Fatty acids liberated from lipoproteins by lipoprotein lipase negatively influences cholesterol efflux from THP-1 macrophages

Yang, Yanbo (2014) Fatty acids liberated from lipoproteins by lipoprotein lipase negatively influences cholesterol efflux from THP-1 macrophages. Masters thesis, Memorial University of Newfoundland.

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Abstract

Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyses triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. I hypothesized that the free fatty acid (FFA) component of the products of lipoprotein hydrolysis generated by LPL promotes atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test my hypothesis, THP-1 macrophages were incubated overnight with lipoprotein hydrolysis products generated by LPL. Results showed that the hydrolysis products negatively modulated the transcripts encoding nuclear receptors, cholesterol transporters, and enzymes involved in FFA synthesis. A mixture of only purified FFA that matches those liberated by LPL yielded comparable results to those for lipoprotein hydrolysis products. Furthermore, the FFA mixture significantly attenuated apolipoprotein A-I-mediated cholesterol efflux. Overall, these data show that lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

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