小柯机器人

澳大利亚新南威尔士大学Vicky Wang-Wei Tsai课题组揭示GDF15通过瘦素途径使肥胖小鼠的体重和脂肪减少。相关论文于2023年7月10日发表在《细胞—代谢》杂志上。

在高脂肪饮食诱导的肥胖(HFD)小鼠中，GDF15和瘦素联合输注比单独治疗更能显著减轻体重和脂肪，这表明GDF15和瘦素之间存在增强作用。此外，肥胖、瘦素缺乏的ob/ob小鼠对GDF15的反应较弱，与使用竞争性瘦素拮抗剂治疗的正常小鼠一样。GDF15和瘦素在HFD小鼠中诱导的后脑神经元激活比单独使用任何一种疗效都更好。他们报道了胶质源性神经营养因子受体α样(GFRAL)-和表达LepR的神经元之间的广泛联系，并发现孤立束神经元核(NTS)中LepR的敲低可以减少GDF15介导的postrema区 (AP)神经元的激活。

总的来说，这些发现表明后脑中的瘦素信号通路增加了GDF15的代谢作用。

据介绍，GDF15通过后脑区AP和NTS调节其厌食作用，其受体GFRAL在这里表达。GDF15的作用可能与其他在肥胖中升高的食欲调节因子相互作用，如瘦素。

附：英文原文

Title: GDF15 enhances body weight and adiposity reduction in obese mice by leveraging the leptin pathway

Author: Samuel N. Breit, Rakesh Manandhar, Hong-Ping Zhang, Michelle Lee-Ng, David A. Brown, Vicky Wang-Wei Tsai

Issue&Volume: 2023-07-10

Abstract: GDF15 regulates its anorexic effects through the hindbrain area postrema (AP) andnucleus of the solitary tract (NTS) neurons where its receptor, glial-derived neurotrophicfactor receptor alpha-like (GFRAL), is expressed. The actions of GDF15 may interactwith other appetite regulators elevated in obesity, such as leptin. Here, we reportthat in mice with high-fat-diet-induced obesity (HFD), the combined infusion of GDF15and leptin causes significantly greater weight and adiposity loss than either treatmentalone, indicating potentiation between GDF15 and leptin. Furthermore, obese, leptin-deficientob/ob mice are less responsive to GDF15, as are normal mice treated with a competitiveleptin antagonist. GDF15 and leptin induce more hindbrain neuronal activation in HFDmice than either treatment alone does. We report extensive connections between GFRAL-and LepR-expressing neurons and find LepR knockdown in the NTS to reduce the GDF15-mediatedactivation of AP neurons. Overall, these findings suggest that leptin signaling pathwaysin the hindbrain increase GDF15’s metabolic actions.

DOI: 10.1016/j.cmet.2023.06.009

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00219-X

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
官方网址：https://www.cell.com/cell-metabolism/home
投稿链接：https://www.editorialmanager.com/cell-metabolism/default.aspx