolysis and cyclic AMP production in fat cells and a cell-free system consisting of endogenous lipid droplets from fat cells and lipase containing hormone-sensitive lipase
Summary
Swicegood, and Marx [2]reported that increase in adenylate cyclase activity above a basal level the homogenate Forskolin stimulated both cyclic AMP required to activate lipolysis in response to forskolin production and lipolysis in a cell-free system consisting of endogenous lipid droplets and a lipoprotein lipase-free lipase fraction prepared from fat cells. In the cellwas 5 times that with isoproterenol in both intact and permeabilized fat cells They suggested that these results could be due to activation of lipolysis mediated by a kadrenergic agent and its receptor independently free system, homogenization of the lipid droplets resulted in of cyclic AMP. In a cell-free system consisting of lipid droplets and stimulated lipolysis of endogenous lipid droplets from fat cells by lipase solution In this system, these lipolytic agents did not induce lipolysis in the absence of added lipase.
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Published Version
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