Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders.

Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders. Biochem Pharmacol. 2018 Feb 17;: Authors: Gianfrancesco MA, Paquot N, Piette J, Legrand-Poels S Abstract The maintenance of the characteristic lipid compositions and physicochemical properties of biological membranes is essential for their proper function. Mechanisms allowing to sense and restore membrane homeostasis have been identified in prokaryotes for a long time and more recently in eukaryotes. A membrane remodeling can result from aberrant metabolism as seen in obesity. In this review, we describe how such lipid bilayer stress can account for the modulation of membrane proteins involved in the pathogenesis of obesity-linked inflammatory and metabolic disorders. We address the case of the Toll-like receptor 4 that is implicated in the obesity-related low grade inflammation and insulin resistance. The lipid raft-mediated TLR4 activation is promoted by an enrichment of the plasma membrane with saturated lipids or cholesterol increasing the lipid phase order. We discuss of the plasma membrane Na, K-ATPase that illustrates a new concept according to which direct interactions between specific residues and particular lipids determine both stability and activity of the pump in parallel with indirect effects of the lipid bilayer. The closely related sarco(endo)-plasmic Ca-ATPase embedded in the more fluid ER membrane seems to be more sensitive to a lipid bilay...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research