Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes.

Abstract

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 PPARgamma (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.

• Authors: A Rodríguez, J Gómez-Ambrosi, V Catalán, M J Gil, S Becerril, N Sáinz, C Silva, J Salvador, I Colina, G Frühbeck
• Journal: International journal of obesity (2005) (Int J Obes (Lond)) Vol. 33 Issue 5 Pg. 541-52 (May 2009) ISSN: 1476-5497 [Electronic] England
• PMID: 19238155 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ghrelin
• Insulin
• Lipids
• PPAR gamma
• Receptors, Ghrelin
• Sterol Regulatory Element Binding Protein 1
• ghrelin, des-n-octanoyl

Topics

• Acetylation
• Adipocytes (metabolism)
• Adipogenesis (drug effects)
• Aged
• Body Mass Index
• Diabetes Mellitus, Type 2 (complications, metabolism)
• Female
• Ghrelin (blood, pharmacology)
• Humans
• Insulin (blood)
• Intra-Abdominal Fat (metabolism)
• Lipids (biosynthesis)
• Male
• Middle Aged
• Obesity (complications, metabolism)
• PPAR gamma (metabolism)
• Receptors, Ghrelin (metabolism)
• Spain
• Sterol Regulatory Element Binding Protein 1 (metabolism)
• Waist Circumference