Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: The adipogenesis master regulator PPAR-gamma (PPARg) is regulated by repressors such as NCoR. Systemic sclerosis (SSc) is associated with impaired PPARg expression and function and altered adipokine homeostasis. Loss of intradermal adipose tissue is prominent in the skin in SSc, as well as in mouse models of skin fibrosis.
Methods: To test the hypothesis that decreased adipose PPARg has a pathogenic role in dermal fibrosis and to ask whether rescuing its function might be beneficial, we characterized skin fibrosis in mice with adipocyte-specific NCoR ablation using the bleomycin model.
Adipocyte-NCoR null mice on a high-fat diet showed PPARg activation, enhanced insulin sensitivity and alterations in serum adipokines. Moreover, NCoR null mice were resistant to bleomycin-induced changes in adipocyte size and function and loss of intradermal adipose tissue. Importantly, NCoR null mice had attenuated skin fibrosis measured both histologically and biochemically, which was reversed by the pharmacological inhibitor of PPARg GW9662. Taken together, these findings suggest that enhanced dermal adipogenesis mediated by tissue-specific PPARg activation modulates skin fibrosis.
Conclusion: These results strongly suggest that intradermal adipose plays an active role in skin fibrosis. Targeting adipogenesis might therefore represent an innovative approach to control skin fibrosis in SSc
To cite this abstract in AMA style:Korman B, Goncalves Marangoni R, Tourtellotte W, Varga J. Adipose Loss of Co-Repressor Ncor Attenuates Bleomycin-Induced Skin Fibrosis By Enhancing PPAR-Gamma Signaling [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/adipose-loss-of-co-repressor-ncor-attenuates-bleomycin-induced-skin-fibrosis-by-enhancing-ppar-gamma-signaling/. Accessed December 16, 2017.
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ACR Meeting Abstracts - http://acrabstracts.org/abstract/adipose-loss-of-co-repressor-ncor-attenuates-bleomycin-induced-skin-fibrosis-by-enhancing-ppar-gamma-signaling/