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交感神经促进剂可减轻肥胖而无不良心血管作用
作者:小柯机器人 发布时间:2020/5/13 23:52:22

英国牛津大学Ana I. Domingos和英国剑桥大学Gonçalo J.L. Bernardes研究组取得一项新突破。他们发现保守的脑交感神经促进剂可减轻肥胖,而无不良心血管作用。2020512日出版的《细胞-代谢》杂志发表了这项成果。

他们表明,安非他命(AMPH)的心脏副作用起源于大脑,可以通过聚乙二醇化(PEGyAMPH)加以规避,以排除其中心作用。PEGyAMPH不会进入大脑,并通过β2-肾上腺素能受体促进SNS活性,通过增加脂解作用和生热作用以及高热量散发来保护小鼠免于肥胖,这可以作为能量吸收器,在不改变食物摄入或运动能力的情况下增加能量消耗。因此,他们为新的完全外围的抗肥胖交感神经促进剂提供了原理性证明,这些新途径没有任何心血管和脑相关的副作用。

据悉,AMPH类抗肥胖药在大脑中起作用,可降低食欲并增加运动。它们起初还对心血管不利,尽管缺乏体内证据,但可归因于心脏中的直接交感神经作用。

附:英文原文

Title: Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects

Author: Inês Mahú, Andreia Barateiro, Eva Rial-Pensado, Noelia Martinéz-Sánchez, Sandra H. Vaz, Pedro M.S.D. Cal, Benjamin Jenkins, Tiago Rodrigues, Carlos Cordeiro, Miguel F. Costa, Raquel Mendes, Elsa Seixas, Mafalda M.A. Pereira, Nadiya Kubasova, Vitka Gres, Imogen Morris, Carolina Temporo, Marta Olivares, Yolanda Sanz, Albert Koulman, Francisco Corzana, Ana M. Sebastio, Miguel López, Gonalo J.L. Bernardes, Ana I. Domingos

Issue&Volume: 2020-05-12

Abstract: Anti-obesity drugs in the amphetamine (AMPH) class act in the brain to reduce appetiteand increase locomotion. They are also characterized by adverse cardiovascular effectswith origin that, despite absence of any in vivo evidence, is attributed to a direct sympathomimetic action in the heart. Here, weshow that the cardiac side effects of AMPH originate from the brain and can be circumventedby PEGylation (PEGyAMPH) to exclude its central action. PEGyAMPH does not enter thebrain and facilitates SNS activity via theβ2-adrenoceptor, protecting mice against obesity by increasing lipolysis and thermogenesis,coupled to higher heat dissipation, which acts as an energy sink to increase energy expenditure without altering food intake or locomotor activity.Thus, we provide proof-of-principle for a novel class of exclusively peripheral anti-obesitysympathofacilitators that are devoid of any cardiovascular and brain-related side effects.

DOI: 10.1016/j.cmet.2020.04.013

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30195-9

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx