Acylated and desacyl ghrelin stimulate lipid accumulation in human visceral adipocytes

Int J Obes (Lond). 2009 May;33(5):541-52. doi: 10.1038/ijo.2009.40. Epub 2009 Feb 24.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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