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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.
Background:
HDL has been proposed to possess anti-inflammatory properties; however, the detail mechanisms have not been fully elucidated.
Methods:
We investigated the roles of Apolipoprotein D (ApoD) in the pathogenesis of inflammation in the mouse model of diet-induced obesity and that of lipopolysaccharide-induced sepsis and the in vitro experiments. Furthermore, we analyzed serum ApoD levels in human subjects.
Results:
The overexpression of human ApoD decreased the plasma IL-6 and TNF-a levels in both mice models. Lipidomics analyses demonstrated association of ApoD with increase of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, as well as of their metabolites, and of the anti-inflammatory molecule sphingosine 1-phosphate, and decrease of proinflammatory lysophosphatidic acids and lysophosphatidylinositol. ApoD-containing lipoproteins might directly bind eicosapentaenoic acid and docosahexaenoic acid. The modulations of the lysophosphatidic acid and sphingosine 1-phosphate levels resulted from the suppression of autotaxin expression and elevation of apolipoprotein M (ApoM), respectively. Moreover, ApoD negatively regulated osteopontin, a proinflammatory adipokine. The activation of PPARg by ApoD might suppress autotaxin and osteopontin. Serum ApoD levels were negatively correlated with the serum osteopontin and autotaxin levels and, positively with serum ApoM levels.
Conclusion:
ApoD is an anti-inflammatory apolipoprotein, which modulates lipid mediators and osteopontin in an anti-inflammatory direction.
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