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Cited by 32Regulation of Appetite and ObesityPharmacology and Obesity TreatmentAdipokines, Inflammation, and Metabolic Diseases

Anti-ghrelin antibodies in appetite suppression: Recent advances in obesity pharmacotherapy

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Rotkvic, Vanja, Altabas, Velimir·2015·ImmunoTargets and Therapy
DOI 10.2147/itt.s60398PMC PMC4918252
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Abstract

Obesity is a medical condition caused by accumulated excess body fat with negative impact on patients' health, including decreased life expectancy. It has become a major health problem in most developed and developing countries, since the worldwide prevalence of obesity nearly doubled during the last 30 years. Consequently, novel treatments focusing on obesity are being investigated. Potential targets include several pathophysiological mechanisms involved in appetite control affecting multiple organ systems, like adipose tissue; some cell types in the stomach and gut; pancreas; thyroid gland; several hypothalamic areas; and centers located in the brainstem. One of the most important orexigenic neuropeptides is ghrelin, which is produced and secreted primarily by ghrelin cells located in the stomach and duodenum. In humans, plasma ghrelin levels rise when the stomach is empty and fall shortly after meal ingestion. In fat tissue, ghrelin increases fat storage. In the brain, it exerts its orexigenic action through activation of NPY/AgRP neurons in the arcuate nucleus. From the pharmacological point of view, it seems that opposing ghrelin activity could be used as a therapeutic principle in treating obesity. The principal idea of antiobesity drugs is to augment anorexigenic and lipolytic signaling, or to block orexigenic and lipogenic mediators. Recent studies have shown that therapeutic vaccines could be a new approach in the development of antiobesity medications. A vaccine should provoke an immune response to a specific causal factor for a particular disease. Several types of anti-ghrelin vaccines have been developed so far, with significant immune response in terms of rising anti-ghrelin antibodies. However, in the only clinical trial performed yet, the results were disappointing, showing no additional weight loss in the study group. Until now, several studies have demonstrated the "proof of concept", but more studies are required to develop prophylactic and therapeutic vaccines to prevent and/or cure obesity.

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  • Studies targeting ghrelin receptor inhibition have not reported sufficient efficacy to encourage further clinical development.

    “While inhibition of the appetite-stimulating (orexigenic) hormone ghrelin may seem an attractive therapeutic target, studies targeting ghrelin receptor inhibition have not reported sufficient efficacy to encourage further clinical development [124].”

    From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [124]

    In “Vaccination as a form of obesity prophylaxis and/or treatment” (page unavailable), the paper reports that ghrelin receptor antagonists suppressed appetite and produced weight loss in rodents, calling ghrelin blocking a potential treatment target. Its disappointing human trial concerned an anti-ghrelin vaccine, not receptor inhibition; the paper does not conclude that receptor-antagonist studies lacked sufficient efficacy for further clinical development. (LLM, conf=0.82)

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Cited by

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Authors
Rotkvic, V., & Altabas, V.
Affiliations
University Hospital Centre Zagreb (HR)
Corresponding author
Altabas, Velimir
ORCID
Altabas, Velimir
Venue
ImmunoTargets and Therapy
Publisher
Informa UK Limited
Published
2015-07
Volume
4
Pages
123
ISSN
2253-1556 (ISSN-L)
DOI
10.2147/itt.s60398
PMC
PMC4918252
OpenAlex
W1802293277
Cited by
32
References
6
Citations by year
2025: 3 · 2024: 7 · 2023: 3 · 2022: 4 · 2021: 6 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 1 · 2014: 2
FWCI
0.11
Type
journal article
Language
en
Open access
Licence
Locations
  • ImmunoTargets and Therapy (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
ghrelin, obesity pharmacotherapy, appetite suppression, orexigenic peptides, NPY/AgRP neurons, arcuate nucleus, therapeutic vaccines, weight loss

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