遗传和表观遗传 GNAS 改变在早发性肥胖症发病过程中的作用

IF 6.4 2区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Mutation Research-Reviews in Mutation Research Pub Date : 2023-12-14 DOI:10.1016/j.mrrev.2023.108487
Alaa Abbas , Ayat S Hammad , Mashael Al-Shafai
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引用次数: 0

摘要

背景GNAS(鸟嘌呤核苷酸结合蛋白,α刺激性)是一种印迹基因,编码异三聚刺激性G蛋白的α亚基Gsα。该亚基介导多种 G 蛋白偶联受体(GPCR)的信号传导,其中包括在调节食物摄入量、能量平衡和体重方面发挥关键作用的黑皮质素 4 受体(MC4R)。已知 GNAS 的遗传或表观遗传改变可导致不同亚型的假性甲状旁腺功能亢进症,最近还发现它与孤立的、早发的重度肥胖有关。鉴于 Gsα 具有多种生物学功能,涉及 MC4R、β2- 和 β3-肾上腺素受体以及促肾上腺皮质激素释放激素受体等各种 GPCR 的多种分子机制已被认为与遗传或表观遗传 GNAS 变化导致的早发性重度肥胖的病理生理学有关。此外,它还阐明了 Gsα 缺乏症诱发早发性肥胖症的潜在分子机制,强调了这些机制对诊断、管理和治疗这种复杂疾病的一些影响。主要结论Gsα 缺乏症是早发性重度肥胖症的一个未被重视的病因。因此,建议对不明原因的重度肥胖症患儿进行 GNAS 缺陷筛查,以加强对这种疾病的分子诊断和管理。
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The role of genetic and epigenetic GNAS alterations in the development of early-onset obesity

Background

GNAS (guanine nucleotide-binding protein, alpha stimulating) is an imprinted gene that encodes Gsα, the α subunit of the heterotrimeric stimulatory G protein. This subunit mediates the signalling of a diverse array of G protein-coupled receptors (GPCRs), including the melanocortin 4 receptor (MC4R) that serves a pivotal role in regulating food intake, energy homoeostasis, and body weight. Genetic or epigenetic alterations in GNAS are known to cause pseudohypoparathyroidism in its different subtypes and have been recently associated with isolated, early-onset, severe obesity. Given the diverse biological functions that Gsα serves, multiple molecular mechanisms involving various GPCRs, such as MC4R, β2- and β3-adrenoceptors, and corticotropin-releasing hormone receptor, have been implicated in the pathophysiology of severe, early-onset obesity that results from genetic or epigenetic GNAS changes.

Scope of review

This review examines the structure and function of GNAS and provides an overview of the disorders that are caused by defects in this gene and may feature early-onset obesity. Moreover, it elucidates the potential molecular mechanisms underlying Gsα deficiency-induced early-onset obesity, highlighting some of their implications for the diagnosis, management, and treatment of this complex condition.

Major conclusions

Gsα deficiency is an underappreciated cause of early-onset, severe obesity. Therefore, screening children with unexplained, severe obesity for GNAS defects is recommended, to enhance the molecular diagnosis and management of this condition.

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来源期刊
CiteScore
12.20
自引率
1.90%
发文量
22
审稿时长
15.7 weeks
期刊介绍: The subject areas of Reviews in Mutation Research encompass the entire spectrum of the science of mutation research and its applications, with particular emphasis on the relationship between mutation and disease. Thus this section will cover advances in human genome research (including evolving technologies for mutation detection and functional genomics) with applications in clinical genetics, gene therapy and health risk assessment for environmental agents of concern.
期刊最新文献
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