Institut Cochin, Inserm U1016, CNRS UMR 8104, Université Paris Cité, F-75014 Paris, France.
Unité de Biologie Fonctionnelle et Adaptative, Université Paris Cité, CNRS, 75013 Paris, France.
JCI Insight. 2024 Apr 2;9(9):e168418. doi: 10.1172/jci.insight.168418.
The importance of the proper localization of most receptors at the cell surface is often underestimated, although this feature is essential for optimal receptor response. Endospanin 1 (Endo1) (also known as OBRGRP or LEPROT) is a protein generated from the same gene as the human leptin receptor and regulates the trafficking of proteins to the surface, including the leptin receptor. The systemic role of Endo1 on whole-body metabolism has not been studied so far. Here, we report that general Endo1-KO mice fed a high-fat diet develop metabolically healthy obesity with lipid repartitioning in organs and preferential accumulation of fat in adipose tissue, limited systematic inflammation, and better controlled glucose homeostasis. Mechanistically, Endo1 interacts with the lipid translocase CD36, thus regulating its surface abundance and lipid uptake in adipocytes. In humans, the level of Endo1 transcripts is increased in the adipose tissue of patients with obesity, but low levels rather correlate with a profile of metabolically healthy obesity. We suggest here that Endo1, most likely by controlling CD36 cell surface abundance and lipid uptake in adipocytes, dissociates obesity from diabetes and that its absence participates in metabolically healthy obesity.
大多数受体在细胞表面的正确定位的重要性经常被低估，尽管这一特征对于最佳受体反应至关重要。内脂素 1（Endo1）（也称为 OBRGRP 或 LEPROT）是一种从人类瘦素受体基因产生的蛋白质，它调节蛋白质向表面的运输，包括瘦素受体。目前还没有研究内脂素 1 在全身代谢中的系统作用。在这里，我们报告说，喂食高脂肪饮食的普通内脂素 1-KO 小鼠会发展出代谢健康的肥胖症，其器官中的脂质重新分布，并优先在脂肪组织中积累脂肪，系统炎症有限，葡萄糖稳态得到更好的控制。从机制上讲，内脂素 1 与脂质转运蛋白 CD36 相互作用，从而调节其在脂肪细胞中的表面丰度和脂质摄取。在人类中，肥胖症患者脂肪组织中的内脂素 1 转录本水平升高，但低水平与代谢健康肥胖症的特征相关。在这里，我们提出内脂素 1 可能通过控制脂肪细胞中 CD36 的细胞表面丰度和脂质摄取，将肥胖与糖尿病分离，并且其缺失参与了代谢健康肥胖症。
