Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets
2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 47, 33997-34008 p.Article in journal (Refereed) Published
Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4.
Place, publisher, year, edition, pages
2013. Vol. 288, no 47, 33997-34008 p.
Apolipoproteins, Dyslipidemia, Lipolysis, Lipoprotein, Lipoprotein Metabolism, Triglyceride, Apolipoprotein C-I, Apolipoprotein C-III, Lipoprotein Lipase
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:umu:diva-85558DOI: 10.1074/jbc.M113.495366ISI: 000327250200041OAI: oai:DiVA.org:umu-85558DiVA: diva2:694716
FunderSwedish Research Council, 12203Swedish Heart Lung Foundation