Berthoud Hans-Rudolf
Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Physiol Behav. 2007 Aug 15;91(5):486-98. doi: 10.1016/j.physbeh.2006.12.016. Epub 2007 Jan 12.
If the new environment and modern lifestyle cause obesity in individuals with thrifty genes by increasing energy intake, it is important to know by what mechanisms hyperphagia occurs and why energy balance is not kept in check by the homeostatic regulator. The argument is developed that procuring and ingesting food is an evolutionarily conserved survival mechanism that occupies large parts of the brain's computing capacity including not only the hypothalamus but also a number of cortico-limbic structures. These forebrain systems evolved to engage powerful emotions for guaranteed supply 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 that is no longer interrupted by frequent famines. After briefly reviewing structure and functions of the relevant cortico-limbic structures and the better-known hypothalamic homeostatic regulator, the review focuses mainly on interactions between the two systems. Although several cortico-limbic processes are sensitive to metabolic depletion and repletion signals, it appears that they are underlying the same reversible leptin resistance that renders hypothalamic circuits insensible to continuously high leptin levels during periods of feast. It is hypothesized that this naturally occurring leptin resistance allowed temporary neutralization of satiety mechanisms and evolved as a response to survive subsequent periods of famine. With today's continuous and abundant food availability for a segment of the population, the powerful cognitive processes to eat and the resulting overweight can partially escape negative feedback control in prone individuals most strongly expressing such thrifty genes.
如果新环境和现代生活方式通过增加能量摄入，导致具有节俭基因的个体肥胖，那么了解多食发生的机制以及为什么能量平衡没有被体内平衡调节机制控制就很重要。有一种观点认为，获取和摄取食物是一种进化上保守的生存机制，它占据了大脑很大一部分计算能力，不仅包括下丘脑，还包括一些皮质-边缘结构。这些前脑系统进化出来是为了在稀少且往往充满敌意的环境中，激发强烈的情感以确保有益食物的供应和摄取。现在，它们只是被大量的食物和食物线索淹没，而这些不再被频繁的饥荒打断。在简要回顾了相关皮质-边缘结构和更为人熟知的下丘脑体内平衡调节机制的结构与功能后，本文主要关注这两个系统之间的相互作用。尽管一些皮质-边缘过程对代谢消耗和补充信号敏感，但似乎它们是导致相同的可逆性瘦素抵抗的基础，这种抵抗使得下丘脑回路在盛宴期间对持续高水平的瘦素不敏感。据推测，这种自然发生的瘦素抵抗允许饱腹感机制暂时失效，并作为对随后饥荒时期生存的一种反应而进化。对于一部分人群来说，由于当今食物持续充足，强大的进食认知过程以及由此导致的超重，在最强烈表达此类节俭基因的易感个体中，可能会部分逃避负反馈控制。
