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脂肪组织、肠道、胰腺和大脑之间关于控制体重的对话。

A talk between fat tissue, gut, pancreas and brain to control body weight.

作者信息

Wilson Jenny L, Enriori Pablo J

机构信息

Department of Physiology, Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria 3800, Australia.

Department of Physiology, Monash Obesity & Diabetes Institute, Monash University, Clayton, Victoria 3800, Australia.

出版信息

Mol Cell Endocrinol. 2015 Dec 15;418 Pt 2:108-19. doi: 10.1016/j.mce.2015.08.022. Epub 2015 Aug 24.

Abstract

The incidence of obesity and its related disorders are increasing at a rate of pandemic proportions. Understanding the mechanisms behind the maintenance of energy balance is fundamental in developing treatments for clinical syndromes including obesity and diabetes. A neural network located in the nucleus of the solitary tract-area postrema complex in the hindbrain and the hypothalamus in the forebrain has long been implicated in the control of energy balance. In the hypothalamus this central neuronal network consists of small populations of nuclei with distinct functions such as the arcuate nucleus (ARH), the paraventricular nuclei of the hypothalamus (PVH), the dorsomedial (DMH), the ventromedial (VMH) and the lateral hypothalamus (LH). These hypothalamic areas form interconnected neuronal circuits that respond to fluctuations in energy status by altering the expression of neuropeptides, leading to changes in energy intake and expenditure. Regulation of these hypothalamic nuclei involves the actions of orexigenic peptides (ie ghrelin), which act to stimulate energy intake and decrease energy expenditure, and anorexigenic peptides (ie. leptin and insulin), which act to reduce energy intake and stimulate energy expenditure. Here we review the role of the ARH, DMH and PVH in the control of energy homeostasis and how recent advances in research technologies (Cre-loxP technology, optogenetics and pharmacogenetics) have shed light on the role of these hypothalamic nuclei in the control of energy balance. Such novel findings include the implication of ARH POMC and AgRP neurons in the browning of white adipose tissue to regulate energy expenditure as well as the likely existence of divergent hypothalamic pathways in the DMH and PVH in the control of food intake and energy expenditure.

摘要

肥胖及其相关疾病的发病率正以大流行的比例增长。了解能量平衡维持背后的机制是开发包括肥胖和糖尿病在内的临床综合征治疗方法的基础。位于后脑孤束核 - 最后区复合体和前脑下丘脑的神经网络长期以来一直被认为与能量平衡的控制有关。在下丘脑中,这个中枢神经元网络由少量具有不同功能的核组成,如弓状核(ARH)、下丘脑室旁核(PVH)、背内侧核(DMH)、腹内侧核(VMH)和外侧下丘脑(LH)。这些下丘脑区域形成相互连接的神经元回路,通过改变神经肽的表达来响应能量状态的波动,从而导致能量摄入和消耗的变化。对这些下丘脑核的调节涉及促食欲肽(即胃饥饿素)的作用,其作用是刺激能量摄入并减少能量消耗,以及抑食欲肽(即瘦素和胰岛素)的作用,其作用是减少能量摄入并刺激能量消耗。在这里,我们综述了ARH、DMH和PVH在能量稳态控制中的作用,以及研究技术(Cre-loxP技术、光遗传学和药物遗传学)的最新进展如何揭示这些下丘脑核在能量平衡控制中的作用。这些新发现包括ARH POMC和AgRP神经元在白色脂肪组织褐变以调节能量消耗中的作用,以及在DMH和PVH中可能存在不同的下丘脑途径来控制食物摄入和能量消耗。

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