Peripheral blood mononuclear cells gene expression reflects adaptive response and metabolic damage associated to the intake of diets with an unbalanced proportion of macronutrients

Gene expression studies in peripheral blood mononuclear cells (PBMC) can provide knowledge that would be difficult to obtain using other types of biological samples, as these cells can reflect overall response of the body to a specific stimulus, such as diet. Here, we aimed to study the impact of sustained intake of isocaloric diets with an unbalanced macronutrient proportion (rich in fat or protein) on PBMC gene expression in rats using transcriptomics, to better understand the effects of these diets on metabolism and health. Macronutrient diet composition (especially increased protein content) affected PBMC gene expression. An important effect was observed in immune response-related genes. High protein (HP) diet produced an activation of genes mainly related to antigen recognition/presentation, whereas the high fat (HF) diet was more related to a decreased expression of these genes. Key energy homeostasis genes (mainly involved in lipid metabolism) were also affected, reflecting a nutritional adaptive response to the diets. Decreased Dhrs3 and increased Pref-1/Dlk1 expression observed in HP-fed animals reflects a lower lipogenic capacity. In addition, HF diet affected the expression of genes related to insulin resistance/signaling (Msra/Slc9a6, Asb6), hypoxia (Akap12), cardiovascular problems (Ethe1, Lr11), cognitive impairment (Tmcc2) and tumorigenesis (Ddx17, Phb, Rnasen/Drosha, and Tsc2). HP diet also impaired the expression of genes related to glucose metabolism and insulinemia (Glut-4/Slc2a4, Sfxn5, Slc16a1), but positively affected genes involved in liver function (Clec4f and St6galnac3) and cardiovascular protection (Sort1). In conclusion, gene expression analysis in PBMC can provide information that could be useful to detect metabolic deviations and health consequences of diets with an unbalanced macronutrient composition.对外周血单个核细胞（peripheral blood mononuclear cells, PBMC）进行基因表达研究，可获取其他生物样本难以获得的研究结论，因该类细胞能够反映机体对特定刺激（如膳食）的整体应答状态。本研究借助转录组学技术，探究长期摄入宏营养素比例失衡（高脂或高蛋白）的等热量膳食对大鼠PBMC基因表达的影响，以期深入解析此类膳食对机体代谢与健康的作用。膳食宏营养素组成（尤其是蛋白质含量升高）可影响PBMC基因表达，其中与免疫应答相关的基因受到的调控尤为显著。高蛋白（high protein, HP）膳食可激活主要与抗原识别/呈递相关的基因，而高脂（high fat, HF）膳食则更倾向于降低此类基因的表达水平。核心能量稳态相关基因（主要参与脂质代谢过程）同样受到调控，这反映了机体对膳食的营养适应性应答。在HP膳食喂养的大鼠中观察到的Dhrs3表达下调与Pref-1/Dlk1表达上调，反映出机体的脂肪合成能力降低。此外，HF膳食可调控与胰岛素抵抗/信号通路（Msra/Slc9a6、Asb6）、缺氧（Akap12）、心血管异常（Ethe1、Lr11）、认知功能损伤（Tmcc2）以及肿瘤发生（Ddx17、Phb、Rnasen/Drosha与Tsc2）相关的基因表达。HP膳食还会削弱与糖代谢及胰岛素血症相关的基因（Glut-4/Slc2a4、Sfxn5、Slc16a1）的表达，但可正向调控参与肝功能（Clec4f与St6galnac3）及心血管保护（Sort1）的基因。综上，对PBMC进行基因表达分析，可为检测宏营养素比例失衡膳食引发的代谢异常与健康损害提供有效信息。