Comas Ferran, Martínez Cristina, Sabater Mònica, Ortega Francisco, Latorre Jessica, Díaz-Sáez Francisco, Aragonés Julian, Camps Marta, Gumà Anna, Ricart Wifredo, Fernández-Real José Manuel, Moreno-Navarrete José María
Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomèdica de Girona, Girona, Spain.
CIBEROBN (CB06/03/010), Instituto de Salud Carlos III, Madrid, Spain.
Front Physiol. 2019 Jan 31;10:39. doi: 10.3389/fphys.2019.00039. eCollection 2019.
Nrg4 expression has been linked to brown adipose tissue activity and browning of white adipocytes in mice. Here, we aimed to investigate whether these observations could be translated to humans by investigating mRNA and markers of brown/beige adipocytes in human visceral (VAT) and subcutaneous adipose tissue (SAT). We also studied the possible association of with insulin action. SAT and VAT and markers of brown/beige ()-related gene expression were analyzed in two independent cohorts ( = 331 and = 59). Insulin resistance/sensitivity was measured using HOMA and glucose infusion rate during euglycemic hyperinsulinemic clamp. In both cohort 1 and cohort 2, and thermogenic/beige-related gene expression were significantly increased in VAT compared to SAT. Adipogenic-related genes followed an opposite pattern. In cohort 1, VAT gene expression was positively correlated with BMI and expression of , and negatively with adipogenic (, and )- and inflammatory ()-related genes. In SAT, gene expression was negatively correlated with HOMA and positively with and gene expression. Multiple linear regression analysis revealed that expression of gene was the best predictor of gene expression in both VAT and SAT. Specifically, and gene expression was significantly increased in VAT, but not in SAT stromal vascular fraction cells ( < 0.001). In cohort 2, the significant association between and gene expression in both VAT and SAT was confirmed, and SAT gene expression also was positively correlated with insulin action and the expression of . Current findings suggest gene expression as a novel marker of beige adipocytes in human adipose tissue.
在小鼠中，Nrg4的表达与棕色脂肪组织活性以及白色脂肪细胞的棕色化有关。在此，我们旨在通过研究人类内脏脂肪组织（VAT）和皮下脂肪组织（SAT）中棕色/米色脂肪细胞的mRNA和标志物，来探究这些观察结果是否适用于人类。我们还研究了其与胰岛素作用之间可能存在的关联。在两个独立队列（队列1 = 331人，队列2 = 59人）中分析了SAT和VAT以及棕色/米色（UCP1）相关基因表达的标志物。使用稳态模型评估法（HOMA）和正常血糖高胰岛素钳夹期间的葡萄糖输注率来测量胰岛素抵抗/敏感性。在队列1和队列2中，与SAT相比，VAT中的UCP1和产热/米色相关基因表达均显著增加。脂肪生成相关基因则呈现相反的模式。在队列1中，VAT中UCP1基因表达与体重指数（BMI）以及PPARγ的表达呈正相关，而与脂肪生成（FABP4、LPL和ADIPOQ）和炎症（IL6）相关基因呈负相关。在SAT中，UCP1基因表达与HOMA呈负相关，与CD137和TOMM40基因表达呈正相关。多元线性回归分析显示，UCP1基因表达是VAT和SAT中PPARγ基因表达的最佳预测指标。具体而言，UCP1和PPARγ基因表达在VAT中显著增加，但在SAT的基质血管成分细胞中未增加（P < 0.001）。在队列2中，证实了VAT和SAT中UCP1与PPARγ基因表达之间存在显著关联，并且SAT中UCP1基因表达也与胰岛素作用以及CD137的表达呈正相关。目前的研究结果表明，UCP1基因表达是人类脂肪组织中米色脂肪细胞的一种新型标志物。
