INHIBITION OF LIPOLYSIS IN ADIPOSE TISSUE BY METHYLISOXAZOLCARBOXYLIC ACIDS

5-Methylisoxazole-3-carboxylic acid (5-MICA) and 3-methylisoxazole-5-carboxylic acid (3-MICA) are strong inhibitors of fatty acid mobilization, 5-MICA being somewhat more potent than 3-MICA. Low doses of 5-MICA (20 μg/kg s.c.) depress plasma levels of unesterified fatty acids (UFA) in rats and small concentrations (10-7 m) reduce lipolysis in adipose tissue of fasting rats in vitro. 5-MICA acts on triglyceride hydrolysis, because it affects the release of UFA and glycerol to an equal extent. The antilipolytic effect is not associated with an increased reesterification, as the 14C-incorporation from glucose-U-14C into triglyceride-glycerol is reduced. Other pathways of glucose metabolism, however, such as oxidation to CO2 and fatty acid synthesis are stimulated. The incorporation of palmitate-1-14C into esterified fatty acids of isolated adipose tissue is also enhanced. Concentrations of 8·10-7 m 5-MICA totally prevent the lipolytic effects of caffeine and theophylline. On the other hand the lipolytic action of norepinephrine is only depressed to 70% by 8·10-5 m 5-MICA. The stronger inhibitory effect of 5-MICA on the lipolytic response evoked by a blockade of the phosphodiesterase suggests, that the antilipolytic action of 5-MICA could depend on an activation of the 3′,5′-AMP-phosphodiesterase. © 1968 Springer-Verlag.