Novel Ghrelin Assays Provide Evidence for Independent Regulation of Ghrelin Acylation and Secretion in Healthy Young Men
Open accessAbstract
CONTEXT: Ghrelin, an acylated peptide hormone secreted from the gut, regulates appetite and metabolism. Elucidating its pattern of secretion in the fed and fasted states is important in the face of the obesity epidemic. OBJECTIVE: Our objective was to examine changes in circulating ghrelin and des-acyl ghrelin in response to meals and fasting using newly developed two-site sandwich assays and sample preservation protocols to allow specific detection of full-length forms. DESIGN: Ten-minute sampling was done for 26.5 h during a fed admission with standardized meals and on a separate admission during the final 24 h of a 61.5-h fast and continuing for 2.5 h after terminating the fast. SETTING: The study was conducted at the University Hospital General Clinical Research Center. PARTICIPANTS: Eight male volunteers participated, mean +/- sd age 24.5 +/- 3.7 yr and body mass index 24 +/- 2.1 kg/m(2). MAIN OUTCOME MEASURES: Ten-minute sampling profiles were assessed for ghrelin and des-acyl ghrelin, fed and fasting. RESULTS: In the fed state, ghrelin and des-acyl ghrelin showed similar dynamics; both were sharply inhibited by meals and increased at night. During fasting, ghrelin decreased to nadir levels seen postprandially, and des-acyl ghrelin remained near peak levels seen preprandially. Total full-length ghrelin (acyl plus des-acyl) levels remained unchanged. CONCLUSIONS: Meals inhibited secretion of both ghrelin and des-acyl ghrelin, yet long-term fasting inhibited acylation but not total secretion. Acylation may be regulated independently of secretion by nutrient availability in the gut or by esterases that cleave the acyl group. These studies highlight the importance of stringent conditions for sample collection and evaluation of full-length ghrelin and des-acyl ghrelin using specific two-site assays.
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All but one of the studies characterizing overnight acylated ghrelin profiles confirmed increased nocturnal total ghrelin and demonstrated a concomitant increase in acylated ghrelin.
“All [95, 166] but one [3] of the studies that have attempted to characterize the overnight profiles of acylated ghrelin in relation to unacylated ghrelin confirmed the increased nocturnal elevation in total ghrelin and demonstrated a concomitant increase in acylated ghrelin.”
From Sleep and metabolic function (2012) · cites this paper as [95]
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“4 h, respectively, have been reported for AG in human plasma and∼27min in rat serum, whereas the degradation t1/2 of total circulatory ghrelin has been estimated to be as short as ∼9-11min (De Vriese et al., 2004; Liu et al., 2008; Tong et al., 2013).”
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- Authors
- Liu, J., Prudom, C. E., Nass, R., Pezzoli, S. S., Oliveri, M. C., Johnson, M. L., Veldhuis, P., Gordon, D. A., Howard, A. D., Witcher, D. R., Geysen, H. M., Gaylinn, B. D., & Thorner, M. O.
- Affiliations
- University of Virginia (US)
- Bristol-Myers Squibb (United States) (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Thorner, Michael O.
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2008-05-01
- Volume
- 93
- Issue
- 5
- Pages
- 1980-1987
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC2386282
- OpenAlex
- W2066247992
- Cited by
- 248
- References
- 43
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2023: 11 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 11 · 2018: 11 · 2017: 17 · 2016: 14 · 2015: 8 · 2014: 15 · 2013: 20 · 2012: 23
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- University of Virginia
- Deutsches Krebsforschungszentrum
- Novo Nordisk
- National Institutes of Health (5r01dk076037-05)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK032632, R25DK064122, R01 DK-076037, R01 DK32632)
- National Center for Research Resources (K23RR018770, M01RR000847, M01-RR 00847, R01RR019991)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- ghrelin, des-acyl ghrelin, ghrelin acylation, ghrelin secretion, fasting, meals, appetite regulation, sample preservation
- MeSH terms
- Acylation, Adult, Butyrylcholinesterase, Enzyme-Linked Immunosorbent Assay, Fasting, Humans, Immune Sera, Male, Sensitivity and Specificity, Ghrelin
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