Core Viewpoint - The article focuses on individuals who successfully lose weight through lifestyle changes but experience weight regain, highlighting the challenges of long-term obesity management and effective strategies to prevent weight rebound [7]. Summary by Sections Weight Rebound Challenges - A systematic review and meta-analysis indicate that approximately 75% of individuals who lose an average of 14 kg through lifestyle interventions will regain weight within about 5 years [7]. - Weight rebound is not limited to those who undergo lifestyle changes; individuals who stop medication or have undergone weight loss surgery also face similar challenges [7]. Mechanisms Behind Weight Rebound - A 2022 study found that macrophages in adipose tissue produce elevated levels of lipopolysaccharide-induced cytokines, contributing to a "fat memory" that increases the risk of weight regain [9]. - A 2023 study published in *Nature Metabolism* revealed that obese individuals have a diminished brain response to nutritional stimuli, which may be a key factor in weight rebound after successful weight loss [9]. Strategies to Reduce Weight Rebound Risk 1. **Dietary Adjustments** - High-protein, low glycemic index (GI), or low glycemic load diets can help reduce the risk of weight rebound. Anti-inflammatory dietary patterns, such as increased intake of olive oil, tomatoes, leafy greens, nuts, deep-sea fish, and fruits, while reducing refined carbohydrates, fried foods, sugary drinks, red meat, and margarine, may also lower rebound probabilities [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, increases satiety, promotes fat oxidation, and protects muscle mass, all of which help maintain weight loss. Higher levels of physical activity correlate with better weight maintenance outcomes [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are recommended to prevent weight rebound, such as reducing adipose tissue mass for more stable weight control [13]. 4. **Individualized Management and Ongoing Research** - Weight rebound is influenced by multiple factors, including diet, exercise, medication, and biomedical interventions. Future research should focus on different populations to explore more effective long-term management strategies [14].

Core Viewpoint - The article focuses on individuals who successfully lose weight through lifestyle changes but experience weight regain, highlighting the challenges of long-term obesity management and effective strategies to prevent weight rebound [7][9]. Summary by Sections Weight Regain Challenges - A systematic review and meta-analysis indicate that approximately 75% of individuals who lose an average of 14 kg through lifestyle interventions will regain weight within about five years [7]. - Weight rebound is not limited to those who undergo lifestyle changes; individuals who have weight loss surgery or stop medication also face similar challenges [7]. Mechanisms Behind Weight Regain - Research shows that macrophages in adipose tissue produce elevated levels of lipopolysaccharides and inflammatory cytokines, contributing to a "fat memory" that increases the risk of weight regain [9]. - A 2023 study from Yale University found that obese individuals have a diminished brain response to nutritional stimuli, which may be a key factor in weight rebound after successful weight loss [9]. Strategies to Reduce Weight Rebound Risk 1. **Dietary Adjustments** - High-protein, low glycemic index (GI), or low glycemic load diets can help reduce the risk of weight rebound. Anti-inflammatory dietary patterns are also recommended [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, and promotes fat oxidation, which aids in maintaining weight loss [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are suggested to prevent weight regain by reducing fat tissue mass [13]. 4. **Individualized Management and Ongoing Research** - Weight rebound is influenced by multiple factors, necessitating further scientific research to explore more effective long-term management strategies tailored to different populations [14].

Core Viewpoint - The article focuses on individuals who successfully lose weight through lifestyle changes but experience weight regain, highlighting the challenges of long-term obesity management and effective strategies to prevent weight rebound [7]. Summary by Sections Weight Regain Challenges - A systematic review and meta-analysis indicate that approximately 75% of individuals who lose an average of 14 kg through lifestyle interventions will regain weight within about 5 years [7]. - Weight rebound is not limited to those who undergo lifestyle changes; individuals who stop medication or have undergone weight loss surgery also face similar challenges [7]. Mechanisms Behind Weight Regain - A 2022 study found that macrophages in adipose tissue produce elevated levels of lipopolysaccharide-induced cytokines, contributing to a "fat memory" that increases the risk of weight regain [9]. - A 2023 study published in *Nature Metabolism* revealed that obese individuals have a diminished brain response to nutritional stimuli, which may be a key factor in weight rebound after weight loss [9]. Strategies to Reduce Weight Rebound Risk 1. **Dietary Adjustments** - High-protein, low glycemic index (GI), or low glycemic load diets can help reduce the risk of weight rebound. Anti-inflammatory dietary patterns are also recommended [11]. 2. **Increased Physical Activity** - Regular exercise improves leptin sensitivity, enhances sympathetic nervous activity, reduces hunger, and promotes fat oxidation, which aids in maintaining weight loss [12]. 3. **Pharmacological and Biomedical Interventions** - In addition to diet and exercise, pharmacological treatments and other biomedical methods are suggested to prevent weight regain by reducing fat tissue mass [13]. 4. **Individualized Management and Ongoing Research** - Weight rebound is influenced by multiple factors, necessitating further scientific research to explore effective long-term management strategies tailored to different populations [14].