The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.
Diet-Induced Obesity Causes Ghrelin Resistance in Arcuate NPY/AgRP Neurons
Abstract
Circulating ghrelin is decreased in obesity, and peripheral ghrelin does not induce food intake in obese mice. We investigated whether ghrelin resistance was a centrally mediated phenomenon involving dysregulated neuropeptide Y (NPY) and agouti-related peptide (AgRP) circuits. We show that diet-induced obesity (DIO) (12 wk) suppresses the neuroendocrine ghrelin system by decreasing acylated and total plasma ghrelin, decreasing ghrelin and Goat mRNA in the stomach, and decreasing expression of hypothalamic GHSR. Peripheral (ip) or central (intracerebroventricular) ghrelin injection was able to induce food intake and arcuate nucleus Fos immunoreactivity in chow-fed but not high-fat diet-fed mice. DIO decreased expression of Npy and Agrp mRNA, and central ghrelin was unable to promote expression of these genes. Ghrelin did not induce AgRP or NPY secretion in hypothalamic explants from DIO mice. Injection of NPY intracerebroventricularly increased food intake in both chow-fed and high-fat diet-fed mice, indicating that downstream NPY/AgRP neural targets are intact and that defective NPY/AgRP function is a primary cause of ghrelin resistance. Ghrelin resistance in DIO is not confined to the NPY/AgRP neurons, because ghrelin did not stimulate growth hormone secretion in DIO mice. Collectively, our data suggests that DIO causes ghrelin resistance by reducing NPY/AgRP responsiveness to plasma ghrelin and suppressing the neuroendocrine ghrelin axis to limit further food intake. Ghrelin has a number of functions in the brain aside from appetite control, including cognitive function, mood regulation, and protecting against neurodegenerative diseases. Thus, central ghrelin resistance may potentiate obesity-related cognitive decline, and restoring ghrelin sensitivity may provide therapeutic outcomes for maintaining healthy aging.
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“Indeed, ghrelin has lower orexigenic activity in DIO rodents due to a reduction in activation and plasticity of NPY/AgRP neurons 138.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [138]
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., & Kangawa, K. (1999) · Nature · doi:10.1038/45230 · Cited by 8,479
Ghrelin induces adiposity in rodents
Tschöp, M., Smiley, D. L., & Heiman, M. L. (2000) · Nature · doi:10.1038/35038090 · Cited by 3,949
A role for ghrelin in the central regulation of feeding
Nakazato, M., Murakami, N., Date, Y., Kojima, M., Matsuo, H., Kangawa, K., & Matsukura, S. (2001) · Nature · doi:10.1038/35051587 · Cited by 3,443
A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans
Cummings, D. E., Purnell, J. Q., Frayo, R. S., Schmidova, K., Wisse, B. E., & Weigle, D. S. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1714 · Cited by 2,940
A Receptor in Pituitary and Hypothalamus That Functions in Growth Hormone Release
Howard, A., Feighner, S., Cully, D., Arena, J. P., Liberator, P., Rosenblum, C., Hamelin, M., Hreniuk, D. L., Palyha, O., Anderson, J., et al. (1996) · Science · doi:10.1126/science.273.5277.974 · Cited by 2,106
Circulating Ghrelin Levels Are Decreased in Human Obesity
Tschöp, M. H., Weyer, C., Tataranni, P. A., Devanarayan, V., Ravussin, É., & Heiman, M. L. (2001) · Diabetes · doi:10.2337/diabetes.50.4.707 · Cited by 2,031
Cowley, M. A., Smith, R. G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K. L., Strasburger, C. J., Bidlingmaier, M., Esterman, M., Heiman, M. L., et al. (2003) · Neuron · doi:10.1016/s0896-6273(03)00063-1 · Cited by 1,679
Self-citationHigh-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
Kohsaka, A., Laposky, A. D., Ramsey, K. M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F. W., & Bass, J. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.006 · Cited by 1,528
Trophic Action of Leptin on Hypothalamic Neurons That Regulate Feeding
Bouret, S. G., Draper, S. J., & Simerly, R. B. (2004) · Science · doi:10.1126/science.1095004 · Cited by 1,247
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Sümer, E., Goren, H., Barın, B., Kosif, Y., Başer, Ö., Keleştemur, M. M., Yavuz, Y., Gül, Z., & Yılmaz, B. (2026) · Uludağ Üniversitesi Tıp Fakültesi Dergisi · doi:10.32708/uutfd.1896815
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Wasse, L. K. (2011) · Loughborough University Institutional Repository (Loughborough University)
Metadata
- Authors
- Briggs, D. I., Enriori, P. J., Lemus, M. B., Cowley, M. A., & Andrews, Z. B.
- Affiliations
- Monash University (AU)
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2010-09-08
- Volume
- 151
- Issue
- 10
- Pages
- 4745-4755
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2143711558
- Cited by
- 320
- References
- 57
- Citations by year
- 2026: 18 · 2025: 15 · 2024: 15 · 2023: 18 · 2022: 15 · 2021: 20 · 2020: 22 · 2019: 19 · 2018: 13 · 2017: 22 · 2016: 18 · 2015: 30 · 2014: 25 · 2013: 20 · 2012: 27
- FWCI
- 10.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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 resistance, diet-induced obesity, neuropeptide Y, agouti-related protein, arcuate nucleus, hypothalamic neurons, growth hormone secretagogue receptor, food intake regulation, growth hormone secretion, high-fat diet, ghrelin signaling
- MeSH terms
- Animals, Arcuate Nucleus of Hypothalamus, Cognition, Diet, Atherogenic, Drug Resistance, Eating, Goats, Male, Mice, Inbred C57BL, Mice, Obese, Neurons, Neuropeptide Y, Obesity, Growth Hormone, Mice, Agouti-Related Protein, Ghrelin
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