Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

• Published in: International Journal of Obesity 2009-05, Vol.33 (5), p.541-552
• Main Authors: Rodriguez, A, Gomez-Ambrosi, J, Catalan, V, Gil, M.J, Becerril, S, Sainz, N, Silva, C, Salvador, J, Colina, I, Fruhbeck, G
• Format: Article
• Language: English
• Subjects: Accumulation; Acetylation; acylation; Adipocytes; Adipocytes - metabolism; Adipogenesis - drug effects; Adipose tissue; Aged; anthropometric measurements; Biological and medical sciences; Body fat; Body Mass Index; desacyl ghrelin; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology; Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fat cells; Fatty acids; Female; Ghrelin; Ghrelin - blood; Ghrelin - pharmacology; Glucose; Growth hormones; Health Promotion and Disease Prevention; Homeostasis; Humans; Incubation; Insulin; Insulin - blood; Insulin resistance; Internal Medicine; Intra-Abdominal Fat - metabolism; Lipid metabolism; Lipids; Lipids - biosynthesis; lipogenesis; Male; Medical sciences; Medicine; Medicine & Public Health; men; Metabolic Diseases; Middle Aged; noninsulin-dependent diabetes mellitus; Obesity; Obesity - complications; Obesity - metabolism; omentum; original-article; Peptides; Physiological aspects; PPAR gamma - metabolism; protein synthesis; Proteins; Public Health; Receptors, Ghrelin - metabolism; Spain; Sterol Regulatory Element Binding Protein 1 - metabolism; Sterols; visceral fat; Waist Circumference; women
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2009.40

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 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. 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.