Badoud Flavia, Brewer Dyanne, Charchoglyan Armen, Cuthbertson Daniel J, Mutch David M
1 Department of Human Health & Nutritional Sciences, University of Guelph , Guelph, Ontario, Canada .
2 Department of Molecular and Cellular Biology, University of Guelph , Guelph, Ontario, Canada .
OMICS. 2017 Jul;21(7):371-379. doi: 10.1089/omi.2017.0049. Epub 2017 Jun 15.
White adipose tissue (WAT) plays a central role in whole-body energy homeostasis through storage and release of fatty acids. A deeper understanding of the complex and highly integrated pathways regulating WAT fatty acid metabolism, and how they are altered with obesity, is necessary for diagnostic and therapeutic innovations in nutritional disorders. In this multi-omics study, we investigated the influence of obesity on fatty acid metabolism in human subcutaneous adipose tissue (SAT) using an approach that integrated transcriptomic, peptidomic, and fatty acid analyses. Notably, all analyses were conducted in the same adipose tissue sample from each participant, thus minimizing the chance of spurious results. In a sample of SAT from the periumbilical abdominal region of obese (n = 11, mean body mass index [BMI] = 35.0 ± 1.2 kg/m) and lean subjects (n = 9, mean BMI = 22.1 ± 0.5 kg/m), we found that obese SAT tended to have higher relative amounts of specific monounsaturated fatty acids and n-6 polyunsaturated fatty acids, and lower amounts of saturated fatty acids (p < 0.05). These changes were associated with differential regulation of lipogenic and lipolytic pathways in obese SAT. Fatty acid analysis showed changes in estimated fatty acid desaturase and elongase activities between lean and obese SAT (p < 0.05). Biomarkers of lipogenesis (e.g., fatty acid synthase protein) were differentially regulated between lean and obese SAT. These changes were noted in conjunction with increases in extracellular matrix remodeling proteins. Transcriptomic data revealed that the key regulators of lipolysis were reduced in obese SAT. This integrative multi-omics analysis collectively shows that obese SAT has a distinct fatty acid signature compared to lean SAT and the pathways underlying fatty acid metabolism are broadly regulated at the level of gene expression and protein abundance.
白色脂肪组织（WAT）通过脂肪酸的储存和释放，在全身能量稳态中发挥核心作用。深入了解调节WAT脂肪酸代谢的复杂且高度整合的途径，以及它们如何随肥胖而改变，对于营养失调的诊断和治疗创新至关重要。在这项多组学研究中，我们采用整合转录组学、肽组学和脂肪酸分析的方法，研究肥胖对人皮下脂肪组织（SAT）中脂肪酸代谢的影响。值得注意的是，所有分析均在来自每位参与者的同一脂肪组织样本中进行，从而将虚假结果的可能性降至最低。在取自肥胖（n = 11，平均体重指数[BMI] = 35.0 ± 1.2 kg/m²）和瘦受试者（n = 9，平均BMI = 22.1 ± 0.5 kg/m²）脐周腹部区域的SAT样本中，我们发现肥胖SAT中特定单不饱和脂肪酸和n-6多不饱和脂肪酸的相对含量往往较高，而饱和脂肪酸含量较低（p < 0.05）。这些变化与肥胖SAT中脂肪生成和脂肪分解途径的差异调节有关。脂肪酸分析显示，瘦SAT和肥胖SAT之间估计的脂肪酸去饱和酶和延长酶活性存在变化（p < 0.05）。脂肪生成的生物标志物（如脂肪酸合酶蛋白）在瘦SAT和肥胖SAT之间受到差异调节。这些变化与细胞外基质重塑蛋白的增加同时出现。转录组学数据显示，肥胖SAT中脂肪分解的关键调节因子减少。这项综合多组学分析共同表明，与瘦SAT相比，肥胖SAT具有独特的脂肪酸特征，并且脂肪酸代谢的潜在途径在基因表达和蛋白质丰度水平上受到广泛调节。
