Abstract
Our objective was to determine whether bezafibrate, a hypotriglyceridemic drug and peroxisome proliferator-activated receptor (PPAR)-α 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). β-Hydroxybutyrate, triglycerides, free fatty acids, fatty acid profiles, insulin, and glucose were measured in plasma, and fatty acid β-oxidation was measured in breath after an oral 50-mg dose of the fatty acid tracer [U-13C]linoleic acid. As expected, 12 weeks on bezafibrate decreased plasma triglycerides by 35%. Bezafibrate tended to raise postprandial β-hydroxybutyrate, an effect that was significant after normalization to the fasting baseline values (p = 0.03). β-Oxidation of [U-13C]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 PPARα stimulation and to moderately improved glucose metabolism.
Footnotes
This work was supported by Research Center on Aging, Natural Sciences and Engineering Research Council of Canada [Grant 3606-2008] and Canada Research Chair [Grant 950-201796].
This work is based on the following work: Tremblay-Mercier J (2009) Étude des fibrates en tant qu'agent stimulateurs de la synthèse des cétones, des substrats énergétiques pour le cerveau vieillissant, Master's thesis, the Medecine and Health Science Faculty of Université de Sherbrooke, Sherbrooke, QC, Canada.
Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.110.166504.
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ABBREVIATIONS:
- AD
- Alzheimer's disease
- β-OHB
- β-hydroxybutyrate
- MCT
- medium-chain triglyceride(s)
- PPAR
- peroxisome proliferator-activated receptor
- TG
- triglyceride(s)
- AST
- aspartate aminotransferase
- ALT
- alanine aminotransferase
- HOMA-IR
- homeostasis model assessment-insulin resistance
- HDL
- high-density lipoprotein
- LDL
- low-density lipoprotein
- FFA
- free fatty acid(s)
- AUC
- area under the curve.
- Received February 3, 2010.
- Accepted April 16, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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