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 Repjournal_title
Cell reportsauthors
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 Ddoi
10.1016/j.celrep.2014.03.062subject
Has Abstractpub_date
2014-05-22 00:00:00pages
1116-29issue
4issn
2211-1247pii
S2211-1247(14)00259-9journal_volume
7pub_type
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