Potential contribution of adipose tissue to elevated serum cystatin C in human obesity.
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.
Naour
Nadia
N
INSERM, U872, Paris, France.
Fellahi
Soraya
S
Renucci
Jean-François
JF
Poitou
Christine
C
Rouault
Christine
C
Basdevant
Arnaud
A
Dutour
Anne
A
Alessi
Marie-Christine
MC
Bastard
Jean-Philippe
JP
Clément
Karine
K
Guerre-Millo
Michèle
M
D000273:Adipose Tissue / Q000378:metabolism*; D016022:Case-Control Studies; D002403:Cathepsins / Q000037:antagonists & inhibitors; D055316:Cystatin C / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009765:Obesity / Q000097:blood* / Q000378:metabolism; D009852:Omentum / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D050151:Subcutaneous Fat / Q000378:metabolism
D055316:Cystatin C; D012333:RNA, Messenger; D002403:Cathepsins