University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
Nat Neurosci. 2012 Oct;15(10):1343-9. doi: 10.1038/nn.3211. Epub 2012 Sep 25.
Over the past 20 years, genetic studies have illuminated critical pathways in the hypothalamus and brainstem mediating energy homeostasis, such as the melanocortin, leptin, 5-hydroxytryptamine and brain-derived neurotrophic factor signaling axes. The identification of these pathways necessary for appropriate appetitive responses to energy state has yielded insight into normal homeostatic processes. Although monogenic alterations in each of these axes result in severe obesity, such cases remain rare. The major burden of disease is carried by those with common obesity, which has so far resisted yielding meaningful biological insights. Recent progress into the etiology of common obesity has been made with genome-wide association studies. Such studies now reveal more than 32 different candidate obesity genes, most of which are highly expressed or known to act in the CNS, emphasizing, as in rare monogenic forms of obesity, the role of the brain in predisposition to obesity.
在过去的 20 年中，遗传研究阐明了下丘脑和脑干中介能量稳态的关键途径，如黑素细胞皮质素、瘦素、5-羟色胺和脑源性神经营养因子信号轴。这些途径对于适当的食欲反应到能量状态的识别，为正常的体内平衡过程提供了深入的了解。尽管这些轴中的每一个的单基因突变都会导致严重的肥胖，但这种情况仍然很少见。大多数疾病负担是由常见肥胖的人承担的，而常见肥胖迄今仍未能提供有意义的生物学见解。全基因组关联研究在常见肥胖的病因学方面取得了最新进展。这些研究现在揭示了超过 32 个不同的候选肥胖基因，其中大多数在中枢神经系统中高度表达或已知起作用，这强调了大脑在肥胖易感性中的作用，就像罕见的单基因肥胖形式一样。
