The Homeostatic Force of Ghrelin

Abstract

Ghrelin, a gastric-derived acylated peptide, regulates energy homeostasis by transmitting information about peripheral nutritional status to the brain, and is essential for protecting organisms against famine. Ghrelin operates brain circuits to regulate homeostatic and hedonic feeding. Recent research advances have shed new light on ghrelin's multifaceted roles in cellular homeostasis, which could maintain the internal environment and overcome metaflammation in metabolic organs. Here, we highlight our current understanding of the regulatory mechanisms of the ghrelin system in energy metabolism and cellular homeostasis and its clinical trials. Future studies of ghrelin will further elucidate how the stomach regulates systemic homeostasis.

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

“…In summary, in the present study, we found that central administration of the GHSR antagonist [D-Lys3]-GHRP-6 or JMV2959 did not affect HF intake escalation over the successive days or cumulative 4-day HF intake, supporting the notion that circulating ghrelin does not affect brain areas regulating binge-like HF intake. By contrast, i.c.v.-injected K-(D-1-Nal)-FwLL-NH 2 reduced daily HF intake, HF intake escalation over the successive days and cumulative 4-day HF intake, in a similar fashion to that seen for i.c.v.-injected LEAP2 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] . Notably, central administration of these GHSR synthetic ligands did not affect 22hour food intake and body weight.…”

“…43 Because we recently demonstrated that the N-terminal sequence of LEAP2 confers full receptor binding and activity, 7 a peptide containing the initial 14 residues of N-terminal LEAP2 sequence (hereafter named LEAP2 1-14 ) was employed as an analogue of full-length LEAP2. LEAP2 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] was assembled on solid support using Fmoc chemistry and starting from Amphisphere 40 RAM resin (Agilent Technologies Inc., Santa Clara, CA, USA), purified by reverse phase-high-performance liquid chromatography and characterised by liquid chromatography-mass spectrometry and matrix-assisted laser desorption/ionization-tandem mass spectrometry with a purity > 95%, as described previously. 7 LEAP2 1-14 was dissolved in PBS.…”

“…To test whether central administrations of ghrelin or LEAP2 [1][2][3][4][5][6][7][8][9][10][11][12][13][14] affect HF intake in mice exposed to the binge-like eating protocol, ad lib. fed mice were daily i.c.v.-injected with aCSF alone or containing each of these peptides and subsequently exposed to a HF pellet for 4 consecutive days ( Figure 3A and (iii) a reduced cumulative 4-day HF intake.…”

“…The growth hormone secretagogue receptor (GHSR) is a G protein‐coupled receptor (GPCR) that is highly expressed in the brain . GHSR signalling controls a variety of functions, including food intake, growth hormone secretion and glucose homeostasis, amongst others . Endogenous ligands of GHSR include ghrelin, which is an acylated peptide mainly produced in the gastrointestinal tract that activates GHSR, and the recently described liver‐expressed antimicrobial peptide 2 (LEAP2), which is mainly expressed in the liver and small intestine that antagonises ghrelin‐evoked GHSR activation .…”

Plasma desacyl ghrelin‑to‑acyl ghrelin ratio is a predictor of postoperative complications and prognosis after pancreaticoduodenectomy

“…Univariate and multivariate analyses of prognostic factors (n=69). injury and promotes muscle regeneration and inhibit apoptosis in myoblasts cocultured with colon carcinoma cells (37,38). Specific receptors of DG that promote these activities have not been identified, and a feedback mechanism such as that with AG is unknown.…”