Molecular Biology

Gastric ghrelin cells in obese patients are hyperactive

Abstract

Background/objectives

Distribution and activity of ghrelin cells in the stomach of obese subjects are controversial.

Subjects/methods

We examined samples from stomachs removed by sleeve gastrectomy in 49 obese subjects (normoglycemic, hyperglycemic and diabetic) and quantified the density of ghrelin/chromogranin endocrine cells by immunohistochemistry. Data were compared with those from 13 lean subjects evaluated by gastroscopy. In 44 cases (11 controls and 33 obese patients) a gene expression analysis of ghrelin and its activating enzyme ghrelin O-acyl transferase (GOAT) was performed. In 21 cases (4 controls and 17 obese patients) the protein levels of unacylated and acylated-ghrelin were measured by ELISA tests. In 18 cases (4 controls and 14 obese patients) the morphology of ghrelin-producing cells was evaluated by electron microscopy.

Results

The obese group, either considered as total population or divided into subgroups, did not show any significant difference in ghrelin cell density when compared with control subjects. Inter-glandular smooth muscle fibres were increased in obese patients. In line with a positive trend of the desacylated form found by ELISA, Ghrelin and GOAT mRNA expression in obese patients was significantly increased. The unique ghrelin cell ultrastructure was maintained in all obese groups. In the hyperglycemic obese patients, the higher ghrelin expression matched with ultrastructural signs of endocrine hyperactivity, including expanded rough endoplasmic reticulum and reduced density, size and electron-density of endocrine granules. A positive correlation between ghrelin gene expression and glycemic values, body mass index and GOAT was also found. All obese patients with type 2 diabetes recovered from diabetes at follow-up after 5 months with a 16.5% of weight loss.

Conclusions

Given the known inhibitory role on insulin secretion of ghrelin, these results suggest a possible role for gastric ghrelin overproduction in the complex architecture that takes part in the pathogenesis of type 2 diabetes.

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Fig. 1: Density of ghrelin-producing cells (GPCs) in human stomach.
Fig. 2: Gene expression of ghrelin and its activator ghrelin O-acyltransferase in human stomach.
Fig. 3: Representative electron microscope images showing ghrelin-like cells of obese and control patients.
Fig. 4: Morphometric analysis performed on electron microscope images of ghrelin cells in obese and control groups.
Fig. 5: Correlation between glycaemic values and ghrelin gene expression in obese patients.

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Acknowledgements

We thank Prof Filippo Palermo (Catania) and Prof Daniela Morale (Milano) for their assistance in evaluating the statistical data, Dr Giuseppe Grasso (Catania), Dr Valentina Merendino (Catania) and Dr Maria Cristina Zingaretti (Ancona) for their excellent technical support and Prof Riccarda Granata (Torino) for the critical reading of the paper.

Funding

PRIN 2017 to Saverio Cinti; FIR Unict 2014 and Mediterranean Foundation “G.B. Morgagni” Catania to Sergio Castorina. The sources of funding had no involvement in the study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.

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Correspondence to Saverio Cinti.

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Castorina, S., Barresi, V., Luca, T. et al. Gastric ghrelin cells in obese patients are hyperactive. Int J Obes 45, 184–194 (2021). https://doi.org/10.1038/s41366-020-00711-3

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