Obesity is a major global health challenge, highlighting the need for physiologically relevant human models to investigate adipose tissue biology. The role of adipose tissue innervation and neuro-adipose crosstalk in metabolic regulation remains insufficiently understood, with most existing studies relying on animal models that do not fully capture human-specific features.
We developed a three-dimensional (3D) human neuro-adipose in vitro model combining human iPSC-derived neurons with human adipose stromal/stem cells (ASCs) or ASC-derived mature adipocytes. Cells were embedded in fibrin–collagen hydrogels and maintained in microfluidic culture systems for up to three weeks.
iPSC-derived neurons formed extensive networks and established direct contacts with adipocytes. Neuronal presence modulated adipose cell behavior; functional calcium imaging revealed active bidirectional signaling. Neuronal co-culture enhanced fatty acid uptake in ASCs, indicating a direct effect of neurons on adipocyte metabolic function.
These findings provide evidence that neuronal inputs can regulate both the differentiation and metabolic activity of human adipose cells, supporting emerging concepts that neuro-adipose interactions play a critical role in controlling energy balance and may contribute to the pathophysiology of obesity.