小柯机器人

瘦素-BDNF途径可调控脂肪组织交感神经
2020-07-24 16:39

美国洛克菲勒大学Jeffrey Friedman和Ken H. Loh研究组合作取得新进展。他们发现瘦素-BDNF途径调控脂肪组织的交感神经。该项研究成果发表在2020年7月22日出版的《自然》杂志上。

研究人员发现,瘦素基因(ob)敲除小鼠,以及瘦素抵抗饮食诱导的肥胖小鼠,表现出皮下白色和棕色脂肪组织交感神经支配的显著减少。ob / ob小鼠的慢性瘦素治疗,可恢复脂肪组织的交感神经,这反过来对于纠正相关功能缺陷是必需的。瘦素对神经支配的作用是通过下丘脑弓状核中的刺骨相关肽和促黑素皮质素神经元介导的。

在任一群体中编码瘦素受体的基因的缺失,导致脂肪神经支配的减少。这些刺骨相关肽和促黑素皮质素神经元,通过下丘脑室旁核(BDNFPVH)中脑源性神经营养因子表达神经元起作用。BDNFPVH的敲除减弱了瘦素对神经支配的影响。这些数据表明,瘦素信号传导通过自上而下的神经途径调节脂肪组织交感结构的可塑性,这对于能量稳态至关重要。

研究人员表示,ob的突变会导致包括严重肥胖,热生成和脂肪分解的代谢紊乱,这两者都是交感神经系统调节的脂肪组织功能。但是,这些与交感神经有关的异常的基础尚不清楚。此外,长期施用瘦蛋白可逆转脂肪组织中的这些异常,但其潜在机制尚待发现。

附:英文原文

Title: A leptin–BDNF pathway regulating sympathetic innervation of adipose tissue

Author: Putianqi Wang, Ken H. Loh, Michelle Wu, Donald A. Morgan, Marc Schneeberger, Xiaofei Yu, Jingyi Chi, Christin Kosse, Damian Kim, Kamal Rahmouni, Paul Cohen, Jeffrey Friedman

Issue&Volume: 2020-07-22

Abstract: Mutations in the leptin gene (ob) result in a metabolic disorder that includes severe obesity1, and defects in thermogenesis2 and lipolysis3, both of which are adipose tissue functions regulated by the sympathetic nervous system. However, the basis of these sympathetic-associated abnormalities remains unclear. Furthermore, chronic leptin administration reverses these abnormalities in adipose tissue, but the underlying mechanism remains to be discovered. Here we report that ob/ob mice, as well as leptin-resistant diet-induced obese mice, show significant reductions of sympathetic innervation of subcutaneous white and brown adipose tissue. Chronic leptin treatment of ob/ob mice restores adipose tissue sympathetic innervation, which in turn is necessary to correct the associated functional defects. The effects of leptin on innervation are mediated via agouti-related peptide and pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus. Deletion of the gene encoding the leptin receptor in either population leads to reduced innervation in fat. These agouti-related peptide and pro-opiomelanocortin neurons act via brain-derived neurotropic factor-expressing neurons in the paraventricular nucleus of the hypothalamus (BDNFPVH). Deletion of BDNFPVH blunts the effects of leptin on innervation. These data show that leptin signalling regulates the plasticity of sympathetic architecture of adipose tissue via a top-down neural pathway that is crucial for energy homeostasis.

DOI: 10.1038/s41586-020-2527-y

Source: https://www.nature.com/articles/s41586-020-2527-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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