Functional characterization of obesity using advanced 3D in vitro adipose tissue models

Area of Science:

• Biomedical Engineering
• Metabolic Disease Research
• Adipose Tissue Biology

Background:

• Obesity is a complex systemic disease driving the global metabolic syndrome epidemic.
• Adipose tissue dysfunction, particularly in adipocytes, is central to obesity's pathogenesis.
• Current understanding of obesity mechanisms within adipose tissue is limited.

Purpose of the Study:

• To review cutting-edge three-dimensional (3D) adipose tissue models as New Approach Methodologies (NAMs) for obesity research.
• To highlight the capabilities of 3D models in recapitulating obese adipocyte phenotypes.
• To discuss challenges and opportunities in utilizing 3D models for drug discovery and therapeutic interventions.

Main Methods:

• Utilizing revolutionary 3D adipocyte models to mimic in vivo obese adipocyte characteristics (hypertrophic, lipid-laden).
• Comparing 3D models to traditional 2D monolayer systems, noting the superior retention of adipocytes in 3D.
• Employing diverse functional assays within 3D platforms to study obesity hallmarks and therapeutic efficacy.

Main Results:

• 3D in vitro platforms effectively replicate the dysfunctional obese adipocyte phenotype, unlike 2D systems.
• These sophisticated NAMs enable dissection of obesity's multifactorial nature.
• 3D models provide a powerful tool for validating disease hallmarks and assessing therapeutic interventions.

Conclusions:

• 3D adipose tissue models represent a significant advancement for in vitro obesity research.
• Integrating multiple readouts from 3D models is crucial for uncovering novel adipocyte-targeting mechanisms.
• These platforms hold transformative potential for accelerating biological and drug target discovery in obesity, paving the way for next-generation therapies.