Central and peripheral regulation of food intake and physical activity: pathways and genes.
Central and peripheral regulation of food intake and physical activity: pathways and genes.
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DOI：
10.1038/oby.2008.511
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发表时间：
2008-12
期刊：
影响因子：
6.9
通讯作者：
Berthoud, Hans-Rudolf
中科院分区：
文献类型：
--
作者：
Lenard, Natalie R.;Berthoud, Hans-Rudolf
环境和生活方式的变化是对当前肥胖流行的最重要的解释。然而，现代环境推翻食欲和动态平衡体重调节的生理控制的机制尚不清楚。食物摄入量和能量消耗由复杂的、冗余的和分布式的神经系统控制，涉及数千个基因，反映了充足的营养供应和能量平衡的基本生物学重要性。在确定下丘脑和尾侧脑干在各种激素和神经机制中的重要作用方面已经取得了很大进展，大脑通过这些机制告知自己摄入和储存的营养物质的可用性，进而产生行为、自主和内分泌输出。在众所周知的单基因肥胖模型中，这种“内环境平衡”调节因子所涉及的一些基因对能量平衡至关重要。然而，可以清楚地证明，动物和人类神经系统的更大部分，包括皮质、基底节和边缘系统，与食物的获取有关，作为一种基本的和进化上保守的生存机制，以捍卫肥胖的下限。通过学习和记忆的过程形成表征和奖励期望，这些系统进化成参与强大的情感，以保证从稀疏和通常是敌对的环境中供应和摄取有益的食物。它们现在只是被大量的食物和食物线索淹没了，不再受到捕食者的竞争，也不再被饥荒打断。这些复杂的神经系统的解剖、化学和功能，以及它们与下丘脑中的“内稳态”调节因子的相互作用，人们知之甚少，涉及的许多基因要么未知，要么没有很好的特征。这是令人遗憾的，因为这些系统直接并主要涉及现代环境和生活方式与人体的相互作用。它们的“生理性”不亚于在过去15年里吸引了大部分研究的新陈代谢调节机制。
A changing environment and lifestyle on the background of evolutionary engraved and perinatally imprinted physiological response patterns is the foremost explanation for the current obesity epidemic. However, it is not clear what the mechanisms are by which the modern environment overrides the physiological controls of appetite and homeostatic body-weight regulation. Food intake and energy expenditure are controlled by complex, redundant, and distributed neural systems involving thousands of genes and reflecting the fundamental biological importance of adequate nutrient supply and energy balance. There has been much progress in identifying the important role of hypothalamus and caudal brainstem in the various hormonal and neural mechanisms by which the brain informs itself about availability of ingested and stored nutrients and, in turn, generates behavioral, autonomic, and endocrine output. Some of the genes involved in this “homeostatic” regulator are crucial for energy balance as manifested in the well-known monogenic obesity models. However, it can be clearly demonstrated that much larger portions of the nervous system of animals and humans, including the cortex, basal ganglia, and the limbic system, are concerned with the procurement of food as a basic and evolutionarily conserved survival mechanism to defend the lower limits of adiposity. By forming representations and reward expectancies through processes of learning and memory, these systems evolved to engage powerful emotions for guaranteed supply with, and ingestion of, beneficial foods from a sparse and often hostile environment. They are now simply overwhelmed with an abundance of food and food cues no longer contested by predators and interrupted by famines. The anatomy, chemistry, and functions of these elaborate neural systems and their interactions with the “homeostatic” regulator in the hypothalamus are poorly understood, and many of the genes involved are either unknown or not well characterized. This is regrettable because these systems are directly and primarily involved in the interactions of the modern environment and lifestyle with the human body. They are no less “physiological” than metabolic-regulatory mechanisms that have attracted most of the research during the past 15 years.
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