Exogenous supplement of N-acetylneuraminic acid improves macrophage reverse cholesterol transport in apolipoprotein E-deficient mice

BACKGROUND: N-acetylneuraminic acid (NANA) is the major form of sialic acid in mammals, and the plasma NANA level is increased in patients with cardiovascular diseases. Exogenous supplement of NANA has been demonstrated to reduce hyperlipidaemia and the formation of atherosclerotic lesions; however, the underlying mechanisms have not yet been clarified. The aim of this study is to investigate whether exogenous supplement of NANA improves reverse cholesterol transprot (RCT) in vivo. METHODS: Apolipoprotein E-deficient mice fed a high-fat diet were used to investigate the effect of NANA on RCT by [(3)H]-cholesterol-loaded macrophages, and the underlying mechanism was further investigated by various molecular techniques using fenofibrate as a positive control. RESULTS: Our novel results demonstrated that exogenous supplement of NANA significantly improved [(3)H]-cholesterol transfer from [(3)H]-cholesterol-loaded macrophages to the plasma (an increase of > 42.9%), liver (an increase of 35.8%), and finally to the feces (an increase of 50.4% from 0 to 24 h) for excretion in apolipoprotein E-deficient mice fed a high-fat diet. In addition, NANA up regulated the protein expression of ATP-binding cassette (ABC) G1 and peroxisome proliferator-activated receptor α (PPARα), but not the protein expression of ABCA1and scavenger receptor B type 1 in the liver. Therefore, the underlying mechanism of NANA in improving RCT may be partially due to the elevated protein levels of PPARα and ABCG1. CONCLUSION: Exogenous supplement of NANA improves RCT in apolipoprotein E-deficient mice fed a high-fat diet mainly by improving the protein expression of PPARα and ABCG1. These results are helpful in explaining the lipid-lowering effect of NANA.