Cardiovasc Res. 2011 May 28.
Aims 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 remain incompletely understood. Thus, we investigated whether a combination of micronutrients would reduce fat accumulation and atherosclerosis in mice. Methods and Results 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 reduced lipid accumulation in metabolic organs and 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 triglyceridemia and vascular inflammation, two major atherogenic factors. Conclusions Our data indicate beneficial effects of a combination of micronutritients on body weight gain, hypertriglyceridemia, liver steatosis, and atherosclerosis in mice and thus, our findings suggest a novel cost-effective combinatorial micronutrient-based strategy worth to be tested in humans.