Human adipocyte function is impacted by mechanical cues

Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipo...

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Bibliographic Details
Published in:The Journal of pathology 2014-06, Vol.233 (2), p.183-195
Main Authors: Pellegrinelli, V, Heuvingh, J, du Roure, O, Rouault, C, Devulder, A, Klein, C, Lacasa, M, Clément, E, Lacasa, D, Clément, K
Format: Article
Language:English
Subjects:
3D culture
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Adipocytes
Adipocytes, White - metabolism
Adipocytes, White - pathology
Adipokines - genetics
Adipokines - metabolism
Amino Acid Oxidoreductases - genetics
Amino Acid Oxidoreductases - metabolism
Binding Sites
Cell Shape
Cells, Cultured
Collagen - metabolism
Connective Tissue Growth Factor - genetics
Connective Tissue Growth Factor - metabolism
Fibrosis
Gene Expression Regulation
Granulocyte Colony-Stimulating Factor - genetics
Granulocyte Colony-Stimulating Factor - metabolism
human obesity
Humans
Hydrogels
Integrin beta1 - genetics
Integrin beta1 - metabolism
Interleukin-6 - genetics
Interleukin-6 - metabolism
Lipolysis
Mechanotransduction, Cellular
Obesity - genetics
Obesity - metabolism
Obesity - pathology
Obesity - physiopathology
Phosphoproteins - genetics
Phosphoproteins - metabolism
Promoter Regions, Genetic
Rodents
Time Factors
Transcription Factors
Transfection
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Summary:Fibrosis is a hallmark of human white adipose tissue (WAT) during obesity‐induced chronic inflammation. The functional impact of increased interstitial fibrosis (peri‐adipocyte fibrosis) on adjacent adipocytes remains unknown. Here we developed a novel in vitro 3D culture system in which human adipocytes and decellularized material of adipose tissue (dMAT) from obese subjects are embedded in a peptide hydrogel. When cultured with dMAT, adipocytes showed decreased lipolysis and adipokine secretion and increased expression/production of cytokines (IL‐6, G‐CSF) and fibrotic mediators (LOXL2 and the matricellular proteins THSB2 and CTGF). Moreover, some alterations including lipolytic activity and fibro‐inflammation also occurred when the adipocyte/hydrogel culture was mechanically compressed. Notably, CTGF expression levels correlated with the amount of peri‐adipocyte fibrosis in WAT from obese individuals. Moreover, dMAT‐dependent CTGF promoter activity, which depends on β1‐integrin/cytoskeleton pathways, was enhanced in the presence of YAP, a mechanosensitive co‐activator of TEAD transcription factors. Mutation of TEAD binding sites abolished the dMAT‐induced promoter activity. In conclusion, fibrosis may negatively affect human adipocyte function via mechanosensitive molecules, in part stimulated by cell deformation. Published by John Wiley & Sons, Ltd
ISSN:0022-3417
1096-9896
DOI:10.1002/path.4347