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American Journal of Clinical Nutrition, Vol. 76, No. 1, 141-147, July 2002
© 2002 American Society for Clinical Nutrition

Original Research Communication

The effect of etomoxir on 24-h substrate oxidation and satiety in humans1,2,3

Vera B Hinderling, Patrick Schrauwen, Wolfgang Langhans and Margriet S Westerterp-Plantenga

1 From the Institute of Animal Sciences, Swiss Federal Institute of Technology, Zürich, Switzerland (VBH and WL), and the Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), University of Maastricht, Maastricht, Netherlands (PS and MSW-P).

Background: The carnitine O-palmitoyltransferase I (EC 2.3.1.21) inhibitor etomoxir inhibits fatty acid oxidation, and hepatic fatty acid oxidation has been suggested to be a metabolic satiety signal in subjects who consume high-fat diets.

Objective: We investigated substrate oxidation and satiety after repeated administrations of etomoxir or placebo in subjects who consumed a high-fat diet.

Design: In a randomized crossover design consisting of three 5-d treatments, we fed 10 healthy men [mean ± SE age: 25.6 ± 1.7 y; mean ± SE body mass index (in kg/m2): 21.8 ± 0.3] a high-fat diet twice and a low-fat diet once. The subjects consumed each diet at home for 3 consecutive days, after which they spent 36 h in energy balance in a respiration chamber. During the chamber stays with the high-fat treatments, etomoxir or placebo was administered in 5 doses (600 mg etomoxir in total). Blood samples were obtained on the mornings of days 4 and 5 of each treatment, and appetite profiles were assessed.

Results: Mean (±SE) 24-h respiratory quotients were significantly (P < 0.05) higher with repeated administrations of etomoxir (0.833 ± 0.004) than with repeated administrations of placebo (0.814 ± 0.006), and mean (±SE) 24-h whole-body fat oxidation tended to be less (13.7%, P = 0.06) with administration of etomoxir (136.0 ± 5.2 g/d) than with administration of placebo (157.5 ± 5.6 g/d). With the etomoxir treatment, fat balance was positive (P < 0.0001) and carbohydrate balance was negative (P < 0.001), whereas with the placebo treatment, neither of the balances was significantly different from zero. Hunger and satiety ratings were not affected under these conditions.

Conclusions: Etomoxir decreased whole-body fat oxidation, as indicated by the respiratory quotients in the healthy subjects. With the current protocol, however, hunger and satiety ratings were not affected.

Key Words: Hepatic fatty acid oxidation • respiration chamber • macronutrient composition • obesity • etomoxir






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