RRC ID 76284
Author Ruiz M, Devkota R, Panagaki D, Bergh PO, Kaper D, Henricsson M, Nik A, Petkevicius K, Höög JL, Bohlooly-Y M, Carlsson P, Borén J, Pilon M.
Title Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis.
Journal Nat Commun
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.
Volume 13(1)
Pages 7162
Published 2022-11-22
DOI 10.1038/s41467-022-34931-0
PII 10.1038/s41467-022-34931-0
PMID 36418331
PMC PMC9684441
MeSH Animals Caenorhabditis elegans* Embryonic Development / genetics Fibroblasts Homeostasis Humans Lysophospholipids Mice Receptors, Adiponectin* / genetics
Resource
C.elegans tm3410