support-information-section).

With obesity and its comorbidities continuing to rise, we urgently need to improve our understanding of what mechanisms trigger the white adipose tissue to become dysfunctional in response to over-feeding. The recent invent of 3D culturing models has produced several noteworthy protocols for differentiating unilocular adipocytes in vitro , promising to revolutionize the obesity research field by providing more representative adipose tissue models for such mechanistic studies. In parallel, these 3D models provide important insights to how profoundly the microenvironment influences adipocyte differentiation and morphology. This commentary highlights some of the most recent 3D models, including human unilocular vascularized adipocyte spheroids (HUVASs), developed by our lab. We discuss recent developments in the field, provide further insights to the importance of the microvasculature for adipocyte maturation, and summarize what challenges remain to be solved before we can achieve a culture model that fully recapitulates all aspects of human white adipocyte biology in vitro . Taken together, the commentary highlights important recent advances regarding 3D adipocyte culturing and underlines the many advantages these models provide over traditional 2D cultures, with the aim of convincing more laboratories to switch to 3D models.