Metabolic Research Centre, School of Medicine and Pharmacology, The University of Western Australia, Nedlands, Australia.
Diabetes Obes Metab. 2014 Jun;16(6):519-26. doi: 10.1111/dom.12243. Epub 2013 Dec 29.
To test the effect of atorvastatin (ATV) and ATV plus ω-3 FAEEs on VLDL-TG metabolism in obese, insulin resistant men.
We carried out a 6-week randomized, placebo-controlled study to examine the effect of ATV (40 mg/day) and ATV plus ω-3 FAEEs (4 g/day) on VLDL-TG metabolism in 36 insulin resistant obese men. VLDL-TG kinetics were determined using d5 -glycerol, gas chromatography-mass spectrometry and compartmental modelling.
Compared with the placebo, ATV significantly decreased VLDL-TG concentration (-40%, p < 0.001) by increasing VLDL-TG fractional catabolic rate (FCR) (+47%, p < 0.01). ATV plus ω-3 FAEEs lowered VLDL-TG concentration to a greater degree compared with placebo (-46%, p < 0.001) or ATV monotherapy (-13%, p = 0.04). This was achieved by a reduction in VLDL-TG production rate (PR) compared with placebo (-32%, p = 0.008) or ATV (-20%, p = 0.03) as well as a reciprocal increase in VLDL-TG FCR (+42%, p < 0.05) compared with placebo.
In insulin resistant, dyslipidaemic, obese men, ATV improves VLDL-TG metabolism by increasing VLDL-TG FCR. The addition of 4 g/day ω-3 FAEE to statin therapy provides further TG-lowering by lowering VLDL-TG PR.
研究阿托伐他汀(ATV)和 ATV 联合 ω-3 脂肪酸乙酯(ω-3 FAEEs)对肥胖、胰岛素抵抗男性患者极低密度脂蛋白甘油三酯(VLDL-TG)代谢的影响。
我们进行了一项为期 6 周的随机、安慰剂对照研究,以观察 ATV(40mg/天)和 ATV 联合 ω-3 FAEEs(4g/天)对 36 名胰岛素抵抗肥胖男性患者 VLDL-TG 代谢的影响。使用 d5 -甘油、气相色谱-质谱联用和房室模型分析来测定 VLDL-TG 动力学。
与安慰剂相比,ATV 显著增加了 VLDL-TG 分解代谢率(FCR)(+47%,p<0.01),从而降低了 VLDL-TG 浓度(-40%,p<0.001)。与安慰剂(-46%,p<0.001)或 ATV 单药治疗(-13%,p=0.04)相比,ATV 联合 ω-3 FAEEs 降低 VLDL-TG 浓度的程度更大。这是通过降低 VLDL-TG 生成率(PR)实现的,与安慰剂(-32%,p=0.008)或 ATV(-20%,p=0.03)相比,以及 VLDL-TG FCR 的反方向增加(+42%,p<0.05)与安慰剂相比。
在胰岛素抵抗、血脂异常的肥胖男性中,ATV 通过增加 VLDL-TG FCR 来改善 VLDL-TG 代谢。在他汀类药物治疗的基础上加用 4g/天 ω-3 FAEEs 可通过降低 VLDL-TG PR 进一步降低 TG。