小柯机器人

奥地利维也纳医科大学Thomas Scherer团队的研究发现，在人体内瘦素通过迷走神经机制增加肝脏甘油三酯的转运。该研究于2022年10月10日发表于国际学术期刊《细胞—代谢》杂志。

在这项随机的安慰剂对照交叉试验（EudraCT Nr. 2017-003014-22）中，研究人员测试了啮齿动物迷走神经元降肝脂机制是否调节人体的肝脂代谢。单米瘦素注射刺激了肝极低密度脂蛋白-甘油三酯（VLDL-TG）的分泌（主要终点）并降低了禁食瘦男性（n=13，年龄范围20-38岁）的肝脂含量，但在代谢健康的肝移植受者（n=9，年龄范围26-62岁）中未能实现这一点，这代表了肝去神经支配模型。

在一个独立的瘦男性队列中（n=10，年龄范围23-31岁），通过改良的假喂养进行迷走神经刺激复制了米瘦素对VLDL-TG分泌的影响。因此，该研究表明瘦素具有抗脂肪特性，通过脑-迷走神经-肝脏轴刺激肝脏VLDL-TG的输出，而与食物摄入无关。

据了解，重组人瘦素（metreleptin）可降低脂肪营养不良患者、非酒精性脂肪肝患者和相对低瘦素血症患者的肝脂含量，而与厌食症无关。在啮齿动物中，大脑瘦素信号传导增加了VLDL-TG的分泌，并通过迷走神经降低肝脂质含量。

附：英文原文

Title: Leptin increases hepatic triglyceride export via a vagal mechanism in humans

Author: Matthus Metz, Marianna Beghini, Peter Wolf, Lorenz Pfleger, Martina Hackl, Magdalena Bastian, Angelika Freudenthaler, Jürgen Harreiter, Maximilian Zeyda, Sabina Baumgartner-Parzer, Rodrig Marculescu, Nara Marella, J. Thomas Hannich, Georg Gyri, Gabriela Berlakovich, Michael Roden, Michael Krebs, Robert Risti, Aivar Lokene, Michael Trauner, Alexandra Kautzky-Willer, Martin Krák, Herbert Stangl, Clemens Fürnsinn, Thomas Scherer

Issue&Volume: 2022-10-10

Abstract: Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients withlipodystrophy and overweight patients with non-alcoholic fatty liver disease and relativehypoleptinemia independent of its anorexic action. In rodents, leptin signaling inthe brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretionand reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlledcrossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanismregulates hepatic lipid metabolism in humans. A single metreleptin injection stimulatedhepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted,lean men (n = 13, age range 20–38 years) but failed to do so in metabolically healthyliver transplant recipients (n = 9, age range 26–62 years) who represent a model forhepatic denervation. In an independent cohort of lean men (n = 10, age range 23–31years), vagal stimulation by modified sham feeding replicated the effects of metreleptinon VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic propertiesthat are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liveraxis.

DOI: 10.1016/j.cmet.2022.09.020

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00410-7

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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