The SPHERES ERC Synergy consortium has significantly advanced our understanding of fat tissue (adipose) biology and its role in metabolic health. The project began with the development of cutting-edge models, including 3D adipocyte spheroids, which better mimic fat cells’ natural behavior compared to traditional 2D cultures. These innovations have deepened insights into lipid droplet (LD) dynamics and the diversity of adipocyte subtypes.
Key achievements include creating the Lipid Droplet Knowledge and Adipose Tissue Knowledge Portals, two central resources for LD and adipose tissue data, and applying CRISPR/Cas9 gene editing to produce precise models for studying adipose biology. The team identified distinct subtypes of white adipocytes with unique insulin responses, highlighting the complexity of adipose tissue and its impact on metabolic health. Proteomic and imaging advances have mapped molecular networks within fat cells, while studies clarified how perilipin proteins (PLINs) regulate LD stability and function.
Research also revealed that hormone-sensitive lipase (HSL) plays essential roles beyond fat breakdown, particularly in fat tissue development, using innovative knockout models. Explorations of short-chain triglycerides (TGs) uncovered their rapid breakdown at LD surfaces, which influences cellular metabolism. In brown fat, studies showed that intracellular fat breakdown is vital for heat production, identifying therapeutic targets for metabolic diseases.
Additionally, SPHERES discovered PLCXD1, a novel enzyme involved in adipocyte metabolism, and developed immortalized CD55+ precursor cells for advanced studies of adipocyte diversity. Together, these breakthroughs pave the way for new treatments targeting obesity, diabetes, and related conditions, demonstrating SPHERES’ potential to bridge science and clinical care.
