Inhibition of ghrelin O-acyltransferase attenuates food deprivation-induced increases in ingestive behavior
Open accessAbstract
Ghrelin is an orexigenic hormone produced by the stomach in direct proportion to the time since the last meal and has therefore been called a 'hunger signal'. The octanoylation of ghrelin is critical for its orexigenic functions and is dependent upon ghrelin O-acyltransferase (GOAT) catalyzation. The GOAT inhibitor, GO-CoA-Tat, decreases the circulating concentrations of octanoylated ghrelin and attenuates weight gain on a high fat diet in mice. Unlike rats and mice, Siberian hamsters and humans do not increase food intake after food deprivation, but increase food hoarding after food deprivation. In Siberian hamsters, exogenous ghrelin increases ingestive behaviors similarly to 48-56 h food deprivation. Therefore, we tested the necessity of increased ghrelin in food-deprived Siberian hamsters to stimulate ingestive behaviors. To do so we used our simulated natural housing system that allows hamsters to forage for and hoard food. Animals were given an injection of GO-CoA-Tat (i.p., 11 μmol/kg) every 6h because that is the duration of its effective inhibition of octanoylated ghrelin concentrations during a 48 h food deprivation. We found that GO-CoA-Tat attenuated food foraging (0-1h), food intake (0-1 and 2-4h), and food hoarding (0-1h and 2 and 3 days) post-refeeding compared with saline treated animals. This suggests that increased octanoylated ghrelin concentrations play a role in the food deprivation-induced increases in ingestive behavior. Therefore, ghrelin is a critical aspect of the multi-faceted mechanisms that stimulate ingestive behaviors, and might be a critical point for a successful clinical intervention scheme in humans.
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In preclinical studies, treatment with GOAT inhibitor resulted in decreased food intake.
“In preclinical studies, treatment with GOAT inhibitor resulted in decreased food intake [77, 80].”
From Long-Term Efficacy and Safety of Anti-Obesity Treatment: Where Do We Stand? (2021) · cites this paper as [77]
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- Authors
- Teubner, B. J. W., Garretson, J. T., Hwang, Y., Cole, P. A., & Bartness, T. J.
- Affiliations
- Georgia State University (US)
- Johns Hopkins University (US)
- Corresponding author
- Bartness, Timothy J.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 63
- Issue
- 4
- Pages
- 667-673
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC3633643
- OpenAlex
- W2002739974
- Cited by
- 21
- References
- 55
- Citations by year
- 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2017: 3 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 3
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Agriculture
- Georgia State University
- National Institutes of Health (1f32dk091984-01a1)
- National Institute of General Medical Sciences (U54GM103520)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIH R01 DK078358, R01DK078358, NIH F32 DK091984, F32-DK-091984, R24DK093434)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- ghrelin, ghrelin O-acyltransferase, octanoylation, food deprivation, food hoarding, food foraging, dietary intake, Siberian hamster, hunger signals, refeeding, appetite regulation
- MeSH terms
- Acyltransferases, Animals, Body Weight, Eating, Enzyme Inhibitors, Feeding Behavior, Food Deprivation, Cricetinae, Male, Peptides, Phodopus, Ghrelin
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