Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity.
Résumé
ABSTRACT: BACKGROUND: Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly involved in activating inflammatory processes and altering cell composition in white adipose tissue (WAT); however, the overall importance of these alterations, and their long-term impact on the metabolic functions of the WAT and on its morphology, remain unclear. RESULTS: Here, we analyzed the transcriptomic signature of the WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomic approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes, to construct a comprehensive map of transcriptional interactions defining the obese WAT. These analyses highlighted a significant up-regulation of genes and biological themes related to extracellular matrix (ECM) constituents, including members of integrins family, and suggested that these elements could play a major mediating role in a chain of interactions which connects local inflammatory phenomena to the alteration of WAT metabolic functions in obese subjects. Tissue and cellular investigations, driven by the analysis of transcriptional interactions, revealed an increased amount of interstitial fibrosis in obese WAT, associated with an infiltration of different types of inflammatory cells, and suggested that phenotypic alterations of human preadipocytes, induced by a proinflammatory environment, may lead to an excessive synthesis of ECM components. CONCLUSIONS: This study opens new perspectives in understanding the biology of human WAT and its pathologic changes indicative of tissue deterioration, associated with the development of obesity.
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