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Human adipocyte function is impacted by mechanical cues
V Pellegrinelli1, J Heuvingh, O du Roure
1INSERM, UMR S 1166, Nutriomics Team, Paris, France; Sorbonne Universités, UPMC University of Paris 06, UMR S 1166, ICAN, Paris, France.
The Journal of Pathology
|March 14, 2014
Summary
Fibrosis in human white adipose tissue (WAT) impairs adipocyte function. Mechanical stress and fibrotic tissue in obesity negatively affect adipocyte lipolysis and inflammation via mechanosensitive pathways.
Area of Science:
- Adipose tissue biology
- Fibrosis research
- Obesity and metabolic disease
Background:
- Fibrosis is a key feature of white adipose tissue (WAT) in obesity-driven chronic inflammation.
- The functional consequences of increased interstitial fibrosis on adipocytes are not well understood.
Purpose of the Study:
- To investigate the impact of adipose tissue fibrosis on human adipocyte function in vitro.
- To explore the role of mechanical forces and mechanosensitive pathways in fibrotic adipocytes.
Main Methods:
- Development of a novel 3D in vitro culture system using human adipocytes and decellularized adipose tissue matrix (dMAT).
- Co-culture of adipocytes with dMAT in a peptide hydrogel, with and without mechanical compression.
- Analysis of adipocyte lipolysis, adipokine secretion, cytokine production, and fibrotic mediator expression.
- Investigation of CTGF promoter activity, β1-integrin/cytoskeleton pathways, and YAP/TEAD transcription factor involvement.
Main Results:
- Adipocytes cultured with dMAT exhibited reduced lipolysis and adipokine secretion.
- Increased expression of pro-inflammatory cytokines (IL-6, G-CSF) and fibrotic mediators (LOXL2, THSB2, CTGF) was observed.
- Mechanical compression of adipocyte cultures induced alterations in lipolytic activity and fibro-inflammation.
- CTGF expression correlated with peri-adipocyte fibrosis in obese individuals.
- dMAT-induced CTGF promoter activity was dependent on β1-integrin/cytoskeleton and YAP/TEAD pathways.
Conclusions:
- Fibrosis negatively impacts human adipocyte function through mechanosensitive molecules.
- Cell deformation and mechanical stress contribute to fibro-inflammation in adipose tissue.
- Targeting mechanosensitive pathways may offer therapeutic strategies for obesity-related adipose tissue dysfunction.
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