Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis.
The molecular mechanisms by which obesity increases the risk of cardiovascular diseases are poorly understood. The purpose of this study was to identify candidate biomarkers overexpressed in adipose tissue of obese subjects that could link expanded fat mass to atherosclerosis. We compared gene expression profile in subcutaneous adipose tissue (scWAT) of 28 obese and 11 lean subjects using microarray technology. This analysis identified 240 genes significantly overexpressed in scWAT of obese subjects. The genes were then ranked according to the correlation between gene expression and body mass index (BMI). In this list, the elastolytic cysteine protease cathepsin S was among the highly correlated genes. RT-PCR and Western blotting confirmed the increase in cathepsin S mRNA (P=0.006) and protein (P<0.05) in obese scWAT. The circulating concentrations of cathepsin S were also significantly higher in obese than in nonobese subjects (P<0.0001). Both cathepsin S mRNA in scWAT and circulating levels were positively correlated with BMI, body fat, and plasma triglyceride levels. In addition, we show that the proinflammatory factors, lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha increase cathepsin S secretion in human scWAT explants. This study identifies cathepsin S as a novel marker of adiposity. Since this enzyme has been implicated in the development of atherosclerotic lesions, we propose that cathepsin S represents a molecular link between obesity and atherosclerosis.
INSERM Avenir, Paris, France.
Soraya
S
Taleb
Danièle
D
Lacasa
Jean-Philippe
JP
Bastard
Christine
C
Poitou
Raffaella
R
Cancello
Veronique
V
Pelloux
Nathalie
N
Viguerie
Arriel
A
Benis
Jean-Daniel
JD
Zucker
Jean-Luc
JL
Bouillot
Christiane
C
Coussieu
Arnaud
A
Basdevant
Dominique
D
Langin
Karine
K
Clement
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D050197:Atherosclerosis / Q000209:etiology*; D015415:Biomarkers; D002403:Cathepsins / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D009765:Obesity / Q000150:complications / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis
D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D002403:Cathepsins; C028217:cathepsin S