Apolipoprotein D modulates lipid mediators and osteopontin in an anti-inflammatory direction

Makoto Kurano1,2,3, Kazuhisa Tsukamoto4,5, Shigeo Kamitsuji6

  • 1Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Insights

Apolipoprotein D (ApoD) exhibits anti-inflammatory effects by modulating lipid mediators and osteopontin. This study elucidates ApoD

Area of Science:

  • Biochemistry
  • Immunology
  • Lipid Metabolism

Background:

  • High-density lipoprotein (HDL) is suggested to have anti-inflammatory properties.
  • The precise mechanisms underlying HDL's anti-inflammatory actions remain unclear.

Purpose of the Study:

  • To investigate the role of Apolipoprotein D (ApoD) in inflammation.
  • To explore ApoD's mechanisms in diet-induced obesity and sepsis models.
  • To analyze serum ApoD levels in human subjects.

Main Methods:

  • Utilized mouse models of diet-induced obesity and lipopolysaccharide-induced sepsis.
  • Conducted in vitro experiments to assess ApoD function.
  • Performed lipidomics analyses to identify associated lipid mediators.
  • Measured serum ApoD, osteopontin, autotaxin, and apolipoprotein M (ApoM) levels in human subjects.

Main Results:

  • Overexpression of ApoD reduced plasma IL-6 and TNF-α levels in mouse models.
  • ApoD associated with increased levels of specific fatty acids (arachidonic acid, EPA, DHA) and sphingosine 1-phosphate, while decreasing lysophosphatidic acids.
  • ApoD suppressed autotaxin expression and osteopontin, a proinflammatory adipokine, potentially via PPARγ activation.
  • Serum ApoD levels correlated negatively with osteopontin and autotaxin, and positively with ApoM.

Conclusions:

  • Apolipoprotein D (ApoD) functions as an anti-inflammatory apolipoprotein.
  • ApoD modulates lipid mediators and osteopontin towards an anti-inflammatory state.
  • Findings provide mechanistic insights into ApoD's role in inflammation.
Abstract

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