Linking adipocyte lipid storage determinants to common metabolic disorders

Adipocytes residing in white adipose tissue are cells specialized in storing energy in the form of lipids in organelles called lipid droplets (LDs).

The hydrophobic LD core, containing neutral lipids such as triacylglycerols and cholesterol esters, is shielded from the cell’s aqueous cytoplasm by a phospholipid monolayer in which a specific set of proteins are embedded. These LD proteins allow local synthesis and degradation of lipids in order to match the energy demand of the cell.

Because more than 90% of the adipocyte cell volume is comprised by the LD, overwhelming the storage capacity of adipocytes results in large (hypertrophic) cells, a phenotype which in clinical studies is strongly associated with insulin resistance, type 2 diabetes and dyslipidemia.

By combining advanced molecular techniques, including perturbation screening, high-content image analyses and subcellular proteomics, with state-of-the-art clinical research, a translational approach will be applied herein to identify adipocyte lipid storage determinants and to link them to common metabolic disorders such as insulin resistance, type 2 diabetes and dyslipidemia.

The results generated in this project may uncover novel mechanisms controlling cellular lipid homeostasis and provide new therapeutic avenues to treat common metabolic disorders.