The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN
Open accessAbstract
Neuropepetide Y (NPY) is best known for its powerful stimulation of food intake and its effects on reducing energy expenditure. However, the pathways involved and the regulatory mechanisms behind this are not well understood. Here we demonstrate that NPY derived from the arcuate nucleus (Arc) is critical for the control of sympathetic outflow and brown adipose tissue (BAT) function. Mechanistically, a key change induced by Arc NPY signaling is a marked Y1 receptor-mediated reduction in tyrosine hydroxylase (TH) expression in the hypothalamic paraventricular nucleus (PVN), which is also associated with a reduction in TH expression in the locus coeruleus (LC) and other regions in the brainstem. Consistent with this, Arc NPY signaling decreased sympathetically innervated BAT thermogenesis, involving the downregulation of uncoupling protein 1 (UCP1) expression in BAT. Taken together, these data reveal a powerful Arc-NPY-regulated neuronal circuit that controls BAT thermogenesis and sympathetic output via TH neurons.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Obesity is also accompanied by an increased NPY expression in the ARC.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [129]
In the citing paper
“This increase triggers a reduction in the expression of tyrosine hydroxylase neurons in the paraventricular nucleus (PVN) of the hypothalamus and consequently, diminishes the thermogenic activation of BAT and overall energy expenditure 129.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [129]
Citations
Cites
A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
Functional Brown Adipose Tissue in Healthy Adults
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N.-J., Enerbäck, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0808949 · Cited by 3,058
Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus
Cowley, M. A., Smart, J. L., Rubinstein, M., Cerdán, M. G., Diano, S., Horvath, T. L., Cone, R. D., & Low, M. J. (2001) · Nature · doi:10.1038/35078085 · Cited by 2,356
Gut hormone PYY3-36 physiologically inhibits food intake
Batterham, R. L., Cowley, M. A., Small, C. J., Herzog, H., Cohen, M. A., Dakin, C. L., Wren, A. M., Brynes, A. E., Low, M. J., Ghatei, M. A., et al. (2002) · Nature · doi:10.1038/nature00887 · Cited by 2,351
Self-citationAdipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 2×
“Obesity occurs when there is a significant imbalance between energy intake and energy expenditure (Rosen and Spiegelman, 2006).”
BackgroundHypothalamic integration: organization of the paraventricular and supraoptic nuclei
Swanson, L. W., & Sawchenko, P. E. (1983) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.06.030183.001413 · Cited by 1,991
Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein
Ollmann, M. M., Wilson, B. D., Yang, Y.-K., Kerns, J. A., Chen, Y., Gantz, I., & Barsh, G. S. (1997) · Science · doi:10.1126/science.278.5335.135 · Cited by 1,881
Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons
Hahn, T. M., Breininger, J. F., Baskin, D. G., & Schwartz, M. W. (1998) · Nature Neuroscience · doi:10.1038/1082 · Cited by 1,164
Paraventricular Nucleus:A Site for the Integration of Neuroendocrine and Autonomic Mechanisms
Swanson, L. W., & Sawchenko, P. E. (2008) · Neuroendocrinology · doi:10.1159/000123111 · Cited by 1,001
King, B. M. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.10.007 · Cited by 491
Zarjevski, N., Cusin, I., Vettor, R., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1993) · Endocrinology · doi:10.1210/endo.133.4.8404618 · Cited by 476
Localization of insulin receptor mRNA in rat brain by in situ hybridization
MARKS, J. L., PORTE, D., STAHL, W. L., & BASKIN, D. G. (1990) · Endocrinology · doi:10.1210/endo-127-6-3234 · Cited by 448
Kamegai, J., Tamura, H., Shimizu, T., Ishii, S., Sugihara, H., & Wakabayashi, I. (2000) · Endocrinology · doi:10.1210/endo.141.12.7920 · Cited by 379
Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Elmquist, J. K., Ahima, R. S., Elias, C. F., Flier, J. S., & Saper, C. B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.2.741 · Cited by 376
NPY and Y receptors: lessons from transgenic and knockout models
Lin, S., Boey, D., & Herzog, H. (2004) · Neuropeptides · doi:10.1016/j.npep.2004.05.005 · Cited by 289
Self-citationParaventricular hypothalamic nucleus: Axonal projections to the brainstem
Geerling, J. C., Shin, J., Chimenti, P. C., & Loewy, A. D. (2010) · Journal of Comparative Neurology · doi:10.1002/cne.22283 · Cited by 273
Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats
Egawa, M., Yoshimatsu, H., & Bray, G. A. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.260.2.r328 · Cited by 272
Ellacott, K. L. J. (2004) · Recent Progress in Hormone Research · doi:10.1210/rp.59.1.395 · Cited by 260
Sainsbury, A., Schwarzer, C., Couzens, M., Fetissov, S. O., Fürtinger, S., Jenkins, A. B., Cox, H. M., Sperk, G., Hökfelt, T. G. M., & Herzog, H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132043299 · Cited by 244
Self-citationChao, P.-T., Yang, L., Aja, S. M., Moran, T. H., & Bi, S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.02.019 · Cited by 213
Leptin receptor, NPY, POMC mRNA expression in the diet-induced obese mouse brain
Lin, S., Storlien, L. H., & Huang, X. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02580-4 · Cited by 198
Self-citationClinical significance of adaptive thermogenesis
Major, G., Doucet, É., Trayhurn, P., Astrup, A. V., & Tremblay, A. (2007) · International Journal of Obesity · doi:10.1038/sj.ijo.0803523 · Cited by 175
Hypothalamic projections to locus coeruleus neurons in rat brain
Reyes, B. A. S., Valentino, R. J., Xu, G., & Bockstaele, E. J. V. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04197.x · Cited by 172
The MONA LISA hypothesis in the time of leptin.
