Portal de investigación
Defective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis.
Fecha de publicación:
Fecha Ahead of Print:
Autores de CIPF
Participantes ajenos a CIPF
- Pellegrinelli V
- Figueroa-Juárez E
- Samuelson I
- U-Din M
- Rodriguez-Fdez S
- Virtue S
- Leggat J
- Çubuk C
- Peirce VJ
- Niemi T
- Campbell M
- Rodriguez-Cuenca S
- Blázquez JD
- Virtanen KA
Grupos de Investigación
Abstract
The relevance of extracellular matrix (ECM) remodeling is reported in white adipose tissue (AT) and obesity-related dysfunctions, but little is known about the importance of ECM remodeling in brown AT (BAT) function. Here, we show that a time course of high-fat diet (HFD) feeding progressively impairs diet-induced thermogenesis concomitantly with the development of fibro-inflammation in BAT. Higher markers of fibro-inflammation are associated with lower cold-induced BAT activity in humans. Similarly, when mice are housed at thermoneutrality, inactivated BAT features fibro-inflammation. We validate the pathophysiological relevance of BAT ECM remodeling in response to temperature challenges and HFD using a model of a primary defect in the collagen turnover mediated by partial ablation of the Pepd prolidase. Pepd-heterozygous mice display exacerbated dysfunction and BAT fibro-inflammation at thermoneutrality and in HFD. Our findings show the relevance of ECM remodeling in BAT activation and provide a mechanism for BAT dysfunction in obesity.
Datos de la publicación
- ISSN/ISSNe:
- 2211-1247, 2211-1247
- Tipo:
- Article
- Páginas:
- 112640-112640
- PubMed:
- 37318951
Cell Reports CELL PRESS
Citas Recibidas en Web of Science: 15
Documentos
- No hay documentos
Filiaciones
Keywords
- CP: Metabolism, PEPD, brown adipose tissue, extracellular matrix, fibrosis, obesity
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