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A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.
Calvin C Chan1,2,3,4, Isaac T W Harley1,2,3,4,5, Paul T Pfluger6,7,8,9
1Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Nature Communications
|May 19, 2021
Summary
The B cell activating factor (BAFF) and its homolog APRIL regulate weight gain and fat tissue function. These immune factors promote fat breakdown and energy expenditure, offering new therapeutic targets for obesity.
Area of Science:
- Immunology
- Metabolism
- Endocrinology
Background:
- The role of immune mediators in weight homeostasis is not fully understood.
- Diet-induced obesity is a significant health concern with complex regulatory pathways.
Purpose of the Study:
- To investigate the role of B cell activating factor (BAFF) in regulating weight gain and adipose tissue function.
- To explore the impact of BAFF and its homolog, A proliferation-inducing ligand (APRIL), on metabolic processes.
Main Methods:
- Overexpression of BAFF in mouse models to assess effects on weight gain.
- Gene expression analysis of BAFF-stimulated white and brown adipocytes.
- Assessment of Ucp1 expression and cellular respiration in brown adipose tissue.
- Genetic deletion of BAFF and APRIL to study their combined effects on diet-induced obesity.
- Analysis of BAFF/APRIL effects in human adipocytes and correlation with bariatric surgery outcomes.
Main Results:
- BAFF overexpression protected against weight gain in mice, showing a dose-dependent relationship.
- BAFF stimulated lipid metabolism and lipolysis in white adipose tissue (WAT).
- BAFF increased Ucp1 expression and energy expenditure in brown adipose tissue (BAT).
- APRIL modulated WAT and BAT lipid handling similarly to BAFF.
- Combined genetic deletion of BAFF and APRIL exacerbated diet-induced obesity.
- BAFF/APRIL effects were conserved in human adipocytes and correlated with BMI reduction post-bariatric surgery.
Conclusions:
- The BAFF/APRIL axis is a critical immune regulator of weight gain and adipose tissue function.
- Targeting the BAFF/APRIL pathway may offer novel therapeutic strategies for obesity and metabolic disorders.
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