02229nas a2200325   4500008004100000022001400041245014800055210006900203260001600272300001100288490000700299520106600306100002701372700003201399700002401431700001701455700002601472700001901498700002101517700001801538700002201556700001701578700001901595700002901614700002001643700002301663700002301686700002401709856017001733       2023                        eng d  a2211-124700aDefective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis.0 aDefective extracellular matrix remodeling in brown adipose tissu  c2023 Jun 13  a1126400 v423 a<p>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.</p>1 aPellegrinelli, Vanessa1 aFigueroa-Juárez, Elizabeth1 aSamuelson, Isabella1 aU-Din, Mueez1 aRodriguez-Fdez, Sonia1 aVirtue, Samuel1 aLeggat, Jennifer1 aCubuk, Cankut1 aPeirce, Vivian, J1 aNiemi, Tarja1 aCampbell, Mark1 aRodriguez-Cuenca, Sergio1 aDopazo, Joaquin1 aCarobbio, Stefania1 aVirtanen, Kirsi, A1 aVidal-Puig, Antonio  uhttp://clinbioinfosspa.es/content/defective-extracellular-matrix-remodeling-brown-adipose-tissue-associated-fibro-inflammation-and-reduced-diet-induced-thermogenesis