Department of Epidemiology, School of Public Health, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Am J Clin Nutr. 2011 Feb;93(2):463-73. doi: 10.3945/ajcn.110.002949. Epub 2010 Dec 15.
Dietary magnesium intake has been favorably associated with reduced risk of metabolic outcomes in observational studies; however, few randomized trials have introduced a systems-biology approach to explore molecular mechanisms of pleiotropic metabolic actions of magnesium supplementation.
We examined the effects of oral magnesium supplementation on metabolic biomarkers and global genomic and proteomic profiling in overweight individuals.
We undertook this randomized, crossover, pilot trial in 14 healthy, overweight volunteers [body mass index (in kg/m(2)) ≥25] who were randomly assigned to receive magnesium citrate (500 mg elemental Mg/d) or a placebo for 4 wk with a 1-mo washout period. Fasting blood and urine specimens were collected according to standardized protocols. Biochemical assays were conducted on blood specimens. RNA was extracted and subsequently hybridized with the Human Gene ST 1.0 array (Affymetrix, Santa Clara, CA). Urine proteomic profiling was analyzed with the CM10 ProteinChip array (Bio-Rad Laboratories, Hercules, CA).
We observed that magnesium treatment significantly decreased fasting C-peptide concentrations (change: -0.4 ng/mL after magnesium treatment compared with +0.05 ng/mL after placebo treatment; P = 0.004) and appeared to decrease fasting insulin concentrations (change: -2.2 μU/mL after magnesium treatment compared with 0.0 μU/mL after placebo treatment; P = 0.25). No consistent patterns were observed across inflammatory biomarkers. Gene expression profiling revealed up-regulation of 24 genes and down-regulation of 36 genes including genes related to metabolic and inflammatory pathways such as C1q and tumor necrosis factor-related protein 9 (C1QTNF9) and pro-platelet basic protein (PPBP). Urine proteomic profiling showed significant differences in the expression amounts of several peptides and proteins after treatment.
Magnesium supplementation for 4 wk in overweight individuals led to distinct changes in gene expression and proteomic profiling consistent with favorable effects on several metabolic pathways. This trial was registered at clinicaltrials.gov as NCT00737815.
膳食镁摄入量与代谢结果风险降低呈正相关，这在观察性研究中已有报道；然而，很少有随机试验采用系统生物学方法来探索镁补充剂的多种代谢作用的分子机制。
我们研究了口服镁补充对超重个体代谢生物标志物及全基因组和蛋白质组谱的影响。
我们在 14 名健康、超重的志愿者（体重指数[BMI（kg/m2）]≥25）中进行了这项随机、交叉、先导试验，他们被随机分配接受柠檬酸镁（500 mg 元素镁/天）或安慰剂治疗 4 周，然后有 1 个月的洗脱期。根据标准化方案采集空腹血和尿标本。对血标本进行生化检测。提取 RNA，随后与 Human Gene ST 1.0 阵列（Affymetrix，Santa Clara，CA）杂交。用 CM10 ProteinChip 阵列（Bio-Rad Laboratories，Hercules，CA）分析尿蛋白质组谱。
我们发现，镁治疗显著降低了空腹 C 肽浓度（变化：镁治疗后-0.4ng/ml，安慰剂治疗后+0.05ng/ml；P=0.004），且似乎降低了空腹胰岛素浓度（变化：镁治疗后-2.2μU/ml，安慰剂治疗后 0.0μU/ml；P=0.25）。在炎症生物标志物中没有观察到一致的模式。基因表达谱分析显示，24 个基因上调，36 个基因下调，包括与代谢和炎症途径相关的基因，如 C1q 和肿瘤坏死因子相关蛋白 9（C1QTNF9）和血小板碱性蛋白前体（PPBP）。治疗后尿液蛋白质组谱显示几个肽和蛋白质的表达量有显著差异。
超重个体补充镁 4 周可导致基因表达和蛋白质组谱的明显改变，这与对多种代谢途径的有利影响一致。这项试验在 clinicaltrials.gov 注册，编号为 NCT00737815。
