Critical Evaluation of Adipogenic Cell Models: Impact of the Receptor Toolkit on Adipogenic Potential

Adipocyte cell models are essential for investigating adipogenesis, yet methodological inconsistencies pose challenges to obtaining reproducible and physiologically relevant results. Murine cell lines, such as 3T3-L1 and OP9, are commonly utilized due to their established adipogenic capabilities. However, differences in its metabolic, genetic regulation, and receptor signaling raise concerns about their applicability to human adipose biology. Human-derived models, including mesenchymal stem cells (hMSCs) and preadipocyte cell lines, offer a closer approximation to in vivo adipogenesis but display significant variability in differentiation efficiency. This variability is often compounded by heterogeneous differentiation protocols, variations in cell confluence, and unstandardized pharmacological induction strategies. A pivotal factor influencing adipogenic potential is the receptor toolkit, which dictates cellular responses to differentiation stimuli. This study systematically evaluates key receptors—PPARγ, glucocorticoid receptors (GR), insulin receptor (IR), thyroid hormone receptors (TR), estrogen receptors (ER), and adenosine receptors (AR)—across commonly used adipocyte models to assess their roles in adipogenic regulation. Additionally, we examine the impact of pharmacological agents capable of inducing adipogenesis (adipogens) and the methodological inconsistencies that contribute to variations in adipocyte differentiation. By addressing these factors, we aim to elucidate the extent to which receptor variability influences experimental outcomes and propose a more structured approach to interpreting adipogenesis research. This critical assessment underscores the need for greater methodological transparency and receptor profiling to enhance the reliability of adipocyte models in metabolic research. Standardizing differentiation methodologies while accounting for receptor diversity will be essential for refining in vitro models and improving their translational potential in the study of obesity, diabetes, and other metabolic disorders.