Bioenergetic Programming Of Macrophages By The Apolipoprotein A-I Mimetic Peptide 4F

The apolipoprotein (apo)A-I mimetic peptide 4F favors the differentiation of human monocytes to an alternatively-activated M2 phenotype. The goal of the current study was to test whether the 4F-mediated differentiation of monocyte-derived macrophages (MDMs) requires the induction of an oxidative metabolic program. 4F treatment induced several genes in MDMs that play an important role in lipid metabolism, including peroxisome proliferator-activated receptor γ (PPARγ) and CD36. Addition of 4F was associated with a significant increase in fatty acid (FA) uptake and oxidation compared to vehicle treatment. Mitochondrial respiration was assessed by measurement of oxygen consumption rate (OCR). 4F increased basal and ATP-linked OCR as well as maximal uncoupled mitochondrial respiration. These changes were associated with a significant increase in mitochondrial membrane potential (ΔΨm). 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 hypothesis that the 4F-mediated differentiation of MDMs to an anti-inflammatory phenotype is due, in part, to an increase in FA acid uptake and mitochondrial oxidative metabolism

Source: BJ Energy - March 5, 2015 Category: Biochemistry Authors: G Datta, P A Kramer, M S Johnson, H Sawada, L E Smythies, D K Crossman, B Chacko, S W Ballinger, D G Westbrook, P Mayakonda, G M Anantharamaiah, V M Darley-Usmar, C Roger White Tags: BJ Energy Source Type: research