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The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes
dc.contributor.author | Rodríguez, A | |
dc.contributor.author | Gómez-Ambrosi, Javier | |
dc.contributor.author | Catalán, Victoria | |
dc.contributor.author | Rotellar, Fernando | |
dc.contributor.author | Valentí, Víctor | |
dc.contributor.author | Silva, Camilo | |
dc.contributor.author | Mugueta, C. | |
dc.contributor.author | Pulido, Marina R. | |
dc.contributor.author | Vázquez, R. | |
dc.contributor.author | Salvador, Javier | |
dc.contributor.author | Malagón, María M. | |
dc.contributor.author | Colina, I. | |
dc.contributor.author | Frühbeck, Gema | |
dc.date.accessioned | 2024-01-26T13:21:06Z | |
dc.date.available | 2024-01-26T13:21:06Z | |
dc.date.issued | 2012 | |
dc.identifier.issn | 1432-0428 | |
dc.identifier.uri | http://hdl.handle.net/10396/26803 | |
dc.description.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. | es_ES |
dc.format.mimetype | application/pdf | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | SpringerLink | es_ES |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/4.0/ | es_ES |
dc.source | Rodríguez, A., Gómez-Ambrosi, J., Catalán, V. et al. The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes. Diabetologia 55, 3038–3050 (2012) | es_ES |
dc.subject | Apoptosis | es_ES |
dc.subject | Autophagy | es_ES |
dc.subject | Ghrelin | es_ES |
dc.subject | Obesity | es_ES |
dc.subject | Tumour necrosis factor α | es_ES |
dc.subject | Type 2 diabetes | es_ES |
dc.subject | Visceral adipocytes | es_ES |
dc.title | The ghrelin O-acyltransferase–ghrelin system reduces TNF-α-induced apoptosis and autophagy in human visceral adipocytes | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | https://doi.org/10.1007/s00125-012-2671-5 | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |