Institute of Nutrition and Food Technology (INTA), University of Chile, Santiago 7830490, Chile.
Department of Nutrition and Public Health, Faculty of Health Sciences, University of Bío-Bío, Andrés Bello 720, Chillán 3800708, Chile.
Int J Mol Sci. 2020 Oct 15;21(20):7617. doi: 10.3390/ijms21207617.
Autophagy is upregulated in adipose tissue (AT) from people with obesity. We showed that activation of the calcium-sensing receptor (CaSR) elevates proinflammatory cytokines through autophagy in preadipocytes. Our aim is to understand the role of CaSR on autophagy in AT from humans with obesity. We determined mRNA and protein levels of CaSR and markers of autophagy by qPCR and western blot in human visceral AT explants or isolated primary preadipocytes (60 donors: 72% female, 23-56% body fat). We also investigated their association with donors' anthropometric variables. Donors' % body fat and CaSR mRNA expression in AT were correlated (r = 0.44, < 0.01). CaSR expression was associated with mRNA levels of the autophagy markers (r = 0.37, < 0.01), (r = 0.29, < 0.05) and (r = 0.40, < 0.01). CaSR activation increased and mRNA expression in AT. CaSR activation also upregulated LC3II by ~50%, an effect abolished by the CaSR inhibitor. Spermine (CaSR agonist) regulates LC3II through the ERK1/2 pathway. Structural equation model analysis suggests a link between donors' AT CaSR expression, AT autophagy and expression of Tumor Necrosis Factor alpha TNF-α. CaSR expression in visceral AT is directly associated with % body fat, and CaSR activation may contribute to obesity-related disruption in AT autophagy.
自噬在肥胖人群的脂肪组织（AT）中上调。我们表明，钙敏感受体（CaSR）的激活通过前体脂肪细胞中的自噬作用升高促炎细胞因子。我们的目的是了解肥胖人群中 CaSR 对 AT 自噬的作用。我们通过 qPCR 和 Western blot 测定了人类内脏 AT 外植体或分离的原代前体脂肪细胞中 CaSR 和自噬标志物的 mRNA 和蛋白水平（60 个供体：女性占 72%，体脂率 23-56%）。我们还研究了它们与供体人体测量变量的相关性。供体 AT 中的 %体脂和 CaSR mRNA 表达呈正相关（r = 0.44， < 0.01）。CaSR 表达与自噬标志物的 mRNA 水平相关（r = 0.37， < 0.01）、（r = 0.29， < 0.05）和（r = 0.40， < 0.01）。CaSR 激活增加了 AT 中 和 的 mRNA 表达。CaSR 激活还通过 ~50%上调了 LC3II，该效应被 CaSR 抑制剂所消除。亚精胺（CaSR 激动剂）通过 ERK1/2 途径调节 LC3II。结构方程模型分析表明，供体 AT CaSR 表达、AT 自噬和肿瘤坏死因子-α TNF-α 表达之间存在联系。内脏 AT 中的 CaSR 表达与体脂%直接相关，CaSR 激活可能导致肥胖相关的 AT 自噬破坏。
