Apolipoproteins C‐I and C‐III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets (1002.4)

Abstract

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). 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 propose a role for these apolipoproteins also in the irreversible inactivation of LPL by factors such as angptl4. Grant Funding Source: Supported by Swedish Science Council Grant 12203

Acute caloric restriction acts on the plasma proteome and reveals Apolipoprotein C1 as a signal of nutritional state and metabolic disease

“…Its role on HDL metabolism is to inhibit CETP 70,71 and activate LCAT 70 . An important APOC1 function is the inhibition of lipoprotein lipase (LPL) in the regulation of lipid metabolism [72][73][74][75] , APOC2 instead binds to the lipoprotein membrane and activates LPL 67,76 and, competes with APOC1 and APOC3 and prevents their activity 77 .…”