Neurobiology of Nutrition and Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA.
Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Obesity (Silver Spring). 2021 Apr;29 Suppl 1:S25-S30. doi: 10.1002/oby.23080.
Physiological adaptations to intentional weight loss can facilitate weight regain. This review summarizes emerging findings on hypothalamic and brainstem circuitry in the regulation of body weight and identifies promising areas for research to improve therapeutic interventions for sustainable weight loss. There is good evidence that body weight is actively regulated in a homeostatic fashion similar to other physiological parameters. However, the defended level of body weight is not fixed but rather depends on environmental conditions and genetic background in an allostatic fashion. In an environment with plenty of easily available energy-dense food and low levels of physical activity, prone individuals develop obesity. In a majority of individuals with obesity, body weight is strongly defended through counterregulatory mechanisms, such as hunger and hypometabolism, making weight loss challenging. Among the options for treatment or prevention of obesity, those directly changing the defended body weight would appear to be the most effective ones. There is strong evidence that the mediobasal hypothalamus is a master sensor of the metabolic state and an integrator of effector actions responsible for the defense of adequate body weight. However, other brain areas, such as the brainstem and limbic system, are also increasingly implicated in body weight defense mechanisms and may thus be additional targets for successful therapies.
生理性适应于有意的体重减轻会促进体重反弹。本综述总结了在调节体重的下丘脑和脑干回路方面的新发现，并确定了有希望的研究领域，以改善可持续减肥的治疗干预措施。有充分的证据表明，体重像其他生理参数一样，以一种稳态的方式被主动调节。然而，体重的防御水平不是固定的，而是以一种适应的方式取决于环境条件和遗传背景。在一个有大量容易获得的高能量食物和低水平体力活动的环境中，易患个体易患肥胖症。在大多数肥胖者中，体重通过饥饿和代谢降低等代偿机制得到强烈的防御，使得减肥变得具有挑战性。在肥胖症的治疗或预防选择中，那些直接改变防御性体重的方法似乎是最有效的。有强有力的证据表明，中脑基底部是代谢状态的主传感器，也是负责防御适当体重的效应器动作的整合器。然而，其他脑区，如脑干和边缘系统，也越来越多地涉及到体重防御机制，因此可能是成功治疗的额外靶点。
