Lipoprotein lipase is active as a monomer

Area of Science:

• Biochemistry
• Molecular Biology
• Lipid Metabolism

Background:

• Lipoprotein lipase (LPL) is crucial for hydrolyzing triglycerides in lipoproteins.
• LPL has been traditionally considered active only as a homodimer, with reported sizes around 110 kDa.
• Previous studies often involved heparin, which binds and stabilizes LPL, potentially influencing its measured size.

Purpose of the Study:

• To re-evaluate the assumption that lipoprotein lipase (LPL) is exclusively active as a homodimer.
• To investigate the oligomeric state of LPL under conditions that mimic its physiological environment, particularly in the absence of stabilizing agents like heparin.

Main Methods:

• Density gradient ultracentrifugation was employed to determine the size of LPL.
• Analysis was performed on freshly secreted and purified human LPL, with and without heparin.
• LPL from different elution peaks of heparin-Sepharose chromatography was characterized.

Main Results:

• In the absence of heparin, LPL mass and activity peaked at a size consistent with monomers (near 66 kDa).
• GPIHBP1-bound LPL also appeared monomeric.
• Heparin presence increased LPL size, while inactive LPL in low-salt peaks formed aggregates, unlike active LPL in high-salt peaks.

Conclusions:

• Catalytically active lipoprotein lipase (LPL) can exist and function as a monomer.
• The presence of heparin influences LPL's apparent size, potentially leading to misinterpretations of its oligomeric state.
• This finding necessitates a revision of the current understanding of LPL regulation and activity.