Immune Cell Toll-like Receptor 4 Mediates the Development of Obesity- and Endotoxemia-Associated Adipose Tissue Fibrosis

6533b7dbfe1ef96bd1271603

RESEARCH PRODUCT

Immune Cell Toll-like Receptor 4 Mediates the Development of Obesity- and Endotoxemia-Associated Adipose Tissue Fibrosis

Jacques Grober Jacques Grober Vladimir Stich Philippe Gui Philippe Gui Corinne Lefort Corinne Lefort Geneviève Tavernier Geneviève Tavernier Virginie Bourlier Virginie Bourlier Isabelle K. Vila Isabelle K. Vila Lenka Rossmeislová Lucile Mir Lucile Mir Katie Louche Katie Louche Anne Bouloumié Anne Bouloumié Nathalie Viguerie Nathalie Viguerie Pierre Marie Badin Pierre Marie Badin Balbine Roussel Balbine Roussel Alexia Zakaroff-girard Alexia Zakaroff-girard Dominique Langin Cedric Moro Cedric Moro Marie Adeline Marques Marie Adeline Marques Laurent Monbrun Laurent Monbrun

subject

Lipopolysaccharides MESH: Signal Transduction MESH: Inflammation MESH : Toll-Like Receptor 4 Adipose tissue MESH : Adipocytes MESH : Lipopolysaccharides Mice chemistry.chemical_compound Fibrosis Adipocyte Adipocytes [ SDV.IMM ] Life Sciences [q-bio]/Immunology MESH: Obesity MESH: Animals lcsh:QH301-705.5 Mice Inbred C3H Toll-like receptor MESH : Diet High-Fat MESH: Toll-Like Receptor 4 3. Good health MESH: Insulin Resistance Adipose Tissue MESH: Fibrosis MESH : Fibrosis [SDV.IMM]Life Sciences [q-bio]/Immunology MESH : Obesity MESH : Insulin Resistance MESH: Adipose Tissue Signal Transduction medicine.medical_specialty [SDV.IMM] Life Sciences [q-bio]/Immunology Adipose tissue macrophages Biology Diet High-Fat MESH : Adipose Tissue General Biochemistry Genetics and Molecular Biology Immune system MESH : Mice Inbred C3H Internal medicine MESH : Mice medicine Animals Humans Obesity MESH: Mice Inbred C3H MESH: Mice MESH: Adipocytes Inflammation MESH : Signal Transduction MESH : Inflammation MESH: Humans MESH : Endotoxemia MESH : Humans 3T3-L1 medicine.disease Fibrosis MESH : Disease Models Animal Endotoxemia Toll-Like Receptor 4 Disease Models Animal MESH: Diet High-Fat Endocrinology lcsh:Biology (General)chemistry MESH: Endotoxemia MESH : Animals Insulin Resistance MESH: Disease Models Animal MESH: Lipopolysaccharides Adipocyte hypertrophy

description

International audience; 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.

year	journal	country	edition	language
2014-05-22	Cell Reports

https://doi.org/10.1016/j.celrep.2014.03.062