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- Title
Adiponectin receptor and adiponectin signaling in human tissue among patients with end-stage renal disease.
- Authors
Martinez Cantarin, Maria P.; Keith, Scott W.; Waldman, Scott A.; Falkner, Bonita
- Abstract
Background Adiponectin plasma levels in chronic kidney disease (CKD) are two to three times higher than in individuals with normal kidney function. Despite adiponectin's anti-diabetic, anti-inflammatory and anti-atherogenic properties, patients with CKD have insulin resistance, systemic inflammation and accelerated atherogenesis. Hence, although adiponectin production is increased by adipose tissue in end-stage renal disease (ESRD), it is unclear if its effects on metabolism remain intact. Methods To determine if there is adiponectin resistance in ESRD, we measured tissue levels of adiponectin receptor-1 (AdipoR1) and adiponectin downstream effectors in ESRD patients compared with normal kidney function controls. Blood and tissue samples were obtained from participants at the time of kidney transplantation or kidney donation. A follow-up blood sample was obtained 3–6 months after transplantation. Results AdipoR1 was higher in muscle and peripheral blood mononuclear cells collected from ESRD patients. There was also a nonsignificant increase in AdipoR1 in visceral fat of ESRD compared with controls. Compared with controls, phosphorylation of the adiponectin downstream effector adenosine monophosphate-activated protein kinase (AMPK) was higher in ESRD while acetyl-CoA carboxylase phosphorylation (ACC-P) and carnitine palmitoyl transferase-1 (CPT-1) levels were lower. In vitro, exposure of C2C12 cells to uremic serum resulted in upregulation of AdipoR1 and increased phosphorylation of AMPK but decreased ACC-P and CPT-1 expression. Conclusion Both our in vivo and in vitro observations indicate that uremia results in upregulation of AdipoR1 but adiponectin resistance at the post-receptor level.
- Subjects
ADIPONECTIN; HORMONE receptors; CELLULAR signal transduction; TISSUE physiology; CHRONIC kidney failure; THERAPEUTICS
- Publication
Nephrology Dialysis Transplantation, 2014, Vol 29, Issue 12, p2268
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfu249