Abstract
Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. This meta-analysis aimed to investigate the potential differences in plasma acyl ghrelin (AG) and des-acyl ghrelin (DAG) concentrations between normal weight and obese adults. Systematic literature searches of PubMed, Embase and Web of Science through October 2021 were conducted for articles reporting AG or DAG levels in obesity and normal weight, and 34 studies with 1863 participants who met the eligibility criteria were identified. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated to evaluate group differences in circulating AG and DAG levels. Pooled effect size showed significantly lower levels of baseline AG (SMD: − 0.85; 95% CI: − 1.13 to − 0.57; PSMD < 0.001) and DAG (SMD: − 1.06; 95% CI: − 1.43 to − 0.69; PSMD < 0.001) in obese groups compared with healthy controls, and similar results were observed when subgroup analyses were stratified by the assay technique or storage procedure. Postprandial AG levels in obese subjects were significantly lower than those in controls when stratified by different time points (SMD 30 min: − 0.85, 95% CI: − 1.18 to − 0.53, PSMD < 0.001; SMD 60 min: − 1.00, 95% CI: − 1.37 to − 0.63, PSMD < 0.001; SMD 120 min: − 1.21, 95% CI: − 1.59 to − 0.83, PSMD < 0.001). In healthy subjects, a postprandial decline in AG was observed at 120 min (SMD: − 0.42; 95% CI: − 0.77 to − 0.06; PSMD = 0.021) but not in obese subjects (SMD: − 0.28; 95% CI: − 0.60 to 0.03; PSMD = 0.074). The mean change in AG concentration was similar in both the obese and lean health groups at each time point (ΔSMD30min: 0.31, 95% CI: − 0.35 to 0.97, PSMD = 0.359; ΔSMD60min: 0.17, 95% CI: − 0.12 to 0.46, PSMD = 0.246; ΔSMD120min: 0.21, 95% CI: − 0.13 to 0.54, PSMD = 0.224). This meta-analysis strengthens the clinical evidence supporting the following: lower baseline levels of circulating AG and DAG in obese individuals; declines in postprandial circulating AG levels, both for the healthy and obese individuals; a shorter duration of AG suppression in obese subjects after meal intake. These conclusions have significance for follow-up studies to elucidate the role of various ghrelin forms in energy homeostasis.
Highlights
Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses
acyl ghrelin (AG) is a 28 amino acid peptide hormone often seen as the active form of ghrelin because of its unique posttranslational acylation at the serine 3 residue, which is catalyzed by ghrelinO-acyltransferase (GOAT) and is essential for binding a growth hormone secretagogue receptors (GHSRs) with high affinity[14,15]
Current knowledge regarding circulating ghrelin levels describes that circulating ghrelin levels elevated during shortterm fasting and decreased upon meal ingestion in healthy h umans[6,28,29], which is consistent with its unique mechanism of action on orexigenic hormone evolution for energy storage and seeking[30]
Summary
Ghrelin is the only known orexigenic gut hormone, and its synthesis, secretion and degradation are affected by different metabolic statuses. People with obesity usually exhibit lower fasting levels of ghrelin[31,32] with a decline in postprandial suppression[33], and different published studies that focus on obesity have reported a negative correlation between plasma ghrelin levels and body mass index[31,32] This abnormality may result from physiological adaptation with a positive energy balance in obese participants[31]; it is important to note that merely evaluating total ghrelin could not reflect the real metabolic status in obesity, since acyl and des-acyl ghrelin interact with different receptors and appear to have opposite actions. Recent observations have shown inconsistent results in the circulating levels of AG and DAG in individuals with obesity, reflected at baseline and at postprandial levels[36,37,38,39,40,41,42,43,44]
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