Equine Adiponectin Receptor 1

Resume

Background

Plasma levels of adiponectin in chronic kidney disease (CKD) are two to three times higher than in individuals with normal kidney function. Despite adiponectin’s antidiabetic, anti-inflammatory, and antiatherogenic properties, CKD patients present with insulin resistance, systemic inflammation, and accelerated atherogenesis. Thus, although adipose tissue increases adiponectin production in end-stage renal disease (ESRD), it is unclear whether its effects on metabolism remain intact.

Methods

To determine whether there is resistance to adiponectin in ESRD, we measured tissue levels of adiponectin receptor-1 (AdipoR1) and adiponectin post-effectors in ESRD patients compared to controls of normal kidney function. Blood and tissue samples were obtained from the 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 non-significant increase of AdipoR1 in ESRD visceral fat compared to controls. Compared with controls, adiponectin down-effector adenosine monophosphate (AMPK) activated protein kinase phosphorylation was higher in ESRD, while acetyl-CoA carboxylase (ACC-P) and carnitine palmitoyltransferase phosphorylation levels -1 (CPT-1) were lower. In vitro, exposure of C2C12 cells to uremic serum resulted in upregulation of AdipoR1 and increased phosphorylation of AMPK, but decreased expression of ACC-P and CPT-1.

Conclusion

Both our in vivo and in vitro observations indicate that uremia results in upregulation of AdipoR1 but resistance to adiponectin at the post-receptor level.

Keywords

adiponectin, cell signaling, ESRD, inflammation

Topic:

signal transduction renal function renal failure, chronic carnitine o-palmitoyltransferase phosphorylation, adiponectinampk, peripheral blood mononuclear cell receptors, adiponectin

Thematic section: Chronic kidney disease

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