The homeostatic role of neuropeptide Y in immune function and its impact on mood and behaviour
Open accessAbstract
Neuropeptide Y (NPY), one of the most abundant peptides in the nervous system, exerts its effects via five receptor types, termed Y1, Y2, Y4, Y5 and Y6. NPY's pleiotropic functions comprise the regulation of brain activity, mood, stress coping, ingestion, digestion, metabolism, vascular and immune function. Nerve-derived NPY directly affects immune cells while NPY also acts as a paracrine and autocrine immune mediator, because immune cells themselves are capable of producing and releasing NPY. NPY is able to induce immune activation or suppression, depending on a myriad of factors such as the Y receptors activated and cell types involved. There is an intricate relationship between psychological stress, mood disorders and the immune system. While stress represents a risk factor for the development of mood disorders, it exhibits diverse actions on the immune system as well. Conversely, inflammation is regarded as an internal stressor and is increasingly recognized to contribute to the pathogenesis of mood and metabolic disorders. Intriguingly, the cerebral NPY system has been found to protect against distinct disturbances in response to immune challenge, attenuating the sickness response and preventing the development of depression. Thus, NPY plays an important homeostatic role in balancing disturbances of physiological systems caused by peripheral immune challenge. This implication is particularly evident in the brain in which NPY counteracts the negative impact of immune challenge on mood, emotional processing and stress resilience. NPY thus acts as a unique signalling molecule in the interaction of the immune system with the brain in health and disease.
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There is abundant evidence that the central NPY system affects stress-related disorders such as anxiety and depression.
“There is abundant evidence that the central NPY system affects stress-related disorders such as anxiety and depression (for a review, see [181,182]).”
From Anxiety, depression, and the microbiome: A role for gut peptides (2018) · cites this paper as [181]
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NPY modulates PYY function in the regulation of energy balance and glucose homeostasis
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Baker, D. G., Bertram, T. M., Patel, P. M., Barkauskas, D. A., Clopton, P., Patel, S., Geracioti, T. D., Haji, U., O’Connor, D. T., Nievergelt, C. M., et al. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.04.020 · Cited by 32 · see citing works
NPY, NPY receptors, and DPP IV activity are modulated by LPS, TNF-α and IFN-γ in HUVEC
Silva, A. P., Cavadas, C., Baı̈sse-Agushi, B., et al. (2003) · Regulatory Peptides · doi:10.1016/s0167-0115(03)00191-5 · Cited by 32 · see citing works
Radler, M. E., Wright, B. J., Walker, F. R., Hale, M. W., & Kent, S. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.11.014 · Cited by 31 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Painsipp E Kofer MJ Farzi A Dischinger US Sinner F Herzog H Holzer P Neuropeptide Y and peptide YY protect from weight loss caused by Bacille Calmette-Guerin in mice Br J Pharmacol 2013 170 1014 1026 23992467 PMC3949650
- Smith PM Howitt MR Panikov N Michaud M Gallini CA Bohlooly-Y M Glickman JN Garrett WS The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis Science 2013 341 569 573 23828891 PMC3807819
Cited by
Sorted by citations
Fröhlich, E. E., Farzi, A., Mayerhofer, R., Reichmann, F., Jačan, A., Wagner, B., Zinser, E., Bordag, N., Magnes, C., Fröhlich, E., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.02.020 · Cited by 720 · see citing works
Self-citationAnxiety, depression, and the microbiome: A role for gut peptides
Lach, G., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0585-0 · Cited by 573 · see citing works
Neuropeptide Y: a stressful review
Reichmann, F., & Holzer, P. (2016) · Neuropeptides · doi:10.1016/j.npep.2015.09.008 · Cited by 490 · see citing works
Self-citationGut microbiota and the neuroendocrine system
Farzi, A., Fröhlich, E. E., & Holzer, P. (2018) · Neurotherapeutics · doi:10.1007/s13311-017-0600-5 · Cited by 478 · see citing works
Self-citationThe Role of the Microbiome-Brain-Gut Axis in the Pathogenesis of Depressive Disorder
Młynarska, E., Gadzinowska, J., Tokarek, J., Forycka, J., Szuman, A., Franczyk, B., & Rysz, J. (2022) · Nutrients · doi:10.3390/nu14091921 · Cited by 109 · see citing works
Visceral Inflammation and Immune Activation Stress the Brain
Holzer, P., Farzi, A., Hassan, A. M., Zenz, G., Jačan, A., & Reichmann, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01613 · Cited by 84 · see citing works
Self-citationLu, N., Li, M., Lei, H., Jiang, X., Tu, W., Lu, Y., & Xia, D. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.06.004 · Cited by 75 · see citing works
Zhang, T., & Kong, J. (2025) · Frontiers in Physiology · doi:10.3389/fphys.2025.1567603 · Cited by 19 · see citing works
- Authors
- Farzi, A., Reichmann, F., & Holzer, P.
- Affiliations
- Medical University of Graz (AT)
- Corresponding author
- Farzi, A.
- Venue
- Acta Physiologica
- Publisher
- Wiley
- Published
- 2015-01-09
- Volume
- 213
- Issue
- 3
- Pages
- 603-627
- ISSN
- 1748-1708 (ISSN-L)
- 1748-1716
- PMC
- PMC4353849
- OpenAlex
- W2105584322
- Cited by
- 145
- References
- 236
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 13 · 2023: 2 · 2022: 13 · 2021: 10 · 2020: 19 · 2019: 19 · 2018: 9 · 2017: 11 · 2016: 17 · 2015: 6
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Physiologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Austrian Science Fund (P23097-B18, P25912-B23)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- neuropeptide Y, immune function, mood disorders, depression, psychological stress, sickness behavior, neuroimmune interactions, NPY receptors, inflammation, stress resilience, immune homeostasis
- MeSH terms
- Affect, Animals, Behavior, Brain, Emotions, Homeostasis, Humans, Immune System, Inflammation, Neuropeptide Y, Obesity, Stress, Psychological, Signal Transduction, Receptors, Neuropeptide Y, Gastrointestinal Tract
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 ›
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