Article ; Online: THP-1 macrophage cholesterol efflux is impaired by palmitoleate through Akt activation.
PloS one
2020 Volume 15, Issue 5, Page(s) e0233180
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. We previously showed that the phosphorylation of Akt within ... ...
| 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. We previously showed that the phosphorylation of 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. In the present study, we aimed to reveal more detail as to how the FFA component may affect Akt signalling. We show that the phosphorylation of Akt within THP-1 macrophages increases with total FFA concentration and that phosphorylation is elevated up to 18 hours. We further show that specifically the palmitoleate component of the total FFA affects Akt phosphorylation. This is tied with changes to the levels of select molecular species of phosphoinositides. We further show that the total FFA component, and specifically palmitoleate, reduces apolipoprotein A-I-mediated cholesterol efflux, and that the reduction can be reversed in the presence of the Akt inhibitor MK-2206. Overall, our data support a negative role for the FFA component of lipoprotein hydrolysis products generated by LPL, by impairing macrophage cholesterol efflux via Akt activation. |
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| MeSH term(s) | Apolipoprotein A-I/metabolism ; Cholesterol/metabolism ; Enzyme Activation/drug effects ; Heterocyclic Compounds, 3-Ring/pharmacology ; Humans ; Lipoprotein Lipase/metabolism ; Macrophages/cytology ; Macrophages/metabolism ; Palmitic Acid/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; THP-1 Cells |
| Chemical Substances | Apolipoprotein A-I ; Heterocyclic Compounds, 3-Ring ; MK 2206 ; Palmitic Acid (2V16EO95H1) ; Cholesterol (97C5T2UQ7J) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Lipoprotein Lipase (EC 3.1.1.34) |
| Keywords | covid19 |
| Language | English |
| Publishing date | 2020-05-21 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 1932-6203 |
| ISSN (online) | 1932-6203 |
| DOI | 10.1371/journal.pone.0233180 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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