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


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.
Henegar
Corneliu
C
INSERM, UMR-S 872, Les Cordeliers, Eq, 7 Nutriomique and Eq, 13, Paris, F-75006 France. corneliu@henegar.info
Tordjman
Joan
J
Achard
Vincent
V
Lacasa
Danièle
D
Cremer
Isabelle
I
Guerre-Millo
Michèle
M
Poitou
Christine
C
Basdevant
Arnaud
A
Stich
Vladimir
V
Viguerie
Nathalie
N
Langin
Dominique
D
Bedossa
Pierre
P
Zucker
Jean-Daniel
JD
Clement
Karine
K
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D052436:Adipose Tissue, White / Q000378:metabolism / Q000473:pathology; D050110:Bariatric Surgery; D005109:Extracellular Matrix / Q000473:pathology*; D005355:Fibrosis; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D015431:Weight Loss