Potential Contribution of Adipose Tissue to Elevated Serum Cystatin C in Human Obesity
| Autor: | Jean-Philippe Bastard, Michèle Guerre-Millo, Karine Clément, Arnaud Basdevant, Marie-Christine Alessi, Soraya Fellahi, Nadia Naour, Anne Dutour, Christine Rouault, Jean-François Renucci, Christine Poitou |
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| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Subcutaneous Fat Gene Expression Medicine (miscellaneous) Renal function Adipose tissue urologic and male genital diseases chemistry.chemical_compound Endocrinology Blood serum Reference Values Internal medicine medicine Humans Obesity RNA Messenger Cystatin C reproductive and urinary physiology Cathepsin Creatinine Nutrition and Dietetics biology business.industry Cathepsins female genital diseases and pregnancy complications Adipose Tissue chemistry Case-Control Studies biology.protein Biomarker (medicine) Cystatin business Omentum |
| Zdroj: | Obesity. 17:2121-2126 |
| ISSN: | 1930-7381 |
| DOI: | 10.1038/oby.2009.96 |
| Popis: | Cystatin C, an endogenous inhibitor of cathepsin proteases has emerged as a biomarker of cardiovascular risk and reduced renal function. Epidemiological studies indicate that serum cystatin C increased in human obesity. Here, we evaluated the contribution of adipose tissue to this elevation, based on our previous observation that cystatin C is produced by in vitro differentiated human adipocytes. We measured serum cystatin C in 237 nonobese (age: 51 +/- 0.8 years; BMI: 22.8 +/- 0.11 kg/m(2)) and 248 obese subjects (age: 50 +/- 0.8 years; BMI: 34.7 +/- 0.29 kg/m(2)). Creatinine-based estimated glomerular filtration rate (eGFR) was calculated to account for renal status. Cystatin C gene expression and secretion were determined on surgical adipose tissue biopsies in a distinct group of subjects. Serum cystatin C is elevated in obese subjects of both genders, independently of reduced eGFR. Cystatin C mRNA is expressed in subcutaneous and omental adipose tissue, at twice higher levels in nonadipose than in adipose cells. Gene expression and cystatin C release by adipose tissue explants increase two- to threefold in obesity. These data confirm elevation of serum cystatin C in human obesity and strongly argue for a contribution of increased production of cystatin C by enlarged adipose tissue. Because cystatin C has the potential to affect adipose tissue and vascular homeostasis through local and/or systemic inhibition of cathepsins, this study adds a new factor to the list of adipose tissue secreted bioactive molecules implicated in obesity and obesity-linked complications. |
| Databáze: | OpenAIRE |
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