Adipose tissue produces inflammation and immunity molecules suspected to be involved in obesity-related complications. The pattern of expression and the nutritional regulation of these molecules in humans are poorly understood. We analyzed the gene expression profiles of subcutaneous white adipose tissue from 29 obese subjects during very low calorie diet (VLCD) using cDNA microarray and reverse transcription quantitative PCR. The patterns of expression were compared with that of 17 non-obese subjects. We determined whether the regulated genes were expressed in adipocytes or stromavascular fraction cells. Gene expression profiling identified 100 inflammation-related transcripts that are regulated in obese individuals when eating a 28 day VLCD but not a 2 day VLCD. Cluster analysis showed that the pattern of gene expression in obese subjects after 28 day VLCD was closer to the profile of lean subjects than to the pattern of obese subjects before VLCD. Weight loss improves the inflammatory profile of obese subjects through a decrease of proinflammatory factors and an increase of anti-inflammatory molecules. The genes are expressed mostly in the stromavascular fraction of adipose tissue, which is shown to contain numerous macrophages. The beneficial effect of weight loss on obesity-related complications may be associated with the modification of the inflammatory profile in adipose tissue.

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.