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RAGE Knockout Mitigates Diet-Induced Obesity and Metabolic Disruption
Isabelle L Palmer1, Genevieve Parker1, Alden T Chiu1
1Department of Cell Biology and Physiology, Brigham Young University, Provo, UT 84602, USA.
Metabolites
|August 27, 2025
Summary
Mice lacking the receptor for advanced glycation end products (RAGE) resisted diet-induced obesity. RAGE knockout mice showed reduced weight gain, increased energy expenditure, and lower inflammation when fed a Western diet.
Area of Science:
- Metabolic research
- Obesity research
- Inflammation research
Background:
- The receptor for advanced glycation end products (RAGE) is linked to obesity and metabolic dysfunction.
- The specific role of RAGE in diet-induced obesity requires further elucidation.
Purpose of the Study:
- To investigate the metabolic effects of RAGE knockout (RAGE KO) in mice on a Western diet (WD).
Main Methods:
- Utilized RAGE KO mice and wild-type (WT) littermates fed a WD.
- Conducted indirect calorimetry and mitochondrial respiration assays.
- Measured body weight, adipocyte size, and systemic inflammation markers (e.g., TNF-α).
Main Results:
- RAGE KO mice exhibited reduced body weight gain and adipocyte size compared to WT mice on a WD.
- RAGE KO mice demonstrated increased oxygen consumption and locomotor activity, indicating higher energy expenditure.
- Lower levels of systemic inflammation markers were observed in RAGE KO mice, suggesting reduced inflammatory responses.
Conclusions:
- RAGE plays a critical role in metabolic homeostasis.
- RAGE deletion confers resistance to obesity and metabolic disruption induced by a WD.
- Targeting RAGE presents a potential therapeutic strategy for obesity and associated metabolic disorders.
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