Toxicology and Multipurpose Lab, Anti Doping Laboratory Qatar, Sports City, Doha, Qatar.
Department of Economics, Mathematics and Statistics, Birkbeck, University of London, London, WC1E 7HX, UK.
J Transl Med. 2018 Jun 26;16(1):175. doi: 10.1186/s12967-018-1548-x.
Lipid intermediates produced during triacylglycerols (TAGs) synthesis and lipolysis in adipocytes interfere with the intracellular insulin signaling pathway and development of insulin resistance. This study aims to compare TAG species and their fatty acid composition in adipose tissues from insulin sensitive (IS), insulin resistant (IR) and type 2 diabetes mellitus (T2DM) obese individuals.
Human subcutaneous and omental adipose tissue biopsies were obtained from 64 clinically characterized obese individuals during weight reduction surgery. TAGs were extracted from the adipose tissues using the Bligh and Dyer method, then were subjected to non-aqueous reverse phase ultra-high performance liquid chromatography and full scan mass spectrometry acquisition and data dependent MS/MS on LTQ dual cell linear ion trap. TAGs and their fatty acid contents were identified and compared between IS, IR and T2DM individuals and their levels were correlated with metabolic traits of participants and the adipogenic potential of preadipocyte cultures established from their adipose tissues.
Data revealed 76 unique TAG species in adipose tissues identified based on their exact mass. Analysis of TAG levels revealed a number of TAGs that were significantly altered with disease progression including C46:4, C48:5, C48:4, C38:1, C50:3, C40:2, C56:3, C56:4, C56:7 and C58:7. Enrichment analysis revealed C12:0 fatty acid to be associated with TAGs least abundant in T2DM whereas C18:3 was found in both depleted and enriched TAGs in T2DM. Significant correlations of various adipose tissue-derived TAG species and metabolic traits were observed, including age and body mass index, systemic total cholesterol, TAGs, and interleukin-6 in addition to adipogenic potential of preadipocytes derived from the same adipose tissues.
Pilot data suggest that adipose tissues from obese IR and T2DM individuals exhibit TAG-specific signatures that may contribute to their increased risk compared to their IS counterparts. Future experiments are warranted to investigate the functional relevance of these specific lipidomic profiles.
脂肪细胞中三酰基甘油(TAGs)合成和脂肪分解过程中产生的脂质中间体干扰细胞内胰岛素信号通路并导致胰岛素抵抗的发生。本研究旨在比较胰岛素敏感（IS）、胰岛素抵抗（IR）和 2 型糖尿病（T2DM）肥胖个体的脂肪组织中的 TAG 种类及其脂肪酸组成。
在减重手术期间，从 64 名临床特征明确的肥胖个体中获取人皮下和网膜脂肪组织活检。采用 Bligh 和 Dyer 法从脂肪组织中提取 TAG，然后进行非水反相超高效液相色谱和全扫描质谱采集，并在 LTQ 双池线性离子阱上进行数据依赖 MS/MS。在 IS、IR 和 T2DM 个体之间对 TAG 及其脂肪酸含量进行鉴定和比较，并将其水平与参与者的代谢特征和从其脂肪组织建立的前体脂肪细胞培养的成脂潜能相关联。
基于精确质量，数据揭示了脂肪组织中 76 种独特的 TAG 种类。TAG 水平分析显示，随着疾病的进展，许多 TAG 发生了显著改变，包括 C46:4、C48:5、C48:4、C38:1、C50:3、C40:2、C56:3、C56:4、C56:7 和 C58:7。富集分析显示，C12:0 脂肪酸与 T2DM 中含量最低的 TAG 相关，而 C18:3 则存在于 T2DM 中耗尽和富集的 TAG 中。观察到各种脂肪组织衍生的 TAG 种类与代谢特征之间存在显著相关性，包括年龄和体重指数、全身总胆固醇、TAG 和白细胞介素-6 以及来自相同脂肪组织的前体脂肪细胞的成脂潜能。
初步数据表明，与 IS 个体相比，肥胖的 IR 和 T2DM 个体的脂肪组织表现出特定的 TAG 特征，这可能导致他们的风险增加。需要进行进一步的实验来研究这些特定脂质组学特征的功能相关性。
