Article (Scientific journals)
Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders.
Gianfrancesco, Marco; Paquot, Nicolas; Piette, Jacques et al.
2018In Biochemical Pharmacology
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Keywords :
ER stress; Lipid; Membrane; Metabolism; Obesity
Abstract :
[en] 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 bilayer stress as demonstrated by its inactivation in cholesterol-loaded macrophages or its inhibition mediated by an increased PtdCho/PtdEtn ratio in obese mice hepatocytes. Finally, we describe the model recently proposed for the activation of the conserved IRE-1 protein through alterations in the ER membrane lipid packing and thickness. Such IRE-1 activation could occur in response to abnormal lipid synthesis and membrane remodeling as observed in hepatocytes exposed to excess nutrients. Since the IRE-1/XBP1 branch also stimulates the lipid synthesis, this pathway could create a vicious cycle "lipogenesis-ER lipid bilayer stress-lipogenesis" amplifying hepatic ER pathology and the obesity-linked systemic metabolic defects.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Gianfrancesco, Marco ;  Université de Liège - ULiège > Département des sciences de la santé publique > Diabétologie, nutrition et maladies métaboliques
Paquot, Nicolas ;  Université de Liège - ULiège > Département des sciences de la santé publique > Diabétologie, nutrition et maladies métaboliques
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Legrand, Sylvie ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Language :
English
Title :
Lipid bilayer stress in obesity-linked inflammatory and metabolic disorders.
Publication date :
17 February 2018
Journal title :
Biochemical Pharmacology
ISSN :
0006-2952
eISSN :
1873-2968
Publisher :
Elsevier, Netherlands
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2018 Elsevier Inc. All rights reserved.
Available on ORBi :
since 28 May 2018

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