Department of Integrative Physiology and Neuroscience, Washington State University, Pullman, Washington 99164, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington 98109, Department of Pharmacology and Physiology and Department of Cell Biology and Anatomy & Psychiatry, Hotchkiss Brain Institute, University of Calgary, Alberta T2N 4N1, Canada, Department Psychology, Columbia, New York, New York 10027, and Departments of Psychiatry and Neuroscience, Montana Sinai Ichan School of Medicine, New York, New York 10029.
J Neurosci. 2013 Nov 6;33(45):17610-6. doi: 10.1523/JNEUROSCI.3452-13.2013.
Obesity is a growing public health problem. Although convenient, the notion that obesity is simply a problem of will power is increasingly antiquated. It is becoming clear that complex interactions of environment, neurohormonal systems, and transgenerational effects directly contribute to obesity. This review highlights data presented at the Society for Neuroscience Annual Meeting in San Diego, California in 2013; and although not meant as an exhaustive review of the area, this reivew will explore seemingly disparate areas of research that, when taken as a whole, illuminate the complex topography of the causes and consequences of obesity. We discuss how disruption of the biological clock, a consequence of modern society, can lead to changes in the brain and periphery that lead to obesity. We explore how obesity can actually cause pathological changes within the hypothalamus of the brain (a key regulator of food intake and metabolic homeostasis). How reward circuitry, particularly the ventral tegmental area, responds to insulin and how these effects modulate feeding and the salience of feeding cues are mechanistically described. We also investigate how nutrition may cross generational boundaries to affect the development and function of offspring, underscoring the long reach of metabolic effects. Finally, the role of the endocannabinoid system is emphasized as a critical node in the transduction of many of these effects. Together, this review should provide perspective into the neural causes and consequences of obesity, and hopefully lead to new areas of interdisciplinary research to tackle this important public health epidemic.
肥胖是一个日益严重的公共卫生问题。尽管方便，但将肥胖仅仅视为意志力问题的观点已经越来越过时。越来越明显的是，环境、神经激素系统和跨代效应的复杂相互作用直接导致了肥胖。这篇综述强调了 2013 年在加利福尼亚州圣地亚哥举行的神经科学学会年会上提出的数据；虽然这不是对该领域的详尽综述，但这篇综述将探讨看似不同的研究领域，这些领域综合起来阐明了肥胖的原因和后果的复杂情况。我们讨论了现代社会导致的生物钟紊乱如何导致大脑和外周发生变化，从而导致肥胖。我们探讨了肥胖实际上如何导致大脑下丘脑（食物摄入和代谢平衡的关键调节剂）发生病理性变化。奖励回路，特别是腹侧被盖区，如何对胰岛素产生反应，以及这些影响如何调节进食和进食线索的显著性，在机制上进行了描述。我们还研究了营养如何跨越代际界限影响后代的发育和功能，强调了代谢影响的深远范围。最后，强调了内源性大麻素系统作为许多这些效应转导的关键节点的作用。总的来说，这篇综述应该为肥胖的神经原因和后果提供一个视角，并希望为解决这一重要的公共卫生问题开辟新的跨学科研究领域。
