The effect of etomoxir on 24-h substrate oxidation and satiety in humans.
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.


METHODS
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/m(2)): 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.
Hinderling
Vera B
VB
Institute of Animal Sciences, Swiss Federal Institute of Technology, Zürich, Switzerland. vhi@rdia.azm.nl
Schrauwen
Patrick
P
Langhans
Wolfgang
W
Westerterp-Plantenga
Margriet S
MS
D020155:3-Hydroxybutyric Acid / Q000097:blood; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002334:Carnitine O-Palmitoyltransferase / Q000037:antagonists & inhibitors; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D006801:Humans; D006815:Hunger; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010084:Oxidation-Reduction; D010919:Placebos; D012527:Satiation / Q000187:drug effects*; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D004791:Enzyme Inhibitors; D004852:Epoxy Compounds; D005227:Fatty Acids; D010919:Placebos; D014280:Triglycerides; D019344:Lactic Acid; D002334:Carnitine O-Palmitoyltransferase; C054207:etomoxir; D005990:Glycerol; D020155:3-Hydroxybutyric Acid