Long-term management of body weight and physiological mechanisms of weight regain

Overweight and obesity are major global health challenges. Despite progress in behavioral interventions, nutrition, physical activity, pharmacotherapy, and bariatric procedures, weight regain (WR) after successful weight loss is a major challenge. Understanding the definition and physiological mechanisms of WR is crucial for developing effective strategies to tackle weight regain and reduce cardiometabolic disorders. This review summarizes recent advances in weight loss strategies. We also discuss the metrics used to quantify WR, emphasizing the need for standardization to facilitate comparison between studies, and examine WR predictors including demographic and clinical characteristics, behavior, anatomic factors, and biological markers. The potential physiological mechanisms underlying WR, focusing on obesity memory, metabolic adaptation, and gut hormone alterations are further elucidated. Comprehensively understanding WR provides a foundation for developing long-term, personalized strategies and integrating emerging technologies such as artificial intelligence into long-term weight management.