Center for Integrative Genomics, National Research Center Frontiers in Genetics, University of Lausanne, CH 1015 Lausanne, Switzerland.
Cardiovasc Res. 2011 Sep 1;91(4):732-41. doi: 10.1093/cvr/cvr146. Epub 2011 May 28.
More than two billion people worldwide are deficient in key micronutrients. Single micronutrients have been used at high doses to prevent and treat dietary insufficiencies. Yet the impact of combinations of micronutrients in small doses aiming to improve lipid disorders and the corresponding metabolic pathways remains incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice.
Lipoprotein receptor-null mice fed with an original combination of micronutrients incorporated into the daily chow showed reduced weight gain, body fat, plasma triglycerides, and increased oxygen consumption. These effects were achieved through enhanced lipid utilization and reduced lipid accumulation in metabolic organs and were mediated, in part, by the nuclear receptor PPARα. Moreover, the micronutrients partially prevented atherogenesis when administered early in life to apolipoprotein E-null mice. When the micronutrient treatment was started before conception, the anti-atherosclerotic effect was stronger in the progeny. This finding correlated with decreased post-prandial triglyceridaemia and vascular inflammation, two major atherogenic factors.
Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridaemia, liver steatosis, and atherosclerosis in mice, and thus our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worthy of being tested in humans.
全球有超过 20 亿人缺乏关键微量营养素。曾使用高剂量的单一微量营养素来预防和治疗饮食不足。然而，小剂量组合微量营养素对改善脂质紊乱及相应代谢途径的影响仍不完全清楚。因此，我们研究了组合微量营养素是否会减少小鼠的脂肪积累和动脉粥样硬化。
给予饮食中纳入了原始组合微量营养素的脂蛋白受体缺失小鼠，体重增加、体脂肪、血浆甘油三酯减少，耗氧量增加。这些作用是通过增强脂质利用和减少代谢器官中的脂质积累来实现的，部分是通过核受体 PPARα 介导的。此外，当在生命早期给予载脂蛋白 E 缺失小鼠时，这些微量营养素部分预防了动脉粥样硬化的发生。当在受孕前开始微量营养素治疗时，后代的抗动脉粥样硬化作用更强。这一发现与餐后甘油三酯血症和血管炎症的减少有关，这是两个主要的动脉粥样硬化因素。
我们的数据表明，组合微量营养素对小鼠体重增加、高甘油三酯血症、肝脂肪变性和动脉粥样硬化有有益的影响，因此我们的研究结果表明，一种新的具有成本效益的组合微量营养素为基础的策略值得在人类中进行测试。
