Department of Physiology, Keimyung University School of Medicine, Daegu 42601, Korea.
Department of Internal Medicine, School of Medicine, Catholic University of Daegu, Daegu 42472, Korea.
Biomolecules. 2020 Feb 17;10(2):314. doi: 10.3390/biom10020314.
Adpsin is an adipokine that stimulates insulin secretion from β-cells and improves glucose tolerance. Its expression has been found to be markedly reduced in obese animals. However, it remains unclear what factors lead to downregulation of adipsin in the context of obesity. Endoplasmic reticulum (ER) stress response is activated in various tissues under obesity-related conditions and can induce transcriptional reprogramming. Therefore, we aimed to investigate the relationship between adipsin expression and ER stress in adipose tissues during obesity. We observed that obese mice exhibited decreased levels of adipsin in adipose tissues and serum and increased ER stress markers in adipose tissues compared to lean mice. We also found that ER stress suppressed adipsin expression via adipocytes-intrinsic mechanisms. Moreover, the ER stress-mediated downregulation of adipsin was at least partially attributed to decreased expression of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor in the regulation of adipocyte function. Finally, treatment with chemical chaperones recovered the ER stress-mediated downregulation of adipsin and PPARγ in vivo and in vitro. Our findings suggest that activated ER stress in adipose tissues is an important cause of the suppression of adipsin expression in the context of obesity.
脂联素是一种脂肪细胞因子，可刺激β细胞分泌胰岛素并改善葡萄糖耐量。研究发现，肥胖动物的脂联素表达明显降低。然而，在肥胖的情况下，导致脂联素下调的因素仍不清楚。内质网（ER）应激反应在肥胖相关条件下的各种组织中被激活，并能诱导转录重编程。因此，我们旨在研究肥胖时脂肪组织中脂联素表达与 ER 应激之间的关系。我们观察到肥胖小鼠的脂肪组织和血清中的脂联素水平降低，脂肪组织中的 ER 应激标志物增加，而与瘦小鼠相比。我们还发现 ER 应激通过脂肪细胞内在机制抑制脂联素的表达。此外，至少部分原因是过氧化物酶体增殖物激活受体γ（PPARγ）的表达减少，PPARγ是调节脂肪细胞功能的关键转录因子，这种 ER 应激介导的脂联素下调。最后，化学伴侣处理在体内和体外恢复了 ER 应激介导的脂联素和 PPARγ的下调。我们的研究结果表明，脂肪组织中激活的 ER 应激是肥胖时脂联素表达抑制的一个重要原因。
