An ex vivo Mouse Model for High-Fat Diet-Like Adipose Tissue Inflammation

Area of Science:

• Metabolic Research
• Immunology
• Adipose Tissue Biology

Background:

• High-fat diet (HFD) feeding induces inflammation in visceral adipose tissue (VAT).
• Understanding the cellular and molecular mechanisms of VAT inflammation is crucial for metabolic disease research.
• Existing in vivo models often require prolonged HFD exposure and may not fully isolate specific inflammatory pathways.

Purpose of the Study:

• To develop and validate an ex vivo mouse model of VAT inflammation that recapitulates key features of HFD-induced changes.
• To provide a physiologically relevant and reproducible platform for investigating adipose tissue (AT) inflammation.
• To facilitate the study of adipocyte death, immune cell dynamics, and therapeutic interventions in AT inflammation.

Main Methods:

• Culture of small VAT explants from lean mice for 7-10 days.
• Observation of spontaneous development of inflammatory phenotype, including crown-like structures (CLS) and metabolically activated macrophages (MMes).
• Assessment of inflammatory cytokine production and preservation of AT architecture.

Main Results:

• The ex vivo model spontaneously develops an inflammatory phenotype similar to HFD-fed animals.
• Key hallmarks of obesity-related inflammation, such as CLS formation and MMe accumulation, are observed.
• The model preserves AT architecture and supports various downstream analyses, including molecular and cellular assays.

Conclusions:

• This ex vivo VAT explant model effectively recapitulates key inflammatory features of HFD-induced obesity.
• The model is versatile, cost-effective, and aligns with the 3R principles for reducing animal use.
• It serves as a valuable platform for studying AT inflammation, adipocyte death, immune cell responses, and potential therapeutic strategies.