PMID-22385874 – Ghrelin Physiological Significance and Clinical Applications
Stengel A, Tache Y. "The physiological significance and potential clinical applications of ghrelin," Curr Pharm Des, 2012;18(31):4818-4833.
Quick Reference
| Property | Value |
|---|---|
| PMID | 22385874 |
| DOI | 10.2174/138161212803216951 |
| Year | 2012 |
| Journal | Current Pharmaceutical Design |
| Study Type | Narrative Review |
| Evidence Level | V |
| Sample | N/A (review) |
| Peptide(s) Studied | Ghrelin |
Key Findings
- Ghrelin is the only known circulating orexigenic (appetite-stimulating) hormone — plasma levels rise before meals and fall after eating
- Beyond GH secretion and appetite, ghrelin modulates: gastric acid secretion and motility, cardiovascular function, glucose metabolism, bone metabolism, immune function, and stress/anxiety
- Acyl-ghrelin (octanoylated) and des-acyl ghrelin have distinct biological activities; des-acyl ghrelin may antagonize some acyl-ghrelin effects
- Ghrelin O-acyltransferase (GOAT) is the enzyme responsible for the essential octanoyl modification at Ser3
- Clinical applications explored: cachexia/anorexia (cancer, COPD, heart failure), gastroparesis, functional dyspepsia, GH deficiency diagnosis
- Ghrelin levels are chronically elevated in anorexia nervosa and reduced in obesity (suggesting compensatory regulation)
- GHS-R1a exhibits significant constitutive activity (~50% of maximal signaling) even without ghrelin binding
Study Design
Comprehensive narrative review synthesizing data from molecular biology, animal studies, and clinical trials regarding ghrelin's physiological roles and therapeutic potential. Covers the full spectrum of ghrelin biology from receptor pharmacology to clinical applications.
Limitations
- Review article; no new primary data
- Published 2012; significant new data since on ghrelin-GOAT axis and ghrelin analogs
- Some clinical applications remain investigational with limited trial data
Clinical Relevance
This review provides the comprehensive physiological context needed to understand why targeting the ghrelin/GHS-R1a axis is therapeutically valuable. It explains why MK-677 (oral ghrelin mimetic), GHRP-6, GHRP-2, ipamorelin, and hexarelin all work through the same receptor system. The constitutive activity of GHS-R1a is particularly important — it means that inverse agonists (not just antagonists) could be developed for weight loss applications. For the vault, this note bridges endogenous ghrelin physiology to the entire GH secretagogue peptide class.
Related
#research #narrative-review #evidence-level-V #gh-axis #ghrelin #metabolic