Emerging models for studying adipose tissue metabolism

Abstract

Understanding adipose metabolism is essential for addressing obesity and related health concerns. However, the ethical and scientific pressure to animal testing, aligning with the 3Rs, has triggered the implementation of diverse alternative models for analysing anomalies in adipose metabolism. In this review, we will address this issue from various perspectives. Traditional adipocyte cell cultures, whether animal or human-derived, offer a fundamental starting point. These systems have their merits but may not fully replicate in vivo complexity. Established cell lines are valuable for high-throughput screening but may lack the authenticity of primary-derived adipocytes, which closely mimic native tissue. To enhance model sophistication, spheroids have been introduced. These three-dimensional cultures better mimicking the in vivo microenvironment, enabling the study of intricate cell-cell interactions, gene expression, and metabolic pathways. Organ-on-a-chip (OoC) platforms take this further by integrating multiple cell types into microfluidic devices, simulating tissue-level functions. Adipose-OoC (AOoC) provides dynamic environments with applications spanning drug testing to personalized medicine and nutrition. Beyond in vitro models, genetically amenable organisms (Caenorhabditis elegans, Drosophila melanogaster, and zebrafish larvae) have become powerful tools for investigating fundamental molecular mechanisms that govern adipose tissue functions. Their genetic tractability allows for efficient manipulation and high-throughput studies. In conclusion, a diverse array of research models is crucial for deciphering adipose metabolism. By leveraging traditional adipocyte cell cultures, primary-derived cells, spheroids, AOoCs, and lower organism models, we bridge the gap between animal testing and a more ethical, scientifically robust, and human-relevant approach, advancing our understanding of adipose tissue metabolism and its impact on health.

Keywords: Adipocytes; C. elegans; Co-culture; D. melanogaster; Spheroids; Zebrafish larvae.