Clausen Morten Rahr, Zhang Xumin, Yde Christian C, Ditlev Ditte B, Lillefosse Haldis H, Madsen Lise, Kristiansen Karsten, Liaset Bjørn, Bertram Hanne C
Department of Food Science, Aarhus University, Aarslev, Denmark.
Department of Food Science, Aarhus University, Aarslev, Denmark; State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.
PLoS One. 2015 Mar 4;10(3):e0118895. doi: 10.1371/journal.pone.0118895. eCollection 2015.
The amount and form of dietary casein have been shown to affect energy metabolism and lipid accumulation in mice, but the underlying mechanisms are not fully understood. We investigated 48 hrs urinary metabolome, hepatic lipid composition and gene expression in male C57BL/6J mice fed Western diets with 16 or 32 energy% protein in the form of extensively hydrolyzed or intact casein. LC-MS based metabolomics revealed a very strong impact of casein form on the urinary metabolome. Evaluation of the discriminatory metabolites using tandem mass spectrometry indicated that intake of extensively hydrolyzed casein modulated Phase II metabolism associated with an elevated urinary excretion of glucuronic acid- and sulphate conjugated molecules, whereas glycine conjugated molecules were more abundant in urine from mice fed the intact casein diets. Despite the differences in the urinary metabolome, we observed no differences in hepatic expression of genes involved in Phase II metabolism, but it was observed that expression of Abcc3 encoding ATP binding cassette c3 (transporter of glucuronic acid conjugates) was increased in livers of mice fed hydrolyzed casein. As glucuronic acid is derived from glucose and sulphate is derived from cysteine, our metabolomic data provided evidence for changes in carbohydrate and amino acid metabolism and we propose that this modulation of metabolism was associated with the reduced glucose and lipid levels observed in mice fed the extensively hydrolyzed casein diets.
膳食酪蛋白的量和形式已被证明会影响小鼠的能量代谢和脂质积累，但其潜在机制尚未完全了解。我们研究了以广泛水解或完整酪蛋白形式提供16%或32%能量蛋白质的西方饮食喂养的雄性C57BL/6J小鼠的48小时尿液代谢组、肝脏脂质组成和基因表达。基于液相色谱-质谱联用的代谢组学研究表明，酪蛋白形式对尿液代谢组有非常强烈的影响。使用串联质谱对具有鉴别性的代谢物进行评估表明，摄入广泛水解的酪蛋白会调节II期代谢，这与葡萄糖醛酸和硫酸盐结合分子的尿排泄增加有关，而在喂食完整酪蛋白饮食的小鼠尿液中，甘氨酸结合分子更为丰富。尽管尿液代谢组存在差异，但我们未观察到参与II期代谢的基因在肝脏中的表达有差异，但观察到在喂食水解酪蛋白的小鼠肝脏中，编码ATP结合盒c3（葡萄糖醛酸结合物转运蛋白）的Abcc3表达增加。由于葡萄糖醛酸来自葡萄糖，硫酸盐来自半胱氨酸，我们的代谢组学数据为碳水化合物和氨基酸代谢的变化提供了证据，并且我们提出这种代谢调节与喂食广泛水解酪蛋白饮食的小鼠中观察到的葡萄糖和脂质水平降低有关。
