Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue

• DOI: 10.1073/pnas.0604026103
• Publication Date: 2006-11-07T01:54:23Z
• Authors: Valentina Sukonina; Aivar Lookene; Thomas Olivecrona; Gunilla Olivecrona
• Keywords: Catabolism

Lipoprotein lipase (LPL) has a central role in lipoprotein metabolism to maintain normal levels blood and, through tissue specific regulation of its activity, determine when and what tissues triglycerides are unloaded. Recent data indicate that angiopoietin-like protein (Angptl)-4 inhibits LPL retards catabolism. We demonstrate here the N-terminal coiled-coil domain Angptl-4 binds transiently interaction results conversion enzyme from catalytically active dimers inactive, but still folded, monomers with decreased affinity for heparin. Inactivation occurred less than equimolar ratios LPL, was strongly temperature-dependent, did not consume Angptl-4. Furthermore, we show mRNA rat adipose turns over rapidly changes abundance inversely correlated both during fed-to-fasted fasted-to-fed transitions. conclude is fasting-induced controller tissue, acting extracellularly on native conformation an unusual fashion, like unfolding molecular chaperone.