Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity
1 INSERM, UMR-S 872, Les Cordeliers, Eq. 7 Nutriomique and Eq. 13, Paris, F-75006 France
2 Pierre et Marie Curie-Paris 6 University, Cordeliers Research Center, UMR-S 872, Paris, F-75006 France
3 Paris Descartes University, UMR-S 872, Paris, F-75006 France
4 Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Nutrition and Endocrinology department, Paris, F-75013 France
5 Franco-Czech Laboratory for Clinical Research on Obesity, INSERM and 3rd Faculty of Medicine, Charles University, Prague, CZ-10000, Czech Republic
6 INSERM, U858, Obesity Research Laboratory, I2MR, Toulouse, F-31432 France
7 Paul Sabatier University, Louis Bugnard Institute IFR31, Toulouse, F-31432 France
8 Centre Hospitalier Universitaire de Toulouse, Toulouse, F-31059 France
9 Assistance Publique-Hôpitaux de Paris (AP-HP), Beaujon Hospital, Pathology department, Clichy, F-92110 France
10 CNRS, UMR 8149, Clichy, F-92110 France
11 IRD UR Géodes, Centre IRD de l'Ile de France, Bondy, F-93143 France
Genome Biology 2008, 9:R14 doi:10.1186/gb-2008-9-1-r14Published: 21 January 2008
Investigations performed in mice and humans have acknowledged obesity as a low-grade inflammatory disease. Several molecular mechanisms have been convincingly shown to be 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.
Here, we analyzed the transcriptomic signature of the subcutaneous WAT in obese human subjects, in stable weight conditions and after weight loss following bariatric surgery. An original integrative functional genomics approach was applied to quantify relations between relevant structural and functional themes annotating differentially expressed genes in order 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 the integrin family, and suggested that these elements could play a major mediating role in a chain of interactions that connect 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 suggest that phenotypic alterations of human pre-adipocytes, induced by a pro-inflammatory environment, may lead to an excessive synthesis of ECM components.
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.