From leptin to lasers: the past and present of mouse models of obesity

Introduction: Obesity is a prevalent condition that accounts for significant morbidity and mortality across the globe. Despite substantial effort, most obesity pharmacotherapies have proven unsafe or ineffective. The use of obese mouse models provides unique insight into the hormones and mechanisms that regulate appetite and metabolism. Paramount among these models are the 'obese' and 'diabetic' mice that revealed the powerful satiety hormone leptin, revolutionizing obesity research. Areas Covered: In this article, the authors discuss work on leptin therapy, and the clinical response to leptin in humans. The authors describe the use of modern mouse genetics to study targetable mechanisms for genetic forms of human obesity. Additionally, they describe mouse models of neuromodulation and their utility in unraveling neural circuits that govern appetite and metabolism. Expert opinion: Combining past and present models of obesity is required for the development of safe, effective, and impactful obesity therapy. Current research in obesity can benefit from repositories of genetically engineered mouse models to discover interactions between appetitive systems and circuits. Combining leptin therapy with other satiety signals comprising the gut-brain axis is a promising approach to induce significant enduring weight loss.

Automated summary

The use of obese mouse models, especially the 'obese' and 'diabetic' mice, has revolutionized obesity research by revealing the powerful satiety hormone leptin. Research on leptin therapy and its clinical response in humans, as well as the study of targetable mechanisms for genetic forms of human obesity using modern mouse genetics, are discussed in this article. Additionally, mouse models of neuromodulation are described for unraveling neural circuits that govern appetite and metabolism, presenting new opportunities for the development of safe and effective obesity therapy.