Protein intake, brain amino acid and serotonin concentrations and protein self-selection
Abstract
Analysis of evidence of associations among dietary protein content, brain amino acid and serotonin concentrations, and protein self-selection by rats suggests that 1) protein intake is not regulated precisely, although rats will select between low and high protein diets to obtain an adequate, but not excessive, amount of protein; 2) associations between brain serotonin concentration and protein intake are weak, although consumption of single meals of protein-deficient diets will elevate brain serotonin concentration; 3) the nature of signals that drive rats to avoid diets containing inadequate or excessive amounts of protein remains obscure; (4) whole brain amino acid and serotonin concentrations are quite stable over the usual range of protein intakes, owing to competition among amino acids for uptake across the blood-brain barrier and effective metabolic regulation of blood amino acid concentrations; 5) protein intake and preference are not in themselves regulated, but what appears to be regulation of intake and preference is a reflection of the responses of systems for control of plasma amino acid concentrations; and (6) the relative stability of the average protein intake of groups of self-selecting rats (which gives the appearance of regulation) results from averaging the variable behavioral responses--learned aversions and preferences--of rats to the variety of sensory cues arising from diets that differ in protein content.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
High-protein diets tend to suppress food intake in both humans and rodents.
“High-protein diets tend to suppress food intake in both humans and rodents”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [65]
Cites
Brain Serotonin Content: Physiological Regulation by Plasma Neutral Amino Acids
Fernstrom, J. D., & Wurtman, R. J. (1972) · Science · doi:10.1126/science.178.4059.414 · Cited by 1,166 · see citing works
Specific hungers and poison avoidance as adaptive specializations of learning.
Rozin, P. N., & Kalat, J. W. (1971) · Psychological Review · doi:10.1037/h0031878 · Cited by 1,165 · see citing works
Branched-Chain Amino Acid Metabolism
Harper, A. E., Miller, R. H., & Block, K. P. (1984) · Annual Review of Nutrition · doi:10.1146/annurev.nu.04.070184.002205 · Cited by 1,011 · see citing works
Self-citationBranched-Chain Amino Acid Metabolism
Yudkoff, M. (1999) · Cited by 763 · see citing works
Brain Serotonin Content: Increase Following Ingestion of Carbohydrate Diet
Fernstrom, J. D., & Wurtman, R. J. (1971) · Science · doi:10.1126/science.174.4013.1023 · Cited by 734 · see citing works
Silverstone, T. (1976) · Cited by 272 · see citing works
Cecil, R. L., & KENNEDY, F. (1927) · The American Journal of the Medical Sciences · doi:10.1097/00000441-194402000-00019 · Cited by 260 · see citing works
Food intake regulation in the weanling rat: self-selection of protein and energy
Musten, B., Peace, D., & Anderson, G. H. (1974) · The Journal of Nutrition · doi:10.1093/jn/104.5.563 · Cited by 189 · see citing works
Tryptophan Availability and Serotonin Synthesis
Leathwood, P. D. (1987) · Proceedings of The Nutrition Society · doi:10.1079/pns19870018 · Cited by 170 · see citing works
Peters, J. C., & Harper, A. E. (1985) · The Journal of Nutrition · doi:10.1093/jn/115.3.382 · Cited by 163 · see citing works
Control of protein and energy intake: Role of plasma amino acids and brain neurotransmitters
Anderson, G. H. (1979) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y79-158 · Cited by 156 · see citing works
Jeanningros, R. (1982) · Physiology & Behavior · doi:10.1016/0031-9384(82)90094-4 · Cited by 144 · see citing works
Associations among food and protein intake, serine dehydratase, and plasma amino acids
Anderson, H., Benevenga, N., & Harper, A. E. (1968) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1968.214.5.1008 · Cited by 142 · see citing works
Self-citationAshley, D. V. M., & Anderson, G. H. (1975) · Journal of Nutrition · doi:10.1093/jn/105.11.1412 · Cited by 126 · see citing works
Effect of protein dose on serum glucose and insulin response to sugars
Spiller, G. A., Jensen, C. D., Pattison, T. S., Chuck, C., Whittam, J. H., & Scala, J. (1987) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/46.3.474 · Cited by 120 · see citing works
