Henry Belinda A
Metabolic Disease and Obesity Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Clayton, VIC, Australia.
Neuroendocrinology. 2017;104(4):319-329. doi: 10.1159/000455232. Epub 2016 Dec 24.
The incidence of obesity is rapidly escalating and has reached epidemic proportions. In all species, including rodents, humans, and sheep, there is large variation in the degree of weight gain across individuals in response to an obesogenic environment. This individual variation is, at least in part, determined by innate differences in energy expenditure, of which adaptive thermogenesis is a key component. The hypothalamus is essential to the control of body weight and adiposity. Appetite-regulating peptides within the hypothalamus exert reciprocal effects on food intake and energy expenditure, such that neuropeptides that stimulate food intake inhibit thermogenesis and vice versa. This review discusses the role of the hypothalamic neuropeptides in determining innate predisposition to obesity in 3 animal models being obesity-prone and obesity-resistant rodents, genetically lean and obese sheep, and animals selected for high/low cortisol responsiveness. In rodents, leptin resistance is a primary feature of the propensity to become obese. This contrasts that of larger mammals, such as sheep, where altered susceptibility to obesity manifests within the melanocortin and/or orexin pathways. This review highlights fundamental species differences within the hypothalamus that lead to altered susceptibility to weight gain and increased propensity to become obese.
肥胖的发病率正在迅速上升，已达到流行程度。在所有物种中，包括啮齿动物、人类和绵羊，面对致胖环境时，个体间体重增加的程度存在很大差异。这种个体差异至少部分是由能量消耗的先天差异决定的，其中适应性产热是一个关键组成部分。下丘脑对于体重和肥胖的控制至关重要。下丘脑内调节食欲的肽对食物摄入和能量消耗产生相互作用，即刺激食物摄入的神经肽会抑制产热，反之亦然。本综述讨论了下丘脑神经肽在三种动物模型中决定肥胖先天易感性的作用，这三种动物模型分别是易肥胖和抗肥胖的啮齿动物、基因瘦型和肥胖型绵羊，以及选择用于高/低皮质醇反应性的动物。在啮齿动物中，瘦素抵抗是易肥胖倾向的一个主要特征。这与较大的哺乳动物如绵羊形成对比，在绵羊中，肥胖易感性的改变表现在黑皮质素和/或食欲素途径中。本综述强调了下丘脑内导致体重增加易感性改变和肥胖倾向增加的基本物种差异。
