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.

Links

Publisher Full Text

Authors

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

Institution

Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.

Source

Diabetologia 55:11 2012 Nov pg 3038-50

MeSH

Acylation
Acyltransferases
Apoptosis
Autophagy
Cells, Cultured
Diabetes Mellitus, Type 2
Female
Ghrelin
Humans
Intra-Abdominal Fat
Male
Middle Aged
Obesity
Omentum
RNA, Messenger
Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22869322