Bezafibrate mildly stimulates ketogenesis and fatty acid metabolism in hypertriglyceridemic subjects.
Our objective was to determine whether bezafibrate, a hypotriglyceridemic drug and peroxisome proliferator-activated receptor (PPAR)-alpha agonist, is ketogenic and increases fatty acid oxidation in humans. We measured fatty acid metabolism and ketone levels in 13 mildly hypertriglycemic adults (67 +/- 11 years old) during 2 metabolic study days lasting 6 h, 1 day before and 1 day after bezafibrate (400 mg of bezafibrate per day for 12 weeks). beta-Hydroxybutyrate, triglycerides, free fatty acids, fatty acid profiles, insulin, and glucose were measured in plasma, and fatty acid beta-oxidation was measured in breath after an oral 50-mg dose of the fatty acid tracer [U-(13)C]linoleic acid. As expected, 12 weeks on bezafibrate decreased plasma triglycerides by 35%. Bezafibrate tended to raise postprandial beta-hydroxybutyrate, an effect that was significant after normalization to the fasting baseline values (p = 0.03). beta-Oxidation of [U-(13)C]linoleic acid increased by 30% (p = 0.03) after treatment. On the metabolic study day after bezafibrate treatment, postprandial insulin decreased by 26% (p = 0.01), and glucose concentrations were lower 2 to 5 h postprandially. Thus, in hypertriglyceridemic individuals, bezafibrate is mildly ketogenic and significantly changes fatty acid metabolism, effects that may be linked to PPARalpha stimulation and to moderately improved glucose metabolism.
Tremblay-Mercier
Jennifer
J
Research Center on Aging, University Institute of Geriatrics of Sherbrooke, Sherbrooke, Quebec, Canada. jennifer.tremblay-mercier@usherbrooke.ca
Tessier
Daniel
D
Plourde
Mélanie
M
Fortier
Mélanie
M
Lorrain
Dominique
D
Cunnane
Stephen C
SC
D000368:Aged; D001629:Bezafibrate / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001944:Breath Tests; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000097:blood
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007328:Insulin; D007657:Ketone Bodies; D014280:Triglycerides; D001629:Bezafibrate