Nutrigenomics, Biomarkers and Risk Evaluation (NuBE) Group, University of the Balearic Islands (UIB), Palma, Spain.
Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain.
Sci Rep. 2021 Sep 15;11(1):18329. doi: 10.1038/s41598-021-96981-6.
Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. In this pilot proof-of-concept study we analysed in humans if, as we previously suggested in rodents, PBMC could be a surrogate tissue to study overweight/obesity impact on lipid metabolism. Pre-selected key lipid metabolism genes based in our previous preclinical studies were analysed in PBMC of normoglycemic normal-weight (NW), and overweight-obese (OW-OB) subjects before and after a 6-month weight-loss plan. PBMC mRNA levels of CPT1A, FASN and SREBP-1c increased in the OW-OB group, according with what described in liver and adipose tissue of humans with obesity. This altered expression pattern was related to increased adiposity and early signs of metabolic impairment. Greater weight loss and/or metabolic improvement as result of the intervention was related to lower CPT1A, FASN and SREBP-1c gene expression in an adjusted linear mixed-effects regression analysis, although no gene expression recovery was observed when considering mean comparisons. Thus, human PBMC reflect lipid metabolism expression profile of energy homeostatic tissues, and early obesity-related alterations in metabolic at-risk subjects. Further studies are needed to understand PBMC usefulness for analysis of metabolic recovery in weigh management programs.
外周血单核细胞 (PBMC) 广泛用作营养/肥胖研究中的生物标志物来源，因为它们反映了内部组织的基因表达谱。在这项初步概念验证研究中，我们分析了人类是否像我们之前在啮齿动物中所建议的那样，PBMC 可以作为研究超重/肥胖对脂质代谢影响的替代组织。根据我们之前的临床前研究，选择了关键的脂质代谢基因，并在血糖正常的正常体重 (NW) 和超重肥胖 (OW-OB) 受试者进行 6 个月减肥计划前后进行了分析。OW-OB 组中 PBMC 的 CPT1A、FASN 和 SREBP-1c 的 mRNA 水平增加，这与肥胖人群的肝脏和脂肪组织中描述的情况一致。这种改变的表达模式与肥胖相关的脂肪增加和代谢早期损伤有关。调整后的线性混合效应回归分析显示，干预后体重减轻和/或代谢改善与 CPT1A、FASN 和 SREBP-1c 基因表达降低有关，但在考虑平均比较时未观察到基因表达恢复。因此，人类 PBMC 反映了能量稳态组织的脂质代谢表达谱，以及代谢风险增加的肥胖相关早期改变。需要进一步研究以了解 PBMC 在体重管理计划中分析代谢恢复的有用性。
