Free fatty acids liberated by lipoprotein lipase modulate macrophage cholesterol efflux via AKT activation in vitro

Marshall, Jenika D. (2019) Free fatty acids liberated by lipoprotein lipase modulate macrophage cholesterol efflux via AKT activation in vitro. Masters thesis, Memorial University of Newfoundland.

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Abstract

Lipoprotein lipase (LPL) is upregulated in atherosclerotic lesions and it may promote the progression of atherosclerosis, but the mechanisms behind this process are not completely understood. My laboratory has previously shown that the phosphorylation of protein kinase B (Akt) within THP-1 macrophages is increased in response to the lipid hydrolysis products generated by LPL from total lipoproteins. Notably, the free fatty acid (FFA) component was responsible for this effect. I hypothesized that activation of Akt may play a role in cellular lipid accumulation. My results show that the total FFA component results in Akt phosphorylation in a dose-dependent manner over 18 hours. Specifically, palmitoleate can significantly increase Akt phosphorylation over two hours versus control. Additionally, I expanded previous studies showing that the total FFA component significantly inhibits cholesterol efflux to apolipoprotein (apo) A-I. I further show that blocking of Akt phosphorylation using the inhibitor MK-2206 restores cholesterol efflux levels to those observed for apolipoprotein A-I alone, for cells treated with either the total complement of FFA or palmitoleate alone. Overall, my data support a negative role for LPL in macrophage lipid accumulation, which is a major contributor to atherogenesis.

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