Albumin affects the stability, oligomerization and ligand interactions of lipoprotein lipase

Background and Aims : Lipoprotein lipase (LPL), a crucial enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins, is a potential drug target for the treatment of hypertriglyceridemia. Previous studies have shown that LPL can appear in various oligomeric states and its activity is influenced by a complex ligand network. The aim of the current study was to investigate how plasma, the natural environment of the LPL action, influences its oligomerization, stability and ligand interactions.Methods: The investigations were performed by a combined use of isothermal titration calorimetry, surface plasmon resonance, negative stain transmission electron microscopy (TEM) and fluorescence correlation spectroscopy (FCS).Results: Our data showed that albumin formed a complex with LPL and had a specific effect on its stability, which could not solely be reproduced by macromolecular crowding or non-specific protein-protein interactions. TEM and FCS measurements revealed that albumin and heparin induced reversible oligomerization of LPL. Interestingly, while heparin and albumin both alone induced LPL oligomerization, their combined effect on LPL resulted in dissociation of oligomers into active LPL. Finally, our data also suggested that the formation of the oligomers protected LPL from inactivation by its physiological regulator ANGPTL4.Conclusions: The interplay between albumin and heparin could provide an additional mechanism for ensuring the dissociation of HSPG-bound LPL oligomers into active LPL upon secretion. Additionally, great consideration into LPL concentration and buffer environment should be taken in studies to distinguish between irreversible inactivation or aggregation and reversible LPL oligomer formation, which might affect interactions with various ligands and drugs. Background and Aims : Lipoprotein lipase (LPL), a crucial enzyme in the intravascular hydrolysis of triglyceride-rich lipoproteins, is a potential drug target for the treatment of hypertriglyceridemia. Previous studies have shown that LPL can appear in various oligomeric states and its activity is influenced by a complex ligand network. The aim of the current study was to investigate how plasma, the natural environment of the LPL action, influences its oligomerization, stability and ligand interactions. Methods: The investigations were performed by a combined use of isothermal titration calorimetry, surface plasmon resonance, negative stain transmission electron microscopy (TEM) and fluorescence correlation spectroscopy (FCS). Results: Our data showed that albumin formed a complex with LPL and had a specific effect on its stability, which could not solely be reproduced by macromolecular crowding or non-specific protein-protein interactions. TEM and FCS measurements revealed that albumin and heparin induced reversible oligomerization of LPL. Interestingly, while heparin and albumin both alone induced LPL oligomerization, their combined effect on LPL resulted in dissociation of oligomers into active LPL. Finally, our data also suggested that the formation of the oligomers protected LPL from inactivation by its physiological regulator ANGPTL4. Conclusions: The interplay between albumin and heparin could provide an additional mechanism for ensuring the dissociation of HSPG-bound LPL oligomers into active LPL upon secretion. Additionally, great consideration into LPL concentration and buffer environment should be taken in studies to distinguish between irreversible inactivation or aggregation and reversible LPL oligomer formation, which might affect interactions with various ligands and drugs.