FKBP51 interacts with Perilipin-A (PlinA) and the Hormone Sensitive Lipase (HSL) in white adipose tissue, and with Uncoupling Protein-1 (UCP-1) in mitochondria of brown adipose tissue

ANTONELLA LOMBARDI; JUDITH TONEATTO; MARÍA ITATÍ RODRÍGUEZ CESCHAN; GRACIELA PIWIEN-PILIPUK

Seon

Congreso; 8th International Conference on The Hsp90 Chaperone Machinery; 2016

Previously, we reported that Hsp90-binding immunophilin FKBP51 is a key regulator of adipogenesis. Here we aimed to analyze the role of FKBP51 in adipocytes. In 3T3-L1 adipocytes, FKBP51 co-localizes with PlinA and phosphorylated HSL upon induction of lipolysis. Immunoprecipitation assays show that both proteins interact with FKBP51. Adipocyte treatment with FK506 decreases FKBP51-HSL interaction, suggesting that the PPIase activity is required. Importantly, an increased and sustained phosphorylation of HSL, as well as a dramatic increase of the lipolytic activity is also evidenced. Taken together, these results suggest that FKBP51 is a negative regulator of lipolysis. In turn, FKBP51 and FKBP52 are highly expressed in murine brown adipose tissue (BAT) which is important to control body temperature. When mice are exposed to 4°C for 1 to 4 h, FKBP51 increases its expression in BAT and decreases in white adipose tissue (WAT). PAGE/SDS resolves FKBP51 into three bands we assign to phosphorylated isoforms. Lower bands increase in BAT after mice exposure to cold, suggesting FKBP51 dephosphorylation. Since FKBP51 is present in mitochondria, we postulate its interaction with UCP-1, a BAT-specific protein that catalyzes proton leak across the inner mitochondrial membrane. Co-immunoprecipitation assays in mitochondrial extracts demonstrates UCP-1?FKBP51 interaction. In summary, FKBP51 plays cardinal roles in both BAT and WAT regulating lipid homeostasis by regulating lipolysis upon its interaction with PlinA and HSL and perhaps, body-temperature when complexed with UCP-1.