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纤毛:一种影响肥胖风险的细胞天线。

The cilium: a cellular antenna with an influence on obesity risk.

作者信息

Mariman Edwin C M, Vink Roel G, Roumans Nadia J T, Bouwman Freek G, Stumpel Constance T R M, Aller Erik E J G, van Baak Marleen A, Wang Ping

机构信息

1Department of Human Biology,School of Nutrition and Translational Research in Metabolism (NUTRIM),Maastricht University Medical Centre,PO Box 616, 6200 MD Maastricht,The Netherlands.

2Department of Clinical Genetics,Maastricht University Medical Centre,PO Box 5800, 6202 AZ Maastricht,The Netherlands.

出版信息

Br J Nutr. 2016 Aug;116(4):576-92. doi: 10.1017/S0007114516002282. Epub 2016 Jun 20.

Abstract

Primary cilia are organelles that are present on many different cell types, either transiently or permanently. They play a crucial role in receiving signals from the environment and passing these signals to other parts of the cell. In that way, they are involved in diverse processes such as adipocyte differentiation and olfactory sensation. Mutations in genes coding for ciliary proteins often have pleiotropic effects and lead to clinical conditions, ciliopathies, with multiple symptoms. In this study, we reviewed observations from ciliopathies with obesity as one of the symptoms. It shows that variation in cilia-related genes is itself not a major cause of obesity in the population but may be a part of the multifactorial aetiology of this complex condition. Both common polymorphisms and rare deleterious variants may contribute to the obesity risk. Genotype-phenotype relationships have been noticed. Among the ciliary genes, obesity differs with regard to severity and age of onset, which may relate to the influence of each gene on the balance between pro- and anti-adipogenic processes. Analysis of the function and location of the proteins encoded by these ciliary genes suggests that obesity is more linked to activities at the basal area of the cilium, including initiation of the intraflagellar transport, but less to the intraflagellar transport itself. Regarding the role of cilia, three possible mechanistic processes underlying obesity are described: adipogenesis, neuronal food intake regulation and food odour perception.

摘要

原发性纤毛是存在于许多不同细胞类型上的细胞器,要么是短暂存在,要么是永久存在。它们在接收来自环境的信号并将这些信号传递到细胞的其他部分方面发挥着关键作用。通过这种方式,它们参与了多种过程,如脂肪细胞分化和嗅觉。编码纤毛蛋白的基因突变通常具有多效性,并导致临床病症,即纤毛病,伴有多种症状。在本研究中,我们回顾了以肥胖为症状之一的纤毛病的观察结果。结果表明,纤毛相关基因的变异本身并非人群中肥胖的主要原因,但可能是这种复杂病症多因素病因的一部分。常见的多态性和罕见的有害变异都可能导致肥胖风险。已经注意到基因型与表型的关系。在纤毛基因中,肥胖在严重程度和发病年龄方面存在差异,这可能与每个基因对促脂肪生成和抗脂肪生成过程平衡的影响有关。对这些纤毛基因编码的蛋白质的功能和位置进行分析表明,肥胖与纤毛基部区域的活动联系更紧密,包括鞭毛内运输的起始,但与鞭毛内运输本身的联系较少。关于纤毛的作用,描述了肥胖潜在的三种可能机制过程:脂肪生成、神经元食物摄入调节和食物气味感知。

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