Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity

Corneliu Henegar¹^,2 , Joan Tordjman¹^,2 , Vincent Achard¹^,2 , Danièle Lacasa¹^,2 , Isabelle Cremer¹^,2^,3 , Michèle Guerre-Millo¹^,2 , Christine Poitou¹^,2^,4 , Arnaud Basdevant¹^,2^,4 , Vladimir Stich⁵ , Nathalie Viguerie⁵^,6^,7^,8 , Dominique Langin⁵^,6^,7^,8 , Pierre Bedossa⁹^,10 , Jean-Daniel Zucker¹^,11 and Karine Clement¹^,2^,4

¹INSERM, UMR-S 872, Les Cordeliers, Eq. 7 Nutriomique and Eq. 13, Paris, F-75006 France

²Pierre et Marie Curie-Paris 6 University, Cordeliers Research Center, UMR-S 872, Paris, F-75006 France

³Paris Descartes University, UMR-S 872, Paris, F-75006 France

⁴Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié Salpêtrière Hospital, Nutrition and Endocrinology department, Paris, F-75013 France

⁵Franco-Czech Laboratory for Clinical Research on Obesity, INSERM and 3rd Faculty of Medicine, Charles University, Prague, CZ-10000, Czech Republic

⁶INSERM, U858, Obesity Research Laboratory, I2MR, Toulouse, F-31432 France

⁷Paul Sabatier University, Louis Bugnard Institute IFR31, Toulouse, F-31432 France

⁸Centre Hospitalier Universitaire de Toulouse, Toulouse, F-31059 France

⁹Assistance Publique-Hôpitaux de Paris (AP-HP), Beaujon Hospital, Pathology department, Clichy, F-92110 France

¹⁰CNRS, UMR 8149, Clichy, F-92110 France

¹¹IRD UR Géodes, Centre IRD de l'Ile de France, Bondy, F-93143 France

author email corresponding author email

Genome Biology 2008, 9:R14doi:10.1186/gb-2008-9-1-r14


Published:	21 January 2008

Subject areas: Bioinformatics, Cell biology, Physiology

Abstract

Background

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.

Results

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.

Conclusion

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.