Research Center on Aging, University Institute of Geriatrics of Sherbrooke, Sherbrooke, Quebec, Canada.
J Pharmacol Exp Ther. 2010 Jul;334(1):341-6. doi: 10.1124/jpet.110.166504. Epub 2010 Apr 19.
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.
我们的目的是确定贝特类降脂药（一种降低甘油三酯的药物和过氧化物酶体增殖物激活受体（PPAR）-α激动剂）是否具有生酮作用，并能增加人体的脂肪酸氧化。我们在 13 名轻度高甘油三酯血症成年人（67±11 岁）中进行了 2 天的代谢研究，每次 6 小时，在服用贝特类药物（每天 400mg，持续 12 周）前 1 天和后 1 天各进行 1 次。我们在血浆中测量了β-羟丁酸、甘油三酯、游离脂肪酸、脂肪酸谱、胰岛素和葡萄糖，在口服 50mg[U-(13)C]亚油酸示踪剂后测量了脂肪酸β氧化。正如预期的那样，服用贝特类药物 12 周后，血浆甘油三酯降低了 35%。贝特类药物使餐后β-羟丁酸水平升高，这种作用在正常化到空腹基线值后变得显著（p=0.03）。治疗后[U-(13)C]亚油酸的β氧化增加了 30%（p=0.03）。在服用贝特类药物后的代谢研究日，餐后胰岛素降低了 26%（p=0.01），并且餐后 2-5 小时血糖浓度较低。因此，在高甘油三酯血症患者中，贝特类药物具有轻度生酮作用，并显著改变脂肪酸代谢，这些作用可能与 PPARα 刺激和适度改善的葡萄糖代谢有关。
