最新研究发现食欲调控与体内自由基有关。由胃分泌的激素Ghrelin，通过调控下丘脑弓状核中的NPY/AgRP神经元来刺激食物吸收。它是怎样做到这一点的过去并不清楚，但现在用小鼠所做研究表明，由Ghrelin诱导的食欲增强是由在下丘脑线粒体中燃烧脂肪驱动的，该线粒体能产生被线粒体蛋白UCP2（去耦合蛋白2）利用的自由基。这便提出一个可能性：自由基参与了食欲调控，能够影响自由基的干涉也许能够影响食欲及吃饱的感觉。此项研究结果发表在新一期的Nature上面。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 454, 846-851 (14 August 2008) | doi:10.1038/nature07181
UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals
Zane B. Andrews1,2, Zhong-Wu Liu2,5, Nicholas Walllingford2, Derek M. Erion2, Erzsebet Borok2, Jeffery M. Friedman6, Matthias H. Tschöp7, Marya Shanabrough2, Gary Cline3, Gerald I. Shulman3, Anna Coppola2, Xiao-Bing Gao2, Tamas L. Horvath1,2,4 & Sabrina Diano2,4
Section of Comparative Medicine and Departments of,
Obstetrics, Gynecology & Reproductive Sciences
Internal Medicine, Howard Hughes Medical Institute and,
Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Department of Neurobiology, Yunyang Medical College, Shiyan, Hubei 442000, China
Laboratory of Molecular Genetics, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA
Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio 45237, USA
Correspondence to: Tamas L. Horvath1,2,4Sabrina Diano2,4 Correspondence and requests for materials should be addressed to T.L.H. (Email: tamas.horvath@yale.edu) or S.D. (Email: sabrina.diano@yale.edu).
Abstract
The gut-derived hormone ghrelin exerts its effect on the brain by regulating neuronal activity. Ghrelin-induced feeding behaviour is controlled by arcuate nucleus neurons that co-express neuropeptide Y and agouti-related protein (NPY/AgRP neurons). However, the intracellular mechanisms triggered by ghrelin to alter NPY/AgRP neuronal activity are poorly understood. Here we show that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake. The UCP2-dependent action of ghrelin on NPY/AgRP neurons is driven by a hypothalamic fatty acid oxidation pathway involving AMPK, CPT1 and free radicals that are scavenged by UCP2. These results reveal a signalling modality connecting mitochondria-mediated effects of G-protein-coupled receptors on neuronal function and associated behaviour.
