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Striking Membrane Defects in AdipoR-Deficient Cells

Open AccessPublished:January 19, 2023DOI:https://doi.org/10.1016/j.jlr.2023.100335
      Membrane homeostasis defects likely underly numerous conditions. AdipoR1 and AdipoR2 sense excesses of saturated fatty acids in phospholipids and correct such imbalance by generating sphingosine 1-phospate (S1P) that promotes fatty acid desaturation via SREBP and PPARγ (
      • Ruiz M.
      • Devkota R.
      • Panagaki D.
      • Bergh P.O.
      • Kaper D.
      • Henricsson M.
      • Nik A.
      • Petkevicius K.
      • Hoog J.L.
      • Bohlooly Y.M.
      • Carlsson P.
      • Boren J.
      • Pilon M.
      Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
      ,
      • Ruiz M.
      • Palmgren H.
      • Henricsson M.
      • Devkota R.
      • Jaiswal H.
      • Maresca M.
      • Bohlooly Y.M.
      • Peng X.R.
      • Boren J.
      • Pilon M.
      Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids.
      ,
      • Ruiz M.
      • Stahlman M.
      • Boren J.
      • Pilon M.
      AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin.
      ).
      Mouse embryonic fibroblasts lacking AdipoR1 and 2 (AdipoR1/2 DKO) and treated with palmitic acid form abnormal ER-structures: long straight lines visualized by confocal microscopy (white arrows), whereas electron micrographs reveal distinctive spirals of packed membranes (red arrows) that are likely cross-sections of the lines seen with Laurdan staining (
      • Ruiz M.
      • Devkota R.
      • Panagaki D.
      • Bergh P.O.
      • Kaper D.
      • Henricsson M.
      • Nik A.
      • Petkevicius K.
      • Hoog J.L.
      • Bohlooly Y.M.
      • Carlsson P.
      • Boren J.
      • Pilon M.
      Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
      ). These ER structures are not present in basal conditions (
      • Ruiz M.
      • Devkota R.
      • Panagaki D.
      • Bergh P.O.
      • Kaper D.
      • Henricsson M.
      • Nik A.
      • Petkevicius K.
      • Hoog J.L.
      • Bohlooly Y.M.
      • Carlsson P.
      • Boren J.
      • Pilon M.
      Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
      ).

      Equipment and reagents

      LSM880 confocal microscope with Airyscan (Zeiss), Laurdan dye, palmitic acid, Wohlwend Compact 3 high pressure freezer, Leica AFS, Tecnai T12 transmission electron microscope, Ceta CMOS 16M camera (
      • Ruiz M.
      • Devkota R.
      • Panagaki D.
      • Bergh P.O.
      • Kaper D.
      • Henricsson M.
      • Nik A.
      • Petkevicius K.
      • Hoog J.L.
      • Bohlooly Y.M.
      • Carlsson P.
      • Boren J.
      • Pilon M.
      Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
      ).

      Conflict of interest

      none.

      References

        • Ruiz M.
        • Devkota R.
        • Panagaki D.
        • Bergh P.O.
        • Kaper D.
        • Henricsson M.
        • Nik A.
        • Petkevicius K.
        • Hoog J.L.
        • Bohlooly Y.M.
        • Carlsson P.
        • Boren J.
        • Pilon M.
        Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
        Nat Commun. 2022; 13: 7162
        • Ruiz M.
        • Palmgren H.
        • Henricsson M.
        • Devkota R.
        • Jaiswal H.
        • Maresca M.
        • Bohlooly Y.M.
        • Peng X.R.
        • Boren J.
        • Pilon M.
        Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids.
        Biochim Biophys Acta Mol Cell Biol Lipids. 2021; 1866158884
        • Ruiz M.
        • Stahlman M.
        • Boren J.
        • Pilon M.
        AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin.
        J Lipid Res. 2019; 60: 995-1004