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 that promotes fatty acid desaturation via sterol regulatory-element binding protein and peroxisome proliferator– activated receptor gamma (1, 2, 3).
Mouse embryonic fibroblasts lacking AdipoR1 and AdipoR2 (AdipoR1/2 double KO) and treated with palmitic acid form abnormal endoplasmic reticulum 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 (1). These endoplasmic reticulum structures are not present in basal conditions (1).
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 (1).
Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article.
Acknowledgments
Author contributions
M. R. conceptualization; M. R. and D. P. investigation; J. L. H. and M. P. resources; M. R. and D. P. writing–original draft; M. R., D. P., J. L. H., and M. P. writing–review & editing; J. L. H. and M. P. supervision.
Funding and additional information
This work was supported by the Swedish Research Council (Vetenskapsrådet Dnr: 2020-03300 [to M. P.] and 2015-00560 to Richard Neutze (D.P. work) and Åke Wiberg Stiftelse (to M. R.).
Contributor Information
Mario Ruiz, Email: mario.ruiz@gu.se.
Marc Pilon, Email: marc.pilon@cmb.gu.se.
References
- 1.Ruiz M., Devkota R., Panagaki D., Bergh P.O., Kaper D., Henricsson M., et al. Sphingosine 1-phosphate mediates adiponectin receptor signaling essential for lipid homeostasis and embryogenesis. Nat. Commun. 2022;13:7162. doi: 10.1038/s41467-022-34931-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ruiz M., Palmgren H., Henricsson M., Devkota R., Jaiswal H., Maresca M., et al. Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids. Biochim. Biophys. Acta Mol. Cell Biol. Lipids. 2021;1866 doi: 10.1016/j.bbalip.2021.158884. [DOI] [PubMed] [Google Scholar]
- 3.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. doi: 10.1194/jlr.M092494. [DOI] [PMC free article] [PubMed] [Google Scholar]