Premium
Monounsaturated Fatty Acids Impede Inflammation Partially Through Activation of AMPK
Author(s) -
Lyons Claire L,
Finucane Orla F,
Murphy Aoife M,
Cooke Aoife A,
Viollet Benoit,
Vieira Pedro M,
Oldham William,
Kahn Barbara B,
Roche Helen M
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.296.5
Subject(s) - ampk , inflammation , chemistry , medicine , macrophage , endocrinology , fatty acid , glycolysis , biochemistry , biology , metabolism , phosphorylation , protein kinase a , in vitro
AMPK, a critical metabolic sensor exhibits anti‐inflammatory properties. Recently we demonstrated that AMPK played an important role in modulating IL‐1β‐induced inflammation in response to different dietary fatty acids, wherein oleic acid (OA) impeded both ATP and palmitic acid (PA) induced IL‐1β secretion from macrophages coincident with increased levels of phosphorylated AMPK. The aim of this study is to further define the macrophage inflammatory and metabolic phenotype in the presence of monounsaturated fatty acids (MUFA) and to determine how MUFA‐activated AMPK impedes saturated fatty acid (SFA)‐induced inflammation. The inflammatory and metabolic phenotype of bone marrow derived macrophages treated with OA and PA or a combination of both, with or without LPS stimulation was measured by ELISA and seahorse XF24 analyser. Western blot analysis was performed on adipose tissue harvested from mice fed a 45% SFA (palm oil) or 45% MUFA (olive oil) –high‐fat diet for 16–32 weeks. The magnitude of inflammation in M1 polarised macrophages was reduced when cultured in the presence of OA compared to PA as demonstrated by reduced TNFα cytokine secretion from OA treated cells. On the other hand, lack of AMPK abolished the OA effect. OA impeded LPS‐induced NFκB activation and reduced pro‐IL‐1β levels similar to the AMPK agonist AICAR. Corresponding alterations were observed in the macrophage metabolic phenotype wherein cells treated with PA had reduced ATP production and increased glycolysis and glycolytic capacity compared to cells treated with OA. Additionally macrophages treated with PA had reduced coupling efficiency compared to those treated with OA. Importantly, pre‐treatment with OA reduced PA induced glycolysis and glycolytic capacity and increased cell coupling efficiency. In mice switched from a SFA to a MUFA high fat diet, the levels of phosphorylated AMPK were increased in the adipose tissue compared to animals maintained on a SFA high‐fat diet. Correspondingly both immature and secreted forms of adipose IL‐1β were reduced in these mice, and hyperinsulinemia was also reduced. In conclusion, macrophages exposed to MUFA exhibit alleviated inflammation in response to pro‐inflammatory stimuli. Preliminary data point towards a critical role for AMPK in this process whereby, AMPK activation may mitigate inflammation, by inhibiting NFκB activity and consequently impeding priming of pro‐IL‐1β. Critically, MUFA‐treated cells indicate a greater capacity to respond to stress, exemplified by reduced glycolysis and increased oxidative phosphorylation compared to PA treated cells. Overall, these results indicate that MUFA may have the ability to both impede and reverse SFA induced inflammation, via AMPK. This may shed light into new possibilities for both the prevention and treatment of chronic inflammatory related diseases, such as obesity‐induced insulin resistance and type 2 diabetes. This research is funded by the Science Foundation Principal Investigator Award (11/PI/1119). Orla F Finucane was awarded an Albert Reynold Travel Fellowship from the European Foundation for the study of Diabetes for research conducted in BIDMC, Harvard Medical School, Boston, MA, Boston, USA.