26 research outputs found
Loss of the co-repressor GPS2 sensitizes macrophage activation upon metabolic stress induced by obesity and type 2 diabetes
International audienceHumans with obesity differ in their susceptibility to developing insulin resistance and type 2 diabetes (T2D). This variation may relate to the extent of adipose tissue (AT) inflammation that develops as their obesity progresses. The state of macrophage activation has a central role in determining the degree of AT inflammation and thus its dysfunction, and these states are driven by epigenomic alterations linked to gene expression. The underlying mechanisms that regulate these alterations, however, are poorly defined. Here we demonstrate that a co-repressor complex containing G protein pathway suppressor 2 (GPS2) crucially controls the macrophage epigenome during activation by metabolic stress. The study of AT from humans with and without obesity revealed correlations between reduced GPS2 expression in macrophages, elevated systemic and AT inflammation, and diabetic status. The causality of this relationship was confirmed by using macrophage-specific Gps2-knockout (KO) mice, in which inappropriate co-repressor complex function caused enhancer activation, pro-inflammatory gene expression and hypersensitivity toward metabolic-stress signals. By contrast, transplantation of GPS2-overexpressing bone marrow into two mouse models of obesity (ob/ob and diet-induced obesity) reduced inflammation and improved insulin sensitivity. Thus, our data reveal a potentially reversible disease mechanism that links co-repressor-dependent epigenomic alterations in macrophages to AT inflammation and the development of T2D
Comparação dos resultados da fala após as cirurgias de retalho farÃngeo e veloplastia intravelar para correção da disfunção velofarÃngea Comparison of speech results following pharyngeal flap and intravelar veloplasty for correction of velopharyngeal dysfunction
OBJETIVO: Comparar a fala e o funcionamento velofarÃngeo após as técnicas de retalho farÃngeo e veloplastia intravelar para a correção da disfunção velofarÃngea residual. MÉTODOS: Foi realizado um estudo retrospectivo com análise de 148 casos com fissura labiopalatina operada e submetidos à correção cirúrgica da disfunção velofarÃngea, sendo 77 com retalho farÃngeo (média de idade: 20,4 anos) e 71 com veloplastia intravelar (média de idade: 16,2 anos). Foram avaliadas a ressonância da fala, a presença de articulações compensatórias, a emissão de ar nasal e a extensão da falha no fechamento velofarÃngeo antes e após as duas técnicas. RESULTADOS: Dos 77 casos submetidos ao retalho farÃngeo 64 (83%) apresentaram melhora na ressonância, enquanto que dos 71 casos com veloplastia intravelar 48 (68%) revelaram melhora, havendo diferença significativa entre os grupos. No grupo com retalho farÃngeo, seis (8%) apresentaram melhora na articulação compensatória e dois (3%) no grupo veloplastia intravelar, enquanto a emissão de ar nasal melhorou em 17 (22%) casos com retalho farÃngeo e em 18 (26%) com veloplastia intravelar. Não houve diferença entre os grupos quanto à articulação compensatória e emissão de ar nasal. A falha no fechamento velofarÃngeo reduziu em 75 (96%) casos com retalho farÃngeo e 46 (66%) com a veloplastia intravelar, havendo diferença entre os grupos. CONCLUSÃO: A técnica de retalho farÃngeo mostrou-se mais efetiva na melhora da ressonância e no fechamento velofarÃngeo quando comparada à veloplastia intravelar.<br>PURPOSE: To compare speech and velopharyngeal function after pharyngeal flap and intravelar veloplasty techniques for the correction of residual velopharyngeal dysfunction. METHODS: It was carried out a retrospective study analyzing 148 cases of cleft lip and palate operated and submitted to velopharyngeal dysfunction surgical correction, 77 with pharyngeal flap (mean age: 20.4 years) and 71 with intravelar veloplasty (mean age: 16.2 years). Speech resonance, presence of compensatory articulations, nasal air emission, and velopharyngeal gap size were assessed before and after the use of both techniques. RESULTS: Sixty four (83%) of the 77 cases submitted to pharyngeal flap presented resonance improvement, while 48 (68%) of the 71 cases with intravelar veloplasty improved, with significant difference between the groups. Six (8%) subjects with pharyngeal flap, and two (3%) with intravelar veloplasty showed improvement in compensatory articulations, while nasal air emission improved in 17 (22%) cases with pharyngeal flap, and 18 (26%) with intravelar veloplasty. No significant differences were found between the groups regarding compensatory articulations and nasal air emission. The velopharyngeal gap size reduced in 75 (96%) cases with pharyngeal flap, and 46 (66%) with intravelar veloplasty, with a significant difference between the groups. CONCLUSION: The pharyngeal flap technique was more effective in improving resonance and velopharyngeal closure, when compared to intravelar veloplasty