Díaz-Rúa Rubén, Keijer Jaap, Caimari Antoni, van Schothorst Evert M, Palou Andreu, Oliver Paula
Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears and CIBER de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Palma de Mallorca, Spain.
Human and Animal Physiology, Wageningen University, Wageningen, the Netherlands.
J Nutr Biochem. 2015 Apr;26(4):398-407. doi: 10.1016/j.jnutbio.2014.11.013. Epub 2015 Jan 13.
Peripheral blood mononuclear cells (PBMCs) are accessible in humans, and their gene expression pattern was shown to reflect overall physiological response of the body to a specific stimulus, such as diet. We aimed to study the impact of sustained intake (4months) of diets with an unbalanced macronutrient proportion (rich in fat or protein) administered isocalorically to a balanced control diet, as physiological stressors on PBMC whole-genome gene expression in rats, to better understand the effects of these diets on metabolism and health and to identify biomarkers of nutritional imbalance. Dietary macronutrient composition (mainly increased protein content) altered PBMC gene expression, with genes involved in immune response being the most affected. Intake of a high-fat (HF) diet decreased the expression of genes related to antigen recognition/presentation, whereas the high-protein (HP) diet increased the expression of these genes and of genes involved in cytokine signaling and immune system maturation/activation. Key energy homeostasis genes (mainly related to lipid metabolism) were also affected, reflecting an adaptive response to the diets. Moreover, HF diet feeding impaired expression of genes involved in redox balance regulation. Finally, we identified a common gene expression signature of 7 genes whose expression changed in the same direction in response to the intake of both diets. These genes, individually or together, constitute a potential risk marker of diet macronutrient imbalance. In conclusion, we newly show that gene expression analysis in PBMCs allows for detection of diet-induced physiological deviations that distinguish from a diet with a proper and equilibrated macronutrient composition.
外周血单核细胞（PBMCs）在人体中易于获取，并且其基因表达模式已被证明能够反映身体对特定刺激（如饮食）的整体生理反应。我们旨在研究等热量给予大鼠不平衡的常量营养素比例（富含脂肪或蛋白质）的饮食持续摄入（4个月）对平衡对照饮食的影响，作为生理应激源对大鼠PBMC全基因组基因表达的影响，以更好地理解这些饮食对代谢和健康的作用，并确定营养失衡的生物标志物。饮食中的常量营养素组成（主要是蛋白质含量增加）改变了PBMC的基因表达，其中参与免疫反应的基因受影响最大。高脂（HF）饮食的摄入降低了与抗原识别/呈递相关基因的表达，而高蛋白（HP）饮食则增加了这些基因以及参与细胞因子信号传导和免疫系统成熟/激活的基因的表达。关键的能量稳态基因（主要与脂质代谢相关）也受到影响，反映了对饮食的适应性反应。此外，HF饮食喂养损害了参与氧化还原平衡调节的基因的表达。最后，我们确定了7个基因的共同基因表达特征，其表达在两种饮食摄入后朝着相同方向变化。这些基因单独或共同构成了饮食常量营养素失衡的潜在风险标志物。总之，我们首次表明，PBMC中的基因表达分析能够检测出饮食诱导的生理偏差，这些偏差与具有适当且平衡的常量营养素组成的饮食不同。
