This 2011 review from Kurume University (Kojima's group, who discovered ghrelin in 1999) synthesizes structural, regulatory, and functional evidence across species . Key reported findings: (1) the 28-aa mature peptide is encoded in exons 1β2; (2) des-acyl ghrelin cannot bind GHS-R nor release GH, yet induces food intake after intracerebroventricular injection, implying a non-GPCR mechanism the authors explicitly flag as unresolved; (3) acylation is essential for GH release and appetite stimulation; (4) the N-terminal 10 amino acids are identical across mammals, supporting their functional necessity. An earlier comprehensive review corroborated this multi-functional framingβGH release, appetite, metabolism, cardiovascular and reproductive rolesβalso acknowledging inconsistent acylated-vs-desacyl assay measurements and over-reliance on rodent models .
The review reports these identity values and notes functional divergence: chicken ghrelin suppresses feeding in neonatal chicks (unlike mammals), and bullfrog ghrelin's Thr3 carries octanoyl or decanoyl modifications .
What the review does well: authoritative provenance (JSPS/MEXT/Takeda funding disclosed; no commercial pharma sponsor listed ), honest acknowledgment of open questions (des-acyl ghrelin mechanism), and comprehensive species coverage.
Blind spots and limitations: (a) It is a narrative review with no systematic search strategy, so citation bias is possible. (b) Knowledge half-life: GOAT was "recently identified" at writing; subsequent work (e.g., GLP-1RβmTORC1 suppression of ghrelin synthesis ) postdates it, so regulatory-pathway coverage is now incomplete. (c) Rodent-to-human extrapolation pervades the field it summarizes. (d) Des-acyl ghrelin's receptor remains unidentified β the authors concede this, but the mechanism is still unresolved more than a decade later. (e) Clinical translation is thin; even later ghrelin-system reviews in oncology emphasize heterogeneous, inconclusive evidence .
Confidence note: The structural/evolutionary claims rest on strong primary purification and cloning data (high confidence). Claims about des-acyl ghrelin's central feeding effect are based on intracerebroventricular injections β pharmacologic, not physiological, evidence (moderate confidence). Disproving the review's framing would require identifying the des-acyl ghrelin receptor and showing GOAT-independent acylation pathways account for measurable acyl ghrelin in GOAT-deficient models.
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