Genetic variation in satiety signaling and hypothalamic inflammation: merging fields for the study of obesity.
Genetic variation in satiety signaling and hypothalamic inflammation: merging fields for the study of obesity.
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DOI：
10.1016/j.jnutbio.2021.108928
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Solberg Woods LC
中科院分区：
文献类型：
--
作者：
Szalanczy AM;Key CC;Solberg Woods LC
虽然肥胖一直是一个长期的健康危机，但对这种疾病的遗传结构仍然知之甚少。全基因组关联研究已经确定了许多与肥胖相关的基因组位点，其中基因在大脑中富集，特别是在下丘脑中。这表明了中枢神经系统（CNS）在肥胖易感性中的作用，我们在这里强调了与遗传易感性相关的饱腹感信号通路沿着的几个关键基因。人们对慢性、低度肥胖相关炎症的兴趣也在增加，人们越来越关注下丘脑炎症是肥胖的前兆。最近的研究发现，炎症基因的遗传变异在肥胖易感性中起作用，我们在这里强调几个关键基因。尽管对这些途径的遗传变异很感兴趣，但缺乏调查两者之间关系的研究。了解CNS中富集的肥胖基因和炎症基因的遗传变异之间的相互作用将促进我们对肥胖病因学和异质性的理解，改善遗传风险预测分析，并突出治疗肥胖的新药靶点。此外，这种知识的增加将有助于医生制定个性化的营养和药物策略，以对抗肥胖症的流行。尽管肥胖症似乎经常普遍存在，但它是一种高度个体化的疾病，并且在该领域中仍然需要开发在个体水平上治疗的方法。
Although obesity has been a longstanding health crisis, the genetic architecture of the disease remains poorly understood. Genome-wide association studies have identified many genomic loci associated with obesity, with genes being enriched in the brain, particularly in the hypothalamus. This points to the role of the central nervous system (CNS) in predisposition to obesity, and we emphasize here several key genes along the satiety signaling pathway involved in genetic susceptibility. Interest has also risen regarding the chronic, low-grade obesity-associated inflammation, with a growing concern towards inflammation in the hypothalamus as a precursor to obesity. Recent studies have found that genetic variation in inflammatory genes play a role in obesity susceptibility, and we highlight here several key genes. Despite the interest in the genetic variants of these pathways individually, there is a lack of research that investigates the relationship between the two. Understanding the interplay between genetic variation in obesity genes enriched in the CNS and inflammation genes will advance our understanding of obesity etiology and heterogeneity, improve genetic risk prediction analyses, and highlight new drug targets for the treatment of obesity. Additionally, this increased knowledge will assist in physician’s ability to develop personalized nutrition and medication strategies for combating the obesity epidemic. Though it often seems to present universally, obesity is a highly individual disease, and there remains a need in the field to develop methods to treat at the individual level.
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