Lipid Trends

A paper entitled "Lipidomic and biophysical homeostasis of mammalian membranes counteracts dietary lipid perturbations to maintain cellular fitness" (https://www.nature.com/articles/s41467-020-15203-1) discusses mechanisms of mammalian cellular homeostasis, in particular of membrane biophysical properties. The authors show that mammalian cells possess an autonomous, essential response designed to restore membrane physical properties following perturbations from the diet, and that this response is mediated by cholesterol. Membrane adaptiveness is a fundamental and ubiquitous response of non-thermoregulating organisms across the tree of life, from prokaryotes to cold-blooded animals. In such organisms, changes in body temperature affect membrane fluidity, which must in turn be compensated by modulation of lipid composition to maintain functional membrane phenotypes. In mammals, which do not experience large-scale changes in body temperature, the existence of such membrane responsiveness has not been widely investigated. However, it is a well-established but under-appreciated fact that mammalian membranes are challenged by dietary inputs, as dietary fatty acids and cholesterol are directly and robustly incorporated into cell membranes. The paper reports that such perturbations induce near-simultaneous, ubiquitous remodeling of cellular lipidomes in various mammalian cells and that this lipid remodeling leads to re-normalization of membrane properties. The response is mediated in part by a member of the SREBP family of lipid master regulators, with cholesterol regulation playing an important role. Finally, inhibition of this response causes cytotoxicity when membrane homeostasis is challenged by dietary lipids. These results reveal an essential mechanism of mammalian cellular homeostasis - analogous to prokaryotic homeoviscous adaptation - wherein cells remodel their lipidomes in response to dietary lipid inputs in order to preserve functional membrane phenotypes.