Summary
This study was designed to examine the time-course of response to inhibition of fatty
acid (FA) oxidation in rats rendered mildly diabetic with streptozotocin and fed a
high fat diet (50% of energy derived from fat). Etomoxir, a specific carnitine palmitoyltransferase
(CPT-1) inhibitor, was administered subcutaneously (12.5 mg/kg) to inhibit long chain
fatty acid oxidation. Diabetic and non-diabetic control rats were maintained on the
high fat diet. Following an overnight fast, glucose, free fatty acid (FFA) and triglyceride
(TG) concentrations were determined after three days, one week and four weeks of treatment.
The effect of Etomoxir treatment in reducing fasting glucose concentrations was not
evident until after one week, while fasting FFA and TG concentrations were already
reduced after three days treatment. All of these changes were maintained over the
four week period (P < 0.001), resulting in reduced levels of fasting plasma glucose
(17.6±2.4 vs 22.3±1.9 mmol/l), fasting plasma TG (0.32±0.07 vs 0.98±0.14 mmol/l) and
fasting serum FFA (1.52±0.26 vs 3.51±0.69 mEq/l). In addition, the improvements in
glucose and lipid levels were accompanied by restored rates of growth towards that
of non-diabetic control rats. These results suggest that the short term inhibition
of FA oxidation improves fasting glucose, FFA and TG concentrations in diabetic rats
fed a high fat diet.
Key words
Fatty Acid Oxidation - Etomoxir - Diabetes - Rats - Streptozotocin - High Fat Diet
