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Lipid droplet hypertrophy : the link between adipocyte dysfunction and cardiometabolic diseases

Project description

Multi-level dynamics of adipocyte hypertrophy

Adipocyte hypertrophy is a condition associated with larger than normal lipid droplets (LDs), the adipocyte organelles that store energy in the form of triglycerides. Adipocyte hypertrophy is irrespective of body fat and causes a wide range of pathological conditions including cardiometabolic diseases. The scope of the EU-funded SPHERES project is to investigate the hypothesis that disturbances in the interaction between LD proteins and LD lipid composition lead to adipocyte hypertrophy. Run by a multi-disciplinary network of experts, the project will develop beyond-state-of-the-art models and methods to study the formation and maintenance of large adipocyte LDs. The work will pave the way for a better understanding of the underlying mechanisms of adipocyte hypertrophy as well as the identification of therapeutic strategies targeting adipocytes.


The goal of SPHERES is to understand the dynamics and consequences of adipocyte hypertrophy (enlargement) through investigation of its large lipid droplet (LD). The adipocyte LD is a unique organelle specialized in storing energy in triglycerides (TGs). Its surface is composed of a phospholipid monolayer and specific LD-associated proteins (such as perilipins, CIDEs and lipases), which jointly regulate LD stability and TG turnover. Adipocyte hypertrophy due to an increase in LD size may, irrespective of body fat mass, cause a wide range of pathological conditions, notably cardiometabolic diseases. SPHERES PIs (Langin, Rydén, Antonny) postulate that disturbances in the interactions between LD proteins and LD lipid composition lead to adipocyte hypertrophy and its deleterious consequences. We have identified three fundamental unanswered questions: what determines the unique structure and dynamics of large LD; why does increased LD size alter the functional phenotype of the adipocyte; which factors cause inter-individual variations in LD size. To address these questions, SPHERES gathers expertise in clinical and cellular studies on human adipocytes, in/ex vivo investigations in mouse models, and biophysical analyses of LDs. At the core of this application is the development of beyond-state-of-the-art models and methods (spheroid cultures, native large LD preparation and reconstitution, proximity labelling of LD proteins, gene editing in cell and mouse models, and advanced LD imaging), only achievable through joint integrated effort of the PIs and co-workers. Spanning from molecular, cellular to the whole-body level, SPHERES will link new knowledge on the formation and maintenance of large adipocyte LDs to the deleterious impact of adipocyte hypertrophy. Altogether, SPHERES has a strong potential to discover novel pathogenic mechanisms, leading to a better understanding of highly prevalent diseases and identification of therapeutic strategies targeting adipocytes.


Host institution

Net EU contribution
€ 3 326 680,92
31062 Toulouse Cedex 9

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Occitanie Midi-Pyrénées Haute-Garonne
Activity type
Higher or Secondary Education Establishments
Total cost
€ 3 537 143,00

Beneficiaries (5)