20.500.12556/RUL-176190 The genetic blueprint of obesity from pathogenesis to novel therapies 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. CRISPR/Cas9 dual therapy energy homeostasis gene therapy gut–brain axis microbiota personalized medicine genetika debelost patogeneza terapije true false true Angleški jezik Slovenski jezik Članek v reviji 2025-11-24 14:57:30 2025-11-24 14:57:31 2026-01-07 04:28:46 0000-00-00 00:00:00 2025 0 0 38 str. iss. 12, art. e13978 Vol. 26 Dec. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 575 1467-789X 10.1111/obr.13978 242378243 RAZ_Tonin_Gasper_2025.pdf RAZ_Tonin_Gasper_2025.pdf 1 39469F178919DD63FE88A666F2112015 2af28c11d6841d4534db90aa6a0eac103c543ed4bf2cdeb4d59fe03943fe5e96 53fc9aab-ead5-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225013 https://onlinelibrary.wiley.com/doi/10.1111/obr.13978 0 68644ea0-ead5-11f0-bf92-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=225014 Medicinska fakulteta Biotehniška fakulteta 0 0 0