Bioenergetic programming of macrophages by the apolipoprotein A-I mimetic peptide 4F

The Biochemical Journal
Geeta DattaC Roger White

Abstract

The apoA-I (apolipoprotein A-I) mimetic peptide 4F favours the differentiation of human monocytes to an alternatively activated M2 phenotype. The goal of the present study was to test whether the 4F-mediated differentiation of MDMs (monocyte-derived macrophages) requires the induction of an oxidative metabolic programme. 4F treatment induced several genes in MDMs that play an important role in lipid metabolism, including PPARγ (peroxisome-proliferator-activated receptor γ) and CD36. Addition of 4F was associated with a significant increase in FA (fatty acid) uptake and oxidation compared with vehicle treatment. Mitochondrial respiration was assessed by measurement of the OCR (oxygen-consumption rate). 4F increased basal and ATP-linked OCR as well as maximal uncoupled mitochondrial respiration. These changes were associated with a significant increase in ΔΨm (mitochondrial membrane potential). The increase in metabolic activity in 4F-treated MDMs was attenuated by etomoxir, an inhibitor of mitochondrial FA uptake. Finally, addition of the PPARγ antagonist T0070907 to 4F-treated MDMs reduced the expression of CD163 and CD36, cell-surface markers for M2 macrophages, and reduced basal and ATP-linked OCR. These results support our h...Continue Reading

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Citations

Jul 8, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yunlan LiQingshan Li
Feb 10, 2019·The New Phytologist·Martin M Vila-AiubStephen B Powles
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May 21, 2020·International Journal of Molecular Sciences·Tariq HamidSumanth D Prabhu

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