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

Academic Article

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 hypothesis that the 4F-mediated differentiation of MDMs to an anti-inflammatory phenotype is due, in part, to an increase in FA uptake and mitochondrial oxidative metabolism.
  • Published In

    Keywords

  • Anti-Inflammatory Agents, Apolipoprotein A-I, Benzamides, Biomimetic Materials, Cell Differentiation, Cells, Cultured, Energy Metabolism, Fatty Acids, Gene Expression Regulation, Humans, Lipid Metabolism, Macrophages, Mitochondria, Monocytes, Oxygen Consumption, PPAR gamma, Peptides, Pyridines
  • Digital Object Identifier (doi)

    Authorlist

  • Datta G; Kramer PA; Johnson MS; Sawada H; Smythies LE; Crossman DK; Chacko B; Ballinger SW; Westbrook DG; Mayakonda P
  • Start Page

  • 517
  • End Page

  • 527
  • Volume

  • 467
  • Issue

  • 3