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Cathepsin S, a novel biomarker of adiposity: relevance to atherogenesis
Abstract
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‐lβ, and tumor necrosis factor‐α 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.
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“Among the genes showing the strongest association with the BMI were cathepsin S (CTSS), involved in the degradation of several components of the extracellular matrix [19], lymphocyte cytosolic protein 2 (LCP2) and CD247 (CD247), both related to T cell development and activation, as well as the hypoxia-inducible factor 1 (HIF1A).”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [19]
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Metadata
- Authors
- Taleb, S., Lacasa, D., Bastard, J., Poitou, C., Cancello, R., Pelloux, V., Viguerie, N., Benis, A., Zucker, J., Bouillot, J., Coussieu, C., Basdevant, A., Langin, D., & Clement, K.
- Affiliations
- Inserm (FR)
- INSERM “Avenir” Team and CHRU Pitié Salpétrière Hôtel‐Dieu Nutrition Department Centre de Recherche en Nutrition Humaine F‐75004 Paris
- Hôtel-Dieu de Paris (FR)
- Pitié-Salpêtrière Hospital (FR)
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-06-28
- Volume
- 19
- Issue
- 11
- Pages
- 1540-1542
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2165745035
- Cited by
- 158
- References
- 42
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 6 · 2019: 4 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 10 · 2013: 9 · 2012: 13
- FWCI
- 8.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Keywords
- cathepsin S, adiposity biomarkers, obesity, atherosclerosis, subcutaneous adipose tissue, gene expression profiling, body mass index, cysteine protease, inflammation, lipopolysaccharide, IL-1β, TNF-α, plasma triglycerides, cardiovascular risk
- MeSH terms
- Adipose Tissue, Cathepsins, Female, Humans, Muscle, Smooth, Vascular, Obesity, RNA, Messenger, Biomarkers, Extracellular Matrix Proteins, Adipocytes, Gene Expression Profiling, Adiposity, Atherosclerosis
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