Adiponutrin: A multimeric plasma protein

https://doi.org/10.1016/j.bbrc.2014.03.078Get rights and content
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Highlights

  • Human adiponutrin is present in plasma as disulfide bond-dependent multimers.

  • Human plasma adiponutrin circulates in the low nM range, estimated to 1.25–4 nM.

  • Adiponutrin is secreted by HepG2 cells in the presence of oleate.

Abstract

The interest in adiponutrin stems from adiponutrin variant I148M, which is strongly associated to non-alcoholic fatty liver disease. Adiponutrin has to date been considered to be solely an intracellular protein, with a role in lipid metabolism in liver and adipose tissue. However, a physiologically relevant role for adiponutrin has not been found. The aim of this study was to investigate the presence of adiponutrin in human plasma, a new facet of adiponutrin research. We demonstrate that adiponutrin is present in plasma as disulfide-bond dependent multimers, estimated to circulate at a concentration of 1.25–4 nM. Experiments reveal that adiponutrin is released from HepG2 cells in the presence of oleate. The presence of adiponutrin in plasma makes it accessible for clinical investigations and use as a potential biomarker for metabolic disease.

Abbreviations

PNPLA
patatin-like phospholipase domain-containing protein
ADPN
adiponutrin
LPAAT
lysophosphatidic acid acyltransferaese
VLDL
very low density lipoprotein
ApoB100
Apolipoprotein B100
PPD
Plasma Proteome Database
CBS
Center of Biological Sequence Analysis
DTU
Technical University of Denmark
HUVEC
human umbilical vein endothelial cells
DDM
n-dodecyl-β-d-maltoside
DIG
Digitonin
MTTP
microsomal triglyceride transfer protein

Keywords

Adiponutrin
ADPN
PNPLA3
HepG2 cells
Steatosis
NAFLD

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