Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis

Mario Ruiz (), Ranjan Devkota, Dimitra Panagaki, Per-Olof Bergh, Delaney Kaper, Marcus Henricsson, Ali Nik, Kasparas Petkevicius, Johanna L. Höög, Mohammad Bohlooly-Y, Peter Carlsson, Jan Borén and Marc Pilon ()
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Mario Ruiz: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Ranjan Devkota: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Dimitra Panagaki: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Per-Olof Bergh: Institute of Medicine, Univ. of Gothenburg
Delaney Kaper: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Marcus Henricsson: Institute of Medicine, Univ. of Gothenburg
Ali Nik: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Kasparas Petkevicius: Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca
Johanna L. Höög: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Mohammad Bohlooly-Y: Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca
Peter Carlsson: Dept.Chemistry and Molecular Biology, Univ. Gothenburg
Jan Borén: Institute of Medicine, Univ. of Gothenburg
Marc Pilon: Dept.Chemistry and Molecular Biology, Univ. Gothenburg

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: Abstract Cells and organisms require proper membrane composition to function and develop. Phospholipids are the major component of membranes and are primarily acquired through the diet. Given great variability in diet composition, cells must be able to deploy mechanisms that correct deviations from optimal membrane composition and properties. Here, using lipidomics and unbiased proteomics, we found that the embryonic lethality in mice lacking the fluidity regulators Adiponectin Receptors 1 and 2 (AdipoR1/2) is associated with aberrant high saturation of the membrane phospholipids. Using mouse embryonic fibroblasts (MEFs) derived from AdipoR1/2-KO embryos, human cell lines and the model organism C. elegans we found that, mechanistically, AdipoR1/2-derived sphingosine 1-phosphate (S1P) signals in parallel through S1PR3-SREBP1 and PPARγ to sustain the expression of the fatty acid desaturase SCD and maintain membrane properties. Thus, our work identifies an evolutionary conserved pathway by which cells and organisms achieve membrane homeostasis and adapt to a variable environment.

Date: 2022
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DOI: 10.1038/s41467-022-34931-0

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