Inhibition of free fatty acid mobilization by colchicine

Segments of epididymal adipose tissue from normal male rats were incubated with micromolar concentrations of colchicine for different periods of time up to 4 hr, and the mobilization of free fatty acids (FFA) was measured during a subsequent reincubation. Although pretreatment with colchicine did not alter basal unstimulated FFA release, mobilization of FFA in the presence of epinephrine or theophylline was reduced. However, neither lipolysis, as judged by glycerol production, nor cyclic AMP accumulation was impaired under the same conditions. To assess the possibility that colchicine might limit production of fatty acids by accelerating the entry and metabolism of glucose into adipocytes, the metabolism of glucose by adipose tissue was studied. Pretreatment with colchicine did not affect uptake of glucose nor its oxidation to C o n , although colchicinetreated tissues did have slightly more [ *C]glucose incorporated into the glyceride moiety of triglyceride. -When adipose tissues pretreated with colchicine were incubated in an albumin-free medium, no reduction in FFA production by colchicine was observed. Because no FFA release occurs in albumin-free media, this experiment suggests that colchicine-induced inhibition of FFA mobilization results from impaired extrusion of FFA from adipose cells. Supplementary key words sue . microtubules lipolysis . glucose oxidation . adipose tisIn adipose tissue, triglycerides are constantly being hydrolyzed to free fatty acids (FFA) and glycerol and reformed from FFA and a-glycerophosphate. Although the cellular mechanisms underlying the hydrolysis and resynthesis of triglycerides are well understood (l), the mechanisms by which FFA are released from adipocytes into the circulation remain obscure. It has been tacitly assumed that the egress of FFA from adipose tissue occurs by passive diffusion consequent to their formation and accumulation within adipocytes (2). This view has been called into question, however, by recent experiments suggesting that the extrusion of FFA from segments of adipose tissue (3) and from isolated adipocytes (4) requires the expenditure of energy. The studies reported herein indicate that the mobilization of FFA from adipose tissue is susceptible to inhibition by micromolar concentrations of the antimitotic drug colchicine. In view of the well-documented action of colchicine blocking numerous secretory processes (5-7), it is suggested that colchicine inhibits the extrusion of FFA