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DNAJB3 Deficiency in Mice, Sex-Dependently, Exacerbates High-Fat Diet-Induced Metabolic Dysfunctions
Shadi Nejat1, Kalhara R Menikdiwela1, Olivia Iskander1
1Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas, USA.
Obesity (Silver Spring, Md.)
|November 13, 2025
Summary
DNAJB3 deficiency worsens glucose intolerance and inflammation in diet-induced obesity, particularly in females. This highlights DNAJB3
Area of Science:
- Metabolic research
- Molecular biology
- Endocrinology
Background:
- DNAJB3, a heat shock protein, is implicated in metabolic disorders.
- Obesity and type 2 diabetes (T2D) involve complex metabolic aberrations.
- Understanding DNAJB3's role is crucial for metabolic disease research.
Purpose of the Study:
- To investigate the impact of DNAJB3 deficiency on diet-induced obesity.
- To determine how DNAJB3 affects inflammation and glucose intolerance.
- To explore sex-specific effects of DNAJB3 deficiency in metabolic disease models.
Main Methods:
- DNAJB3 knockout (KO) and wild-type (WT) mice were used.
- Mice were fed high-fat (HF) or low-fat (LF) diets for 12 weeks.
- Physiological and molecular analyses were performed on various tissues.
Main Results:
- HF-fed KO females showed increased body/fat mass and impaired glucose clearance.
- DNAJB3 deficiency altered inflammatory markers and glucose transporter gene expression.
- Sex-specific differences in metabolic responses to DNAJB3 deficiency were observed.
Conclusions:
- DNAJB3 plays a significant role in glucose and metabolic regulation.
- DNAJB3 deficiency exacerbates metabolic dysfunction, especially in females.
- DNAJB3 may represent a therapeutic target for obesity and T2D.
