Iqbal Zohaib, Fachim Helene A, Gibson J Martin, Baricevic-Jones Ivona, Campbell Amy E, Geary Bethany, Donn Rachelle P, Hamarashid Dashne, Syed Akheel, Whetton Anthony D, Soran Handrean, Heald Adrian H
The School of Medicine and Manchester Academic Health Sciences Centre, Manchester University, Manchester M13 9PL, UK.
Department of Endocrinology, Diabetes and Metabolism, Salford Royal Foundation Trust, Salford M6 8HD, UK.
J Clin Med. 2021 Aug 18;10(16):3659. doi: 10.3390/jcm10163659.
Bariatric surgery (BS) results in metabolic pathway recalibration. We have identified potential biomarkers in plasma of people achieving type 2 diabetes mellitus (T2DM) remission after BS. Longitudinal analysis was performed on plasma from 10 individuals following Roux-en-Y gastric bypass ( = 7) or sleeve gastrectomy ( = 3). Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was done on samples taken at 4 months before (baseline) and 6 and 12 months after BS. Four hundred sixty-seven proteins were quantified by SWATH-MS. Principal component analysis resolved samples from distinct time points after selection of key discriminatory proteins: 25 proteins were differentially expressed between baseline and 6 months post-surgery; 39 proteins between baseline and 12 months. Eight proteins (SHBG, TF, PRG4, APOA4, LRG1, HSPA4, EPHX2 and PGLYRP) were significantly different to baseline at both 6 and 12 months post-surgery. The panel of proteins identified as consistently different included peptides related to insulin sensitivity (SHBG increase), systemic inflammation (TF and HSPA4-both decreased) and lipid metabolism (APOA4 decreased). We found significant changes in the proteome for eight proteins at 6- and 12-months post-BS, and several of these are key components in metabolic and inflammatory pathways. These may represent potential biomarkers of remission of T2DM.
减重手术(BS)可导致代谢途径重新校准。我们已经在接受BS后实现2型糖尿病(T2DM)缓解的人群血浆中鉴定出潜在的生物标志物。对10名接受Roux-en-Y胃旁路手术(n = 7)或袖状胃切除术(n = 3)的个体的血浆进行了纵向分析。在BS前4个月(基线)以及BS后6个月和12个月采集的样本上进行了所有理论碎片离子谱质谱(SWATH-MS)的连续窗口采集。通过SWATH-MS对467种蛋白质进行了定量分析。在选择关键的鉴别性蛋白质后,主成分分析解析了来自不同时间点的样本:25种蛋白质在基线和术后6个月之间差异表达;39种蛋白质在基线和术后12个月之间差异表达。8种蛋白质(性激素结合球蛋白、转铁蛋白、润滑蛋白4、载脂蛋白A4、富含亮氨酸α-2糖蛋白1、热休克蛋白A4、环氧化物水解酶2和肽聚糖识别蛋白)在术后6个月和12个月时均与基线有显著差异。被确定为始终存在差异的蛋白质组包括与胰岛素敏感性相关的肽(性激素结合球蛋白增加)、全身炎症(转铁蛋白和热休克蛋白A4均降低)和脂质代谢(载脂蛋白A4降低)。我们发现,在BS后6个月和12个月时,8种蛋白质的蛋白质组有显著变化,其中几种是代谢和炎症途径的关键成分。这些可能代表T2DM缓解的潜在生物标志物。