Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs

Abstract

Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1- 14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 ± 25 to 47 ± 6 μmol/L and 2.9 ± 0.5 to 0.9 ± 0.2 μmol·kg −1·min −1, respectively, at 15 minutes, both P < .05). Palmitate oxidation also decreased, from 1.5 ± 0.4 to 0.3 ± 0.1 μmol·kg −1·min −1, P < .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration ( P < .05). Fractional oxidation of palmitate also decreased by approximately 40% ( P < .05). Plasma insulin increased from 45 ± 6 to 240 ± 93 pmol/L at 15 minutes ( P < .05). Plasma glucose decreased over the course of study by approximately 20% ( P < .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.