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

被引：104
作者：
Rodriguez, A. [2 ]
Gomez-Ambrosi, J. [2 ]
Catalan, V. [2 ]
Rotellar, F. [3 ]
Valenti, V. [3 ]
Silva, C. [1 ]
Mugueta, C. [4 ]
Pulido, M. R. [5 ]
Vazquez, R. [5 ]
Salvador, J. [1 ]
Malagon, M. M. [5 ]
Colina, I. [6 ]
Fruehbeck, G. [1 ,2 ]
机构：
[1] Univ Navarra Clin, Dept Endocrinol & Nutr, Pamplona 31008, Spain
[2] Univ Navarra Clin, Metab Res Lab, Pamplona 31008, Spain
[3] Univ Navarra Clin, Dept Surg, Pamplona 31008, Spain
[4] Univ Navarra Clin, Dept Biochem, Pamplona 31008, Spain
[5] Univ Cordoba, Dept Cell Biol Physiol & Immunol, IMIBIC, Cordoba, Spain
[6] Univ Navarra Clin, Dept Internal Med, Pamplona 31008, Spain
来源：
DIABETOLOGIA | 2012年 / 55卷 / 11期
关键词：
Apoptosis; Autophagy; Ghrelin; Obesity; Tumour necrosis factor alpha; Type; 2; diabetes; Visceral adipocytes; DES-ACYL GHRELIN; INSULIN-RESISTANCE; METABOLIC SYNDROME; DIABETES-MELLITUS; ADIPOSE-TISSUES; CELL-DEATH; GROWTH; HORMONE; OBESITY; EXPRESSION;
D O I：
10.1007/s00125-012-2671-5
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Proinflammatory and proapoptotic cytokines such as TNF-alpha are upregulated in human obesity. We evaluated the association between ghrelin isoforms (acylated and desacyl ghrelin) and TNF-alpha 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. Plasma concentrations of the ghrelin isoforms and TNF-alpha 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-alpha-induced apoptosis and autophagy-related molecules in omental adipocytes. Circulating concentrations of acylated ghrelin and TNF-alpha 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-alpha-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-alpha-induced increase of ATG5, BECN1 and ATG7 expression. Apoptosis and autophagy are upregulated in human visceral adipose tissue of patients with type 2 diabetes. Acylated and desacyl ghrelin reduce TNF-alpha-induced apoptosis and autophagy in human visceral adipocytes.
引用
收藏
页码：3038 / 3050
页数：13
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