Immune cell Toll-like receptor 4 mediates the development of obesity- and endotoxemia-associated adipose tissue fibrosis.

Abstract:

:Adipose tissue fibrosis development blocks adipocyte hypertrophy and favors ectopic lipid accumulation. Here, we show that adipose tissue fibrosis is associated with obesity and insulin resistance in humans and mice. Kinetic studies in C3H mice fed a high-fat diet show activation of macrophages and progression of fibrosis along with adipocyte metabolic dysfunction and death. Adipose tissue fibrosis is attenuated by macrophage depletion. Impairment of Toll-like receptor 4 signaling protects mice from obesity-induced fibrosis. The presence of a functional Toll-like receptor 4 on adipose tissue hematopoietic cells is necessary for the initiation of adipose tissue fibrosis. Continuous low-dose infusion of the Toll-like receptor 4 ligand, lipopolysaccharide, promotes adipose tissue fibrosis. Ex vivo, lipopolysaccharide-mediated induction of fibrosis is prevented by antibodies against the profibrotic factor TGFβ1. Together, these results indicate that obesity and endotoxemia favor the development of adipose tissue fibrosis, a condition associated with insulin resistance, through immune cell Toll-like receptor 4.

journal_name

Cell Rep

journal_title

Cell reports

authors

Vila IK,Badin PM,Marques MA,Monbrun L,Lefort C,Mir L,Louche K,Bourlier V,Roussel B,Gui P,Grober J,Štich V,Rossmeislová L,Zakaroff-Girard A,Bouloumié A,Viguerie N,Moro C,Tavernier G,Langin D

doi

10.1016/j.celrep.2014.03.062

subject

Has Abstract

pub_date

2014-05-22 00:00:00

pages

1116-29

issue

4

issn

2211-1247

pii

S2211-1247(14)00259-9

journal_volume

7

pub_type

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