导致肥胖的单基因研究进展

doi:10.3870/j.issn.1672-8009.2026.05.013

医学分子生物学杂志 ›› 2026, Vol. 23 ›› Issue (5): 577-586.doi: 10.3870/j.issn.1672-8009.2026.05.013

导致肥胖的单基因研究进展

冯钟徽^1#, 黎友琴^2#, 冯政民^3#, 邓丽³, 吕凤如³, 李尔干⁴, 廖海³, 文君⁵, 刘雁军¹

成都市第三人民医院 ¹肥胖与代谢医工结合实验室, ⁵肝胆胰外科成都市, 610000;
西南交通大学 ²医学院, ³生命科学与工程学院成都市, 610000;
⁴西南民族大学畜牧兽医学院成都市, 610000

收稿日期:2026-06-11 出版日期:2026-09-30 发布日期:2026-09-30
通讯作者: 刘雁军（E-mail：liuyanjun@swjtu.edu.cn）,廖海（E-mail：ddliaohai@home.swjtu.edu.cn）,文君（E-mail：junwen369@163.com）
作者简介:#:共同第一作者
基金资助:
国家自然科学基金（No. 82202007）,成都市第三人民医院临床研究项目（No. 2023PI22、No. CSY-YN-01-2023-039）,四川省自然科学基金（No. 2023NSFSC0739）

Research Progress on Single Genes Associated with Obesity

FENG Zhonghui^1#, LI Youqin^2#, FENG Zhengmin^3#, DENG Li³, LV Fengru³, LI Ergan⁴, LIAO Hai³, WEN Jun⁵, LIU Yanjun¹

¹Obesity and Metabolic Medicine-Engineering Joint Laboratory, ⁵Department of Hepatobiliary and Pancreatic Surgery, the Third People's Hospital of Chengdu, Chengdu, 610000, China;
²Medical School, ³School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 610000, China;
⁴College of Animal Science and Veterinary Medicine, Southwest University for Nationalities, Chengdu, 610000, China

Received:2026-06-11 Online:2026-09-30 Published:2026-09-30
Contact: LIU Yanjun （E-mail：liuyanjun@swjtu.edu.cn）,LIAO Hai （E-mail：ddliaohai@home.swjtu.edu.cn）,WEN Jun （Email：junwen369@163.com）
About author:#:These authors contributed equally as first author.
Supported by:
National Natural Science Foundation of China（No. 82202007）, the Third People's Hospital of Chengdu Clinical Research Program（No. 2023PI22, No. CSY-YN-01-2023-039）, the Natural Science Foundation of Sichuan Province（No. 2023NSFSC0739）.

摘要/Abstract

摘要： 单基因肥胖是由单个基因突变引起的肥胖,约占儿童和成人肥胖的2 %~10 %。自瘦素及其受体基因被鉴定以来,已发现超过85种单基因肥胖形式,绝大多数致病基因集中于下丘脑瘦素—黑皮质素信号通路,该通路是中枢调控食欲与能量平衡的核心枢纽。黑皮质素 4 受体（melanocortin 4 receptor, MC4R）突变是早发性单基因肥胖最常见病因基因,占所有单基因肥胖病例的1/4以上。近年来,随着全外显子测序和大规模队列研究的推进,TUB、ADCY3、ALMS1等新基因陆续被鉴定,极大拓展了单基因肥胖的遗传谱系。在临床治疗方面,基于遗传机制的精准药物已取得突破性进展：MC4R激动剂Setmelanotide已获批用于POMC、PCSK1、LEPR缺乏症及巴德-毕德氏综合征等特定遗传亚型,口服MC4R校正剂CGX-926已进入Ⅰ期临床试验。文章系统综述单基因肥胖的致病基因谱系、分子机制、遗传检测策略及靶向治疗进展,旨在为临床精准诊疗提供理论依据。

关键词: 单基因肥胖, 瘦素-黑皮质素通路, 黑皮质素 4 受体, 遗传检测, 靶向治疗

Abstract: Monogenic obesity is obesity caused by a mutation in a single gene, accounting for about 2% to 10% of obesity in children and adults. Since the identification of the leptin gene and its receptor, over 85 forms of monogenic obesity have been discovered, with the vast majority of pathogenic genes concentrated in the hypothalamic leptin-melanocortin signaling pathway, which is a key hub in the central regulation of appetite and energy balance. Mutations in the MC4R gene are the most common cause of monogenic obesity, accounting for more than a quarter of all cases. In recent years, with the advancement of whole-exome sequencing and large-scale cohort studies, new genes such as TUB, ADCY3, and ALMS1 have been identified, greatly expanding the genetic spectrum of monogenic obesity. In terms of clinical treatment, precision drugs based on genetic mechanisms have made breakthrough progress： the MC4R agonist setmelanotide has been approved for specific genetic subtypes such as POMC, PCSK1, LEPR deficiencies, and Bardet-Biedl syndrome, while the oral MC4R modulator CGX-926 has entered Phase I clinical trials. This article provides a systematic overview of the pathogenic gene spectrum, molecular mechanisms, genetic testing strategies, and targeted treatment progress in monogenic obesity, aiming to provide a theoretical basis for precise clinical diagnosis and treatment.

Key words: monogenic obesity, leptin-melanocortin pathway, melanocortin 4 receptor, genetic testing, targeted therapy

中图分类号:

R589
Q255

冯钟徽, 黎友琴, 冯政民, 邓丽, 吕凤如, 李尔干, 廖海, 文君, 刘雁军. 导致肥胖的单基因研究进展[J]. 医学分子生物学杂志, 2026, 23(5): 577-586.

FENG Zhonghui, LI Youqin, FENG Zhengmin, DENG Li, LV Fengru, LI Ergan, LIAO Hai, WEN Jun, LIU Yanjun. Research Progress on Single Genes Associated with Obesity[J]. Journal of Medical Molecular Biology, 2026, 23(5): 577-586.

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导致肥胖的单基因研究进展

Research Progress on Single Genes Associated with Obesity

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