NDT Advance Access published online on August 7, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp405
Human uraemic plasma stimulates release of leptin and uptake of tumour necrosis factor-
in visceral adipocytes
Division of Nephrology and Hypertension, University of California, Irvine, CA, USA
Correspondence and offprint requests to: Nosratola D. Vaziri; E-mail: ndvaziri{at}uci.edu
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Abstract |
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Background. End-stage renal disease (ESRD) is commonly associated with anorexia, malnutrition and inflammation. In addition to serving as the primary reservoir for energy storage, adipocytes produce numerous pro- and anti-inflammatory mediators and regulate food intake by releasing the appetite-suppressing (leptin) and appetite-stimulating (adiponectin) hormones. Under normal conditions, release of leptin is stimulated by feeding to prevent excess intake, and release of adiponectin is stimulated by fasting to induce feeding. However, under certain pathological conditions such as inflammation, maladaptive release of these hormones leads to anorexia, wasting and malnutrition and simultaneously intensifies inflammation. Anorexia, malnutrition and inflammation in ESRD are frequently accompanied by hyper-leptinaemia. This study was designed to test the hypothesis that uraemic plasma may stimulate leptin release and suppress adiponectin release in normal adipocytes.
Methods. Visceral adipose tissue was harvested from normal rats, and adipocytes were isolated and incubated for 2–4 h in media containing 90% plasma from 12 ESRD patients (before and after haemodialysis) and 12 normal control subjects.
Results. The ESRD group had a marked elevation of plasma TNF-
, IL-6, IL-8 and leptin concentrations before and after haemodialysis. Incubation in media containing plasma from the ESRD group elicited a much greater leptin release by adipocytes than that containing normal plasma. Post-dialysis plasma evoked an equally intense leptin release. The rise in leptin release was coupled with a parallel fall in TNF- concentration in the incubation media. In contrast to leptin, adiponectin release in the presence of uraemic plasma was similar to that found with the control plasma.
Conclusions. Exposure to uraemic plasma induces exuberant release of leptin that is coupled with avid uptake of TNF- by visceral adipocytes. These observations confirm the role of TNF-, formerly known as cachexin, in the over-production and release of leptin in patients with ESRD.
Keywords: adiponectin; anorexia; chronic kidney disease; inflammation; malnutrition
Received for publication: 30. 4.09
Accepted in revised form: 16. 7.09