Research Progress on Single Genes Associated with Obesity

doi:10.3870/j.issn.1672-8009.2026.05.013

Abstract

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

CLC Number:

R589
Q255

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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