SMIM1 的缺失与能量消耗减少和体重超标有关。

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Med Pub Date : 2024-09-13 Epub Date: 2024-06-20 DOI:10.1016/j.medj.2024.05.015
Luca Stefanucci, Camous Moslemi, Ana R Tomé, Samuel Virtue, Guillaume Bidault, Nicholas S Gleadall, Laura P E Watson, Jing E Kwa, Frances Burden, Samantha Farrow, Ji Chen, Urmo Võsa, Keith Burling, Lindsay Walker, John Ord, Peter Barker, James Warner, Amy Frary, Karola Renhstrom, Sofie E Ashford, Jo Piper, Gail Biggs, Wendy N Erber, Gary J Hoffman, Nadia Schoenmakers, Christian Erikstrup, Klaus Rieneck, Morten H Dziegiel, Henrik Ullum, Vian Azzu, Michele Vacca, Hugo Javier Aparicio, Qin Hui, Kelly Cho, Yan V Sun, Peter W Wilson, Omer A Bayraktar, Antonio Vidal-Puig, Sisse R Ostrowski, William J Astle, Martin L Olsson, Jill R Storry, Ole B Pedersen, Willem H Ouwehand, Krishna Chatterjee, Dragana Vuckovic, Mattia Frontini
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引用次数: 0

摘要

背景:在过去 50 年中,肥胖率几乎增加了两倍,预计到 2030 年,全球将有超过 10 亿人肥胖。由于相关的非传染性疾病,这造成了巨大的经济压力。肥胖的根本原因是生活方式、环境和遗传因素相互作用导致的能量消耗失衡。肥胖具有多基因遗传结构;然而,在少数病例中,具有较大效应的单基因变异是病因。通过这些变异发现了与体重调节相关的新型基因和生物学特性,并最终开发出了新型特效疗法:方法:我们利用五个队列的数据,采用病例对照的方法来确定小整体膜蛋白 1(SMIM1)功能缺失遗传变异的同卵个体与普通人群之间的代谢差异。利用血浆生化、热量测定室和 DXA 扫描对 SMIM1-/- 个体进行了代谢特征描述:我们发现,血型 Vel 的基础基因 SMIM1 基因中的功能缺失遗传变异的同卵双生个体表现出超重、血脂异常、瘦素与脂肪连通素比率改变、肝酶升高和甲状腺激素水平降低。结论:这项研究发现了一种新的遗传易感性:这项研究发现了一种新的超重或肥胖遗传倾向。结论:这项研究发现了一种新的超重或肥胖遗传易感性,强调了研究肥胖遗传原因的必要性,以选择最合适的治疗方法,因为它们之间存在巨大的成本差异:本研究由英国国家健康研究所、英国心脏基金会和英国国家医疗服务系统血液与移植处资助。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
SMIM1 absence is associated with reduced energy expenditure and excess weight.

Background: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments.

Methods: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan.

Findings: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure.

Conclusion: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them.

Funding: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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