2012年9月19日 訊 /生物谷BIOON/ --近日,，來(lái)自國(guó)際雜志The EMBO Journal上的一篇研究報(bào)告揭示了，小鼠大腦中特定類(lèi)型神經(jīng)元的缺失可以導(dǎo)致其肥胖和產(chǎn)生糖尿病,，然而這種結(jié)果的產(chǎn)生依賴(lài)于被喂養(yǎng)小鼠的特定類(lèi)型的飲食方式,。
AgRP神經(jīng)元是涉及控制食物攝取的特定大腦細(xì)胞，如果小鼠以規(guī)律性的碳水化物為食,，那么缺少AgRP神經(jīng)元可以導(dǎo)致小鼠肥胖,。然而缺失AgRP神經(jīng)元的動(dòng)物可以提高高脂肪的飲食，其可以變得無(wú)脂肪而且更加健康,。這種差別是由于AgRP神經(jīng)元對(duì)機(jī)體損傷和營(yíng)養(yǎng)儲(chǔ)存組織的不同影響所致。缺少AgRP神經(jīng)元的小鼠不能適應(yīng)碳水化合物為飲食,，而且其代謝模式似乎更適合于以脂肪為食,。
對(duì)肥胖和其它代謝疾病的敏感性被認(rèn)為是由于復(fù)雜的遺傳干擾和根本環(huán)境的改變所致,，然而你每天吃什么、你的遺傳組成是什么,，這并不僅僅是一個(gè)問(wèn)題,；而且你的機(jī)體如何設(shè)法對(duì)食物進(jìn)行轉(zhuǎn)換、儲(chǔ)存以及使用食物的營(yíng)養(yǎng),，這更是一個(gè)復(fù)雜的過(guò)程,。、
本項(xiàng)研究中,，研究者揭示了,，對(duì)從出生開(kāi)始就缺失AgRP神經(jīng)元的小鼠喂食碳水化合物，往往可以使得小鼠變得過(guò)度肥胖,，而其血液中胰島素水平較高,，葡萄糖水平正常。當(dāng)相同類(lèi)型的小鼠被喂以好脂肪飲食后,，其體重會(huì)明顯下降,，而且會(huì)改善這類(lèi)小鼠血液中葡萄糖的清除率。
研究者Luquet表示,，我們的研究工作揭示了大腦中的中央回路在控制食物攝取的同時(shí),，也可以控制營(yíng)養(yǎng)物質(zhì)用于次要的機(jī)體器官。未來(lái)研究中,，AgRP神經(jīng)元或許為揭示肥胖和其相關(guān)的疾病的分子機(jī)理提供新的研究思路,。（生物谷Bioon.com）
編譯自：Brain Neurons and Diet Influence Onset of Obesity and Diabetes in Mice
doi:10.1038/emboj.2012.250
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PMID:
Hypothalamic AgRP-neurons control peripheral substrate utilization and nutrient partitioning
Aurélie Joly-Amado, Raphaël G P Denis, Julien Castel, Amélie Lacombe, Céline Cansell, Claude Rouch, Nadim Kassis, Julien Dairou, Patrice D Cani, Renée Ventura-Clapier, Alexandre Prola, Melissa Flamment, Fabienne Foufelle, Christophe Magnan and Serge Luquet
Obesity-related diseases such as diabetes and dyslipidemia result from metabolic alterations including the defective conversion, storage and utilization of nutrients, but the central mechanisms that regulate this process of nutrient partitioning remain elusive. As positive regulators of feeding behaviour, agouti-related protein (AgRP) producing neurons are indispensible for the hypothalamic integration of energy balance. Here, we demonstrate a role for AgRP-neurons in the control of nutrient partitioning. We report that ablation of AgRP-neurons leads to a change in autonomic output onto liver, muscle and pancreas affecting the relative balance between lipids and carbohydrates metabolism. As a consequence, mice lacking AgRP-neurons become obese and hyperinsulinemic on regular chow but display reduced body weight gain and paradoxical improvement in glucose tolerance on high-fat diet. These results provide a direct demonstration of a role for AgRP-neurons in the coordination of efferent organ activity and nutrient partitioning, providing a mechanistic link between obesity and obesity-related disorders.