Yokogoshi, H., & Wurtman, R. J. (1986) · Metabolism · doi:10.1016/0026-0495(86)90225-8 · Cited by 102 · see citing works
EFFECT OF VARIATIONS IN PROTEIN INTAKE ON ENZYMES OF AMINO ACID METABOLISM
Harper, A. E. (1965) · Canadian Journal of Biochemistry · doi:10.1139/o65-176 · Cited by 91 · see citing works
Self-citationNormal plasma free amino acid values in adults: The influence of some common physiological variables
Scriver, C. R., Gregory, D. M., Sovetts, D., & Tissenbaum, G. (1985) · Metabolism · doi:10.1016/0026-0495(85)90112-x · Cited by 88 · see citing works
Acquired protein appetite in rats: Dependence on a protein-specific need state
Gibson, E. L., & Booth, D. (1986) · Cellular and Molecular Life Sciences · doi:10.1007/bf01940706 · Cited by 78 · see citing works
Amino Acid Availability and Brain Function in Health and Disease
Huether, G. (1988) · Springer eBooks · doi:10.1007/978-3-642-73175-4 · Cited by 66 · see citing works
THE CHOICE BETWEEN ADEQUATE AND INADEQUATE DIETS, AS MADE BY RATS
Osborne, T. B., Mendel, L. B., Ferry, E. L., et al. (1918) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)86477-8 · Cited by 59 · see citing works
Ashley, D. V. M., & Anderson, G. H. (1975) · Journal of Nutrition · doi:10.1093/jn/105.11.1405 · Cited by 57 · see citing works
Factors affecting the selection of protein and carbohydrate from a dietary choice
Ashley, D. V. M. (1985) · Nutrition Research · doi:10.1016/s0271-5317(85)80164-0 · Cited by 54 · see citing works
Short-Term Zinc Deficiency in the Rat and Self-Selection of Dietary Protein Level
Reeves, P. G., & O’Dell, B. L. (1981) · Journal of Nutrition · doi:10.1093/jn/111.2.375 · Cited by 52 · see citing works
PETERS, J., & HARPER, A. (1984) · Physiology & Behavior · doi:10.1016/0031-9384(84)90048-9 · Cited by 52 · see citing works
Self-citationProtein and energy consumption, plasma amino acid ratios, and brain neurotransmitter concentrations
Peters, J. C., & Harper, A. E. (1981) · Physiology & Behavior · doi:10.1016/0031-9384(81)90271-7 · Cited by 52 · see citing works
Self-citationAcute effects of dietary protein on food intake, tissue amino acids, and brain serotonin
Peters, J. C., & Harper, A. E. (1987) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1987.252.5.r902 · Cited by 50 · see citing works
Self-citationFood intake and selection after peripheral tryptophan
Morris, P., Li, E. T. S., MacMillan, M. L., & Anderson, G. H. (1987) · Physiology & Behavior · doi:10.1016/0031-9384(87)90201-0 · Cited by 40 · see citing works
L-Tryptophan injection fails to alter nutrient selection by rats
Peters, J. C., Bellissimo, D. B., & Harper, A. E. (1984) · Physiology & Behavior · doi:10.1016/0031-9384(84)90138-0 · Cited by 39 · see citing works
Self-citationMitchell, H. S., & Mendel, L. B. (1921) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1921.58.2.211 · Cited by 33 · see citing works
Jeanningros, R., & Mei, N. (1980) · Brain Research · doi:10.1016/0006-8993(80)91065-3 · Cited by 32 · see citing works
Anderson, G. H., & Ashley, D. V. M. (1977) · Life Sciences · doi:10.1016/0024-3205(77)90002-9 · Cited by 25 · see citing works
(1984) · Elsevier eBooks · doi:10.1016/b978-0-127-15950-8.x5001-x · Cited by 25 · see citing works
Dietary preference and diseases of age
Ross, M. H., & Brás, G. (1974) · Nature · doi:10.1038/250263a0 · Cited by 24 · see citing works
“LA FIXITÉ DU MILIEU INTÉRIEUR EST LA CONDITION DE LA VIE LIBRE.” (C laude B ernard )1
Barcroft, J. (1932) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.1962.tb01036.x · Cited by 24 · see citing works
Amino Acid Signals and Food Intake and Preference: Relation to Body Protein Metabolism
Harper, A. E., & Peters, J. C. (1983) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-0348-6540-1_8 · Cited by 19 · see citing works
Self-citationRomsos, D. R., Chee, K. M., & Bergen, W. G. (1982) · Journal of Nutrition · doi:10.1093/jn/112.3.505 · Cited by 15 · see citing works
Suppression of afferent activity of the hepatic vagus nerve by anomers of D-glucose
Niijima, A., Fukuda, A., Taguchi, T., et al. (1983) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1983.244.5.r611 · Cited by 13 · see citing works
Nutritional & Metabolic Control of Brain Amino Acid Concentrations
Harper, A. E., & Tews, J. K. (1988) · Springer eBooks · doi:10.1007/978-3-642-73175-4_1 · Cited by 10 · see citing works
