网络分析揭示了饮食诱导的体重减轻期间脂肪组织GDF15和BMI变化之间的负相关
Network analyses reveal negative link between changes in adipose tissue GDF15 and BMI during dietary-induced weight loss
摘要：
脂肪组织（AT）转录组研究提供了适应体重和相关生物临床环境变化的整体图片。目的应用AT基因表达谱分析技术，探讨2阶段饮食干预（DI）3个步骤中AT基因表达与临床生物学参数变化的关系。方法通过对1051个样本进行测序获得AT转录组谱，这些样本对应于556名参加减肥干预（8周低热量饮食（LCD），800 kcal/天）的不同个体，随后是6个月的随意随机DI。用QuantSeq测序获得的转录组谱以Illumina RNAseq为基准。逆转录定量聚合酶链反应被用来进一步确认协会。使用新鲜分离的细胞和THP-1细胞系评估细胞特异性。结果在LCD过程中，发现了5个模块，其中3个模块至少包含1个生物临床变量。体重指数（BMI）的变化与具有炎症反应特征的基因的mRNA水平的变化有关。在该模块中，BMI的变化与编码分泌蛋白（GDF 15、CCL 3和SPP 1）的基因表达的变化呈负相关。在DI的所有阶段，GDF 15的变化与SPP 1、CCL 3、LIPA和CD 68的变化相关。进一步的表征表明，这些基因对巨噬细胞是特异性的（LIPA、CD 68和GDF 15在抗炎巨噬细胞中表达），GDF 15也在前脂肪细胞中表达。结论网络分析确定了一种新的AT特征，其中GDF 15随着热量限制诱导的体重减轻而上调，伴随着巨噬细胞标志物。在AT中，GDF 15在前脂肪细胞和巨噬细胞中表达，在那里它是抗炎细胞的标志。
英文摘要：
Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. Objective To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). Methods AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. Results During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. Conclusion Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
