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

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...

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Bibliographic Details
Published in:	Nature communications 2020-03, Vol.11 (1), p.1339-1339, Article 1339
Main Authors:	Levental, Kandice R, Malmberg, Eric, Symons, Jessica L, Fan, Yang-Yi, Chapkin, Robert S, Ernst, Robert, Levental, Ilya
Format:	Article
Language:	eng
Subjects:	Adaptation Animals Biocompatibility Biophysics Buffers Cell culture Cell Line Cell Membrane - chemistry Cell Membrane - metabolism Cholesterol Cytotoxicity Diet Dietary Fats - metabolism Fatty acids Fatty Acids - chemistry Fatty Acids - metabolism Female Fluidity Homeostasis Humans Lipidomics Lipids Maintenance Mammals Membrane Fluidity Membrane Lipids - chemistry Membrane Lipids - metabolism Membrane permeability Membranes Mice Mice, Inbred C57BL Phenotypes Physical properties Physicochemical properties Physiology Polyunsaturated fatty acids Rats Toxicity
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Summary:	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.
ISSN:	2041-1723 2041-1723