Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

被引：168

作者：

Rodriguez, A. ^{[2
]}

Gomez-Ambrosi, J. ^{[2
]}

Catalan, V. ^{[2
]}

Gil, M. J. ^{[3
]}

Becerril, S. ^{[2
]}

Sainz, N. ^{[2
]}

Silva, C. ^{[1
]}

Salvador, J. ^{[1
]}

Colina, I. ^{[4
]}

Fruehbeck, G. ^{[1
,2
]}

机构：

[1] Univ Navarra, Univ Navarra Clin, Dept Endocrinol, Pamplona 31008, Spain

[2] Univ Navarra, Univ Navarra Clin, Metab Res Lab, Pamplona 31008, Spain

[3] Univ Navarra, Univ Navarra Clin, Dept Biochem, Pamplona 31008, Spain

[4] Univ Navarra, Univ Navarra Clin, Dept Internal Med, Pamplona 31008, Spain

来源：

INTERNATIONAL JOURNAL OF OBESITY | 2009年 / 33卷 / 05期

关键词：

ghrelin; adipogenesis; visceral adipocytes; type 2 diabetes mellitus; HORMONE SECRETAGOGUE RECEPTOR; TYPE-2; DIABETES-MELLITUS; INSULIN-RESISTANCE; PLASMA-LEVELS; NONACYLATED GHRELIN; METABOLIC SYNDROME; OREXIGENIC ACTION; ACTIVE GHRELIN; ADIPOSE-TISSUE; OBESE CHILDREN;

D O I：

10.1038/ijo.2009.40

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives: The orexigenic hormone ghrelin circulates mainly in two forms, acylated and desacyl ghrelin. We evaluated the impact of obesity and obesity-associated type 2 diabetes (T2D) on ghrelin forms and the potential role of acylated and desacyl ghrelin in the control of adipogenesis in humans. Methods: Plasma concentrations of the different ghrelin forms were measured in 80 subjects. The expression of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) was analyzed in omental adipose tissue using western blot and immunohistochemistry, and the effect of acylated ghrelin and desacyl ghrelin (0.1-1000 pmol l(-1)) on adipogenesis was determined in vitro in omental adipocytes. Results: Circulating concentrations of acylated ghrelin were increased, whereas desacyl ghrelin levels were decreased, in obesity and obesity-associated T2D. Body mass index, waist circumference, insulin and HOMA (homeostasis model assessment) index were positively correlated with acylated ghrelin levels. Obese individuals showed a lower protein expression of GHS-R in omental adipose tissue. In differentiating omental adipocytes, incubation with both acylated and desacyl ghrelin significantly increased PPAR gamma (peroxisome proliferator-activated receptor gamma) and SREBP1 (sterol-regulatory element binding protein-1) mRNA levels, as well as several fat storage-related proteins, including acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase and perilipin. Consequently, both the ghrelin forms stimulated intracytoplasmatic lipid accumulation. Conclusions: Both acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Given the lipogenic effect of acylated ghrelin on visceral adipocytes, the herein-reported elevation of its circulating concentrations in obese individuals may play a role in excessive fat accumulation in obesity. International Journal of Obesity (2009) 33, 541-552; doi:10.1038/ijo.2009.40; published online 24 February 2009

引用

页码：541 / 552

页数：12

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