Self-citationNEUROTRANSMITTER PRECURSORS: FROM ANIMAL EXPERIMENTS TO HUMAN APPLICATIONS
Leathwood, P. D. (2009) · Nutrition Reviews · doi:10.1111/j.1753-4887.1986.tb07697.x · Cited by 8 · see citing works
A skeptical view of the role of central serotonin in the selection and intake of protein
Peters, J. C., & Harper, A. E. (1987) · Appetite · doi:10.1016/0195-6663(87)90018-3 · Cited by 7 · see citing works
Self-citationEffect of pre-feeding ammonium acetate on food intake of rats fed high protein diets
Semon, B. A., Leung, P. M. B., & Rogers, Q. R. (1988) · Physiology & Behavior · doi:10.1016/0031-9384(88)90179-5 · Cited by 3 · see citing works
VARIABILITY OF NUTRIENT REQUIREMENTS
Payne, P. (1984) · Elsevier eBooks · doi:10.1016/b978-0-12-715950-8.50016-0 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Metabolic Evidence for Adaptation to a High Protein Diet in Rats
Jean, C., Rome, S., Mathé, V., Huneau, J.-F., Aattouri, N., Fromentin, G., Achagiotis, C. L., & Tomé, D. (2001) · The Journal of Nutrition · doi:10.1093/jn/131.1.91 · Cited by 189 · see citing works
Amino acids inhibit <i>Agrp</i> gene expression via an mTOR-dependent mechanism
Morrison, C. D., Xi, X., White, C. L., Ye, J., & Martin, R. J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00675.2006 · Cited by 183 · see citing works
A Protein-Stat Mechanism for Regulation of Growth and Maintenance of the Lean Body Mass
Millward, D. J. (1995) · Nutrition Research Reviews · doi:10.1079/nrr19950008 · Cited by 119 · see citing works
Protein, amino acids and the control of food intake
Tome, D. (2004) · British Journal of Nutrition · doi:10.1079/bjn20041138 · Cited by 102 · see citing works
A high-protein diet enhances satiety without conditioned taste aversion in the rat
Bensaı̈d, A., Tomé, D., L'Heureux-Bourdon, D., Even, P., Gietzen, D., Morens, C., Gaudichon, C., Larue-Achagiotis, C., & Fromentin, G. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00977-0 · Cited by 100 · see citing works
Homeostatic regulation of protein intake: in search of a mechanism
Morrison, C. D., Reed, S. D., & Henagan, T. M. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00609.2011 · Cited by 99 · see citing works
FGF21 and the physiological regulation of macronutrient preference
Hill, C. M., Qualls-Creekmore, E., Berthoud, H.-R., Soto, P., Yu, S., McDougal, D. H., Münzberg, H., & Morrison, C. D. (2020) · Endocrinology · doi:10.1210/endocr/bqaa019 · Cited by 99 · see citing works
Protein selection, food intake, and body composition in response to the amount of dietary protein
White, B. D., Porter, M. H., & Martin, R. J. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(99)00232-2 · Cited by 91 · see citing works
Neural and metabolic regulation of macronutrient intake and selection
Berthoud, H.-R., Münzberg, H., Richards, B. K., & Morrison, C. D. (2012) · Proceedings of The Nutrition Society · doi:10.1017/s0029665112000559 · Cited by 87 · see citing works
Control of protein and energy intake - brain mechanisms
Davidenko, O., Darcel, N., Fromentin, G., & Tomé, D. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.73 · Cited by 63 · see citing works
The protein status of rats affects the rewarding value of meals due to their protein content
Chaumontet, C., Recio, I., Fromentin, G., Benoit, S., Piedcoq, J., Darcel, N., & Tomé, D. (2018) · The Journal of Nutrition · doi:10.1093/jn/nxy060 · Cited by 30 · see citing works
- Authors
- Harper, A. E., & Peters, J. C.
- Affiliations
- University of Wisconsin–Madison (US)
- ORCID
- Peters, John C.
- Venue
- The Journal of Nutrition
- Publisher
- Elsevier BV
- Published
- 1989-05
- Volume
- 119
- Issue
- 5
- Pages
- 677-689
- ISSN
- 0022-3166 (ISSN-L)
- OpenAlex
- W2130370422
- Cited by
- 103
- References
- 43
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2021: 1 · 2020: 3 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 6 · 2013: 5 · 2012: 5
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK10747)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Nursing › Nutrition and Dietetics › Nutrition, Health and Food Behavior
- Keywords
- protein intake, brain serotonin, brain amino acids, protein-deficient diet, learned aversion, learned preferences, rats, food intake regulation
- MeSH terms
- Amino Acids, Animals, Brain, Dietary Proteins, Food Preferences, Humans, Osmolar Concentration, Serotonin, Tryptophan
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
