Abstract

Obesity is a multifactorial disease characterized by excessive accumulation of adipose tissue, resulting from an imbalance between energy intake and expenditure. Mouse models have emerged as invaluable tools for elucidating the complex genetic, environmental, and physiological mechanisms driving to obesity. This chapter provides an overview of the methodologies employed to establish and study obesity in mice, highlighting their relevance to human disease. We described diet-induced obesity (DIO) protocols, which replicate environmental factors contributing to weight gain. Additionally, we discussed the use of genetic models, including whole-body knockouts such as leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice, as well as conditional knockout models targeting the hypothalamus, a critical brain region for maintaining body homeostasis. Key considerations in experimental design, such as strain selection, sex differences, and the impact of housing conditions, are discussed to ensure reproducibility and translational relevance. This chapter serves as a practical guide for researchers aiming to leverage mouse models in obesity studies, fostering a better understanding of this global health challenge. © 2025