The genetic blueprint of obesity : from pathogenesis to novel therapies

Tonin, Gašper (author), Eržen, Stjepan (author), Mlinarič, Zala (author), Jurišić-Eržen, Dubravka (author), Horvat, Simon (author), Kunej, Tanja (author), Klen, Jasna (author)

Obesity is a chronic metabolic disease characterized by disturbances in energy homeostasis, leading to excessive fat accumulation. The pathogenesis of the disease is shaped by a complex interplay of genetic, epigenetic, biological, psychological, and environmental factors. These contributors affect regulatory mechanisms in the hypothalamus, hormonal signaling, and the gut-brain axis, all of which control energy intake, expenditure, and energy utilization in body tissues. In this context, particular attention is given to the role of genetic factors, which have a major impact on an individual's susceptibility to disease and support the development of personalized preventive and therapeutic approaches. Modern obesity treatment goes beyond weight reduction and focuses on optimizing body composition by reducing fat mass and increasing lean mass. This review includes a detailed overview of the mechanisms and clinical effects of current pharmacological approaches to obesity treatment, alongside other established strategies such as lifestyle modifications and bariatric surgery. It specifically discusses lipase inhibitors, opioid antagonists, sympathomimetics, and GLP-1 receptor agonists. Looking ahead, emerging therapies—such as microbiota modulation, dual and triple drug combinations, PYY agonists, and monoclonal antibodies—are expected to play a crucial role in the management of obesity. Furthermore, this review explores the potential of CRISPR-based technology for monogenic obesity, opening new avenues for targeted obesity treatments and identifying promising research directions. In the time to come, personalized medicine might have a fundamental place in the management of obesity, providing tailored and more effective therapeutic approaches that prioritize the long-term improvement of body composition and health outcomes in patients.

• Language: English
• Keywords: CRISPR/Cas9, dual therapy, energy homeostasis, gene therapy, gut–brain axis, microbiota, personalized medicine
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 38 str.
• Numbering: Vol. 26, iss. 12, art. e13978
• PID: 20.500.12556/RUL-176190
• UDC: 575
• ISSN on article: 1467-789X
• DOI: 10.1111/obr.13978
• COBISS.SI-ID: 242378243
• Publication date in RUL: 24.11.2025

Record is a part of a journal

• Title: Obesity reviews
• Shortened title: Obes. rev.
• Publisher: Wiley, World Obesity Federation
• ISSN: 1467-789X
• COBISS.SI-ID: 517799449

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

Secondary language

• Language: Slovenian
• Keywords: genetika, debelost, patogeneza, terapije

Projects

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: P4-0220
• Name: Primerjalna genomika in genomska biodiverziteta

• Funder: ARIS - Slovenian Research and Innovation Agency
• Project number: J7-60131
• Name: Integracija epigenomike in prostorske transkriptomike pri poligenem živalskem modelu za debelost