Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1297, Institute of Metabolic and Cardiovascular Diseases, Team Metabolic Disorders and Diabesity, 31400, Toulouse, France.
Université de Toulouse, UMR1297, Institute of Metabolic and Cardiovascular Diseases, Paul Sabatier University, 31400, Toulouse, France.
J Clin Endocrinol Metab. 2022 Jan 1;107(1):e130-e142. doi: 10.1210/clinem/dgab621.
Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes.
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).
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.
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.
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.
脂肪组织（AT）转录组研究提供了对体重和相关生物临床环境变化适应的整体图景。
实施 AT 基因表达谱分析，并研究在两步饮食干预（DI）的 3 个阶段中生物临床参数变化与 AT 基因表达之间的联系。
对来自 556 名个体的 1051 个样本进行 AT 转录组谱分析，这些个体参加了一项减肥干预（8 周每天 800 卡路里的低热量饮食（LCD）），随后进行了 6 个月的随意 DI。使用 QuantSeq 测序获得的转录组谱与 Illumina RNAseq 进行基准测试。逆转录定量聚合酶链反应用于进一步确认关联。使用新鲜分离的细胞和 THP-1 细胞系评估细胞特异性。
在 LCD 期间，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 水平变化相关。在这个模块中，BMI 的变化与编码分泌蛋白（GDF15、CCL3 和 SPP1）的基因表达的变化呈负相关。通过 DI 的所有阶段，GDF15 的变化与 SPP1、CCL3、LIPA 和 CD68 的变化相关。进一步的特征表明，这些基因是巨噬细胞特异性的（LIPA、CD68 和 GDF15 在抗炎性巨噬细胞中表达），并且 GDF15 也在脂肪前体细胞中表达。
网络分析确定了一个新的 AT 特征，即 GDF15 在卡路里限制诱导的体重减轻时上调，同时伴随着巨噬细胞标志物。在 AT 中，GDF15 在脂肪前体细胞和巨噬细胞中表达，是抗炎细胞的标志。
