PUBLICAÇÕES científicas

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

Rodríguez A, Gómez-Ambrosi J, Catalán V, Rotellar F, Valentí V, Silva C [ES], Mugueta C [ES], Pulido MR, Vázquez R, Salvador J, Malagón MM, Colina I [ES], Frühbeck G.
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.

Revisão:Diabetologia

Data: 7/Ago/2012

Cirurgia Geral e Digestiva Bioquímica Clínica [ES] Endocrinologia e Nutrição [ES] Unidade de Check-Up Área de Obesidade

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.

CITAÇÃO DO ARTIGO  2012 Aug 7

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