Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness

Nat Commun. 2020 Mar 12;11(1):1339. doi: 10.1038/s41467-020-15203-1.


Proper membrane physiology requires maintenance of biophysical properties, which must be buffered from external perturbations. While homeostatic adaptation of membrane fluidity to temperature variation is a ubiquitous feature of ectothermic organisms, such responsive membrane adaptation to external inputs has not been directly observed in mammals. Here, we report that challenging mammalian membranes by dietary lipids leads to robust lipidomic remodeling to preserve membrane physical properties. Specifically, exogenous polyunsaturated fatty acids are rapidly incorporated into membrane lipids, inducing a reduction in membrane packing. These effects are rapidly compensated both in culture and in vivo by lipidome-wide remodeling, most notably upregulation of saturated lipids and cholesterol, resulting in recovery of membrane packing and permeability. Abrogation of this response results in cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential mammalian mechanism for membrane homeostasis wherein lipidome remodeling in response to dietary lipid inputs preserves functional membrane phenotypes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biophysics
  • Cell Line
  • Cell Membrane / chemistry*
  • Cell Membrane / metabolism
  • Dietary Fats / metabolism*
  • Fatty Acids / chemistry
  • Fatty Acids / metabolism
  • Female
  • Homeostasis
  • Humans
  • Lipidomics
  • Membrane Fluidity
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Rats


  • Dietary Fats
  • Fatty Acids
  • Membrane Lipids