Key result
Defective extracellular matrix remodeling in brown adipose tissue, mediated by Pepd prolidase ablation or high-fat diet, exacerbates fibro-inflammation and impairs thermogenesis.
Why the study?
While extracellular matrix remodeling is known to play a role in white adipose tissue and obesity-related dysfunctions, its importance in brown adipose tissue function remains poorly understood.
Extracellular matrix remodeling is crucial for brown adipose tissue activation, and its defect provides a mechanism for BAT dysfunction in obesity.
Defective ECM remodeling may impair BAT function in obese models; leaves open relevance to human thermogenic therapies.
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.
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Pellegrinelli et al. (2023) studied Obesity and brown adipose tissue dysfunction. High-fat diet and defective ECM remodeling (Pepd prolidase ablation) was evaluated on Diet-induced thermogenesis and fibro-inflammation in brown adipose tissue. Defective extracellular matrix remodeling in brown adipose tissue, mediated by Pepd prolidase ablation or high-fat diet, exacerbates fibro-inflammation and impairs thermogenesis.
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