Reducing Adiposity in a Critical Developmental Window Has Lasting Benefits in Mice
Jaclyn S Lerea1, Laurence E Ring1, Rim Hassouna1
1Institute of Human Nutrition (J.S.L., A.C.N.N.), Columbia University, New York, New York 10032; Department of Anesthesiology (L.E.R.), Columbia University, New York, New York 10032; Naomi Berrie Diabetes Center (R.H., L.M.Z.), Columbia University, New York, New York 10032; Department of Obstetrics, Gynecology, and Reproductive Sciences (K.S.-B., T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; Department of Neurobiology (T.L.H.), Yale University School of Medicine, New Haven, Connecticut 06510; and Department of Pathology and Cell Biology (L.M.Z.), Columbia University, New York, New York 10032.
Early intervention in obesity can prevent weight regain. Dieting initiated early in life leads to lasting metabolic improvements and reduced adiposity, even after overeating resumes.
Area of Science:
- Metabolic research
- Obesity research
- Mitochondrial biology
Background:
- Compensatory decrease in energy expenditure after dieting promotes weight regain in most adults.
- Early-onset obesity is linked to impaired brown adipose tissue (BAT) mitochondrial function.
- Leptin signaling in the hypothalamus plays a crucial role in regulating energy balance.
Purpose of the Study:
- To investigate if early intervention can circumvent compensatory energy expenditure decrease and weight regain.
- To explore the impact of early-onset obesity on BAT mitochondria.
- To determine if the timing of dietary intervention affects metabolic outcomes.
Main Methods:
- Utilized mice with impaired hypothalamic leptin signaling as a model for early-onset hyperphagia and obesity.
- Assessed brown adipose tissue (BAT) mitochondrial structure and function.
- Compared the effects of weight loss initiated at different ages (weaning vs. adulthood).
- Monitored energy expenditure and adiposity following dietary interventions and subsequent overeating.
Main Results:
- Early-onset obesity impaired BAT mitochondrial structure and function, which improved with weight loss at any age.
- Weight loss in adult mice led to decreased sympathetic tone, reduced BAT thermogenesis, and promoted weight regain.
- Dietary intervention initiated at weaning prevented this decrease in energy expenditure.
- Enhanced energy expenditure persisted post-intervention, leading to lasting reductions in adiposity.
Conclusions:
- There is a critical developmental window for dietary intervention to achieve stable metabolic improvements.
- Early intervention can overcome the typical compensatory mechanisms that promote weight regain.
- Targeting early-onset obesity may offer a strategy for long-term weight management and metabolic health.
