The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
Amino acids inhibit Agrp gene expression via an mTOR-dependent mechanism
Open accessAbstract
Metabolic fuels act on hypothalamic neurons to regulate feeding behavior and energy homeostasis, but the signaling mechanisms mediating these effects are not fully clear. Rats placed on a low-protein diet (10% of calories) exhibited increased food intake (P < 0.05) and hypothalamic Agouti-related protein (Agrp) gene expression (P = 0.002). Direct intracerebroventricular injection of either an amino acid mixture (RPMI 1640) or leucine alone (1 mug) suppressed 24-h food intake (P < 0.05), indicating that increasing amino acid concentrations within the brain is sufficient to suppress food intake. To define a cellular mechanism for these direct effects, GT1-7 hypothalamic cells were exposed to low amino acids for 16 h. Decreasing amino acid availability increased Agrp mRNA levels in GT1-7 cells (P < 0.01), and this effect was attenuated by replacement of the amino acid leucine (P < 0.05). Acute exposure to elevated amino acid concentrations increased ribosomal protein S6 kinase phosphorylation via a rapamycin-sensitive mechanism, suggesting that amino acids directly stimulated mammalian target of rapamycin (mTOR) signaling. To test whether mTOR signaling contributes to amino acid inhibition of Agrp gene expression, GT1-7 cells cultured in either low or high amino acids for 16 h and were also treated with rapamcyin (50 nM). Rapamycin treatment increased Agrp mRNA levels in cells exposed to high amino acids (P = 0.01). Taken together, these observations indicate that amino acids can act within the brain to inhibit food intake and that a direct, mTOR-dependent inhibition of Agrp gene expression may contribute to this effect.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“a number of studies demonstrate that low-protein diets induce hyperphagia, particularly in rodent models”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [73]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Central nervous system control of food intake
Schwartz, M. W., Woods, S. C., Porte, D., Seeley, R. J., & Baskin, D. G. (2000) · Nature · doi:10.1038/35007534 · Cited by 6,451
Central nervous system control of food intake and body weight
Morton, G. J., Cummings, D. E., Baskin, D. G., Barsh, G. S., & Schwartz, M. W. (2006) · Nature · doi:10.1038/nature05026 · Cited by 2,503
AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus
Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.-B., Lee, A., Xue, B., Mu, J., Foufelle, F., Ferré, P., Birnbaum, M. J., et al. (2004) · Nature · doi:10.1038/nature02440 · Cited by 1,637
Hypothalamic mTOR Signaling Regulates Food Intake
Cota, D., Proulx, K., Smith, K. A. B., Kozma, S. C., Thomas, G., Woods, S. C., & Seeley, R. J. (2006) · Science · doi:10.1126/science.1124147 · Cited by 1,278
Fingar, D. C., & Blenis, J. (2004) · Oncogene · doi:10.1038/sj.onc.1207542 · Cited by 1,264
Flier, J. S. (2004) · Cell · doi:10.1016/s0092-8674(03)01081-x · Cited by 1,124
Mammalian TOR: a homeostatic ATP sensor
Dennis, P. B., Jaeschke, A., Saitoh, M., Fowler, B., Kozma, S. C., & Thomas, G. (2001) · Science · doi:10.1126/science.1063518 · Cited by 962
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654
Critical role for peptide YY in protein-mediated satiation and body-weight regulation
Batterham, R. L., Heffron, H., Kapoor, S., Chivers, J. E., Chandarana, K., Herzog, H., le Roux, C. W., Thomas, E. L., Bell, J. D., & Withers, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.08.001 · Cited by 653
Kimball, S. R., & Jefferson, L. S. (2006) · Journal of Nutrition · doi:10.1093/jn/136.1.227s · Cited by 637
Cited by
Sorted by citations
High-fat diet-induced obesity in animal models
Hariri, N., & Thibault, L. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000168 · Cited by 1,142
The Brain, Appetite, and Obesity
Berthoud, H., & Morrison, C. D. (2007) · Annual Review of Psychology · doi:10.1146/annurev.psych.59.103006.093551 · Cited by 699
Self-citationFGF21 is an endocrine signal of protein restriction
Laeger, T., Henagan, T. M., Albarado, D. C., Redman, L. M., Bray, G. A., Noland, R. C., Münzberg, H., Hutson, S. M., Gettys, T. W., Schwartz, M. W., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74915 · Cited by 593
Self-citationDietary protein, weight loss, and weight maintenance
Westerterp-Plantenga, M. S., Nieuwenhuizen, A., Tomé, D., Soenen, S., & Westerterp, K. R. (2009) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-080508-141056 · Cited by 570
Autophagy in Hypothalamic AgRP Neurons Regulates Food Intake and Energy Balance
Kaushik, S., Rodriguez-Navarro, J. A., Arias, E., Kiffin, R., Sahu, S., Schwartz, G. J., Cuervo, A. M., & Singh, R. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.008 · Cited by 382
Metadata
- Authors
- Morrison, C. D., Xi, X., White, C. L., Ye, J., & Martin, R. J.
- Affiliations
- Pennington Biomedical Research Center (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2007-07
- Volume
- 293
- Issue
- 1
- Pages
- E165-E171
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC2596875
- OpenAlex
- W2015145490
- Cited by
- 183
- References
- 36
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 15 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 13 · 2015: 7 · 2014: 7 · 2013: 11 · 2012: 16
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (P20GM103528, P30GM118430)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK072476)
- National Institute of Neurological Disorders and Stroke (NS-051570, R03NS051570)
- National Center for Research Resources (RR 021945, P20RR021945)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- amino acids, agouti-related protein, mTOR signaling, leucine, food intake regulation, hypothalamic neurons, GT1-7 cells, S6K, rapamycin, low-protein diet, energy homeostasis
- MeSH terms
- Amino Acids, Animals, Cells, Cultured, Eating, Gene Expression Regulation, Hypothalamus, Male, Protein Kinases, Signal Transduction, Rats, Sprague-Dawley, Diet, Protein-Restricted, Intercellular Signaling Peptides and Proteins, Rats, Agouti-Related Protein, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
