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.
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.
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 PPARγ (peroxisome proliferator-activated receptor γ) 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.
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.
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We gratefully acknowledge the valuable collaboration of all the Surgery Department for their technical support. This work was funded by the Instituto de Salud Carlos III (FIS PI061458 and FISPI06/90288) from the Spanish Ministerio de Sanidad y Consumo; and by Grants from the Department of Health (20/2005 and 4/2006) and Education of the Gobierno de Navarra, Spain. CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN) is an initiative of the Instituto de Salud Carlos III, Spain.
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Rodríguez, A., Gómez-Ambrosi, J., Catalán, V. et al. Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes. Int J Obes 33, 541–552 (2009). https://doi.org/10.1038/ijo.2009.40
- visceral adipocytes
- type 2 diabetes mellitus
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