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Diabetologia
Published in: Diabetologia 11/2012

01-11-2012 | Article

The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes

Authors: A. Rodríguez, J. Gómez-Ambrosi, V. Catalán, F. Rotellar, V. Valentí, C. Silva, C. Mugueta, M. R. Pulido, R. Vázquez, J. Salvador, M. M. Malagón, I. Colina, G. Frühbeck

Published in: Diabetologia | Issue 11/2012

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Abstract

Aims/hypothesis

Proinflammatory and proapoptotic cytokines such as TNF-α are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-α in obesity and obesity-associated type 2 diabetes, as well as the potential role of ghrelin in the control of apoptosis and autophagy in human adipocytes.

Methods

Plasma concentrations of the ghrelin isoforms and TNF-α were measured in 194 participants. Ghrelin and ghrelin O-acyltransferase (GOAT) levels were analysed by western-blot, immunohistochemistry and real-time PCR in 53 biopsies of human omental adipose tissue. We also determined the effect of acylated and desacyl ghrelin (10 to 1,000 pmol/l) on TNF-α-induced apoptosis and autophagy-related molecules in omental adipocytes.

Results

Circulating concentrations of acylated ghrelin and TNF-α were increased, whereas desacyl ghrelin levels were decreased in obesity-associated type 2 diabetes. Ghrelin and GOAT were produced in omental and subcutaneous adipose tissue. Visceral adipose tissue from obese patients with type 2 diabetes showed higher levels of GOAT, increased adipocyte apoptosis and increased expression of the autophagy-related genes ATG5, BECN1 and ATG7. In differentiating human omental adipocytes, incubation with acylated and desacyl ghrelin reduced TNF-α-induced activation of caspase-8 and caspase-3, and cell death. In addition, acylated ghrelin reduced the basal expression of the autophagy-related genes ATG5 and ATG7, while desacyl ghrelin inhibited the TNF-α-induced increase of ATG5, BECN1 and ATG7 expression.

Conclusions/interpretation

Apoptosis and autophagy are upregulated in human visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl ghrelin reduce TNF-α-induced apoptosis and autophagy in human visceral adipocytes.
Appendix
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Metadata
Title
The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes
Authors
A. Rodríguez
J. Gómez-Ambrosi
V. Catalán
F. Rotellar
V. Valentí
C. Silva
C. Mugueta
M. R. Pulido
R. Vázquez
J. Salvador
M. M. Malagón
I. Colina
G. Frühbeck
Publication date
01-11-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 11/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2671-5

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