Bray, G. A., & York, D. A. (1998) · PubMed · Cited by 166
Role of Dorsomedial Hypothalamic Neuropeptide Y in Modulating Food Intake and Energy Balance
Yang, L., Scott, K. A., Hyun, J., Tamashiro, K. L., Tray, N., Moran, T. H., & Bi, S. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4379-08.2009 · Cited by 164
Neuropeptide Y is neuroproliferative for post‐natal hippocampal precursor cells
Howell, O. W., Scharfman, H. E., Herzog, H., Sundström, L., Beck‐Sickinger, A. G., & Gray, W. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01895.x · Cited by 158
Self-citationRole of ventromedial hypothalamus on sympathetic efferents of brown adipose tissue
Niijima, A., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.247.4.r650 · Cited by 148
Using brown adipose tissue to treat obesity – the central issue
Whittle, A. J., López, M., & Vidal‐Puig, A. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.04.001 · Cited by 138
Behavioural profile of a new mouse model for NPY deficiency
Karl, T., Duffy, L., & Herzog, H. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06306.x · Cited by 127
Self-citationRole of melanocortins in the central control of feeding
Vergoni, A. V., & Bertolini, A. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00538-0 · Cited by 125
Sainsbury, A., Rohner-Jeanrenaud, F., Cusin, I., Zakrzewska, K. E., Halban, P. A., Gaillard, R. C., & Jeanrenaud, B. (1997) · Diabetologia · doi:10.1007/s001250050820 · Cited by 116
Self-citationRole of the arcuate nucleus of the hypothalamus in regulation of body weight during energy deficit
Sainsbury, A., & Zhang, L. (2009) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2009.09.025 · Cited by 113
Self-citationFunctions for pro-opiomelanocortin-derived peptides in obesity and diabetes
Mountjoy, K. G. (2010) · Biochemical Journal · doi:10.1042/bj20091957 · Cited by 110
Nguyen, A., Mitchell, N. F., Lin, S., Macia, L., Yulyaningsih, E., Baldock, P. A. J., Enriquez, R. F., Zhang, L., Shi, Y., Zolotukhin, S., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0040191 · Cited by 104
Self-citationSainsbury, A., Cusin, I., Rohner‐Jeanrenaud, F., & Jeanrenaud, B. (1997) · Diabetes · doi:10.2337/diab.46.2.209 · Cited by 103
Self-citationTolle, V., & Low, M. J. (2007) · Diabetes · doi:10.2337/db07-0733 · Cited by 100
Peripheral neuropeptide Y Y1 receptors regulate lipid oxidation and fat accretion
Zhang, L., Macia, L., Turner, N. A., Enriquez, R. F., Riepler, S. J., Nguyen, A., Lin, S., Lee, N. J., Shi, Y. C., Yulyaningsih, E., et al. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.232 · Cited by 69
Self-citationBrown fat and obesity: the next big thing?
Stephens, M., Ludgate, M., & Rees, A. (2011) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2011.04018.x · Cited by 65
Peripheral‐Specific Y2 Receptor Knockdown Protects Mice From High‐Fat Diet‐Induced Obesity
Shi, Y., Lin, S., Castillo, L. E., Aljanova, A., Enriquez, R. F., Nguyen, A., Baldock, P. A. J., Zhang, L., Bijker, M. S., Macia, L., et al. (2011) · Obesity · doi:10.1038/oby.2011.99 · Cited by 61
Self-citationZHENG, J.-Q., Seki, M., Hayakawa, T., Ito, H., & Zyo, K. (1995) · Okajimas Folia Anatomica Japonica · doi:10.2535/ofaj1936.72.2-3_119 · Cited by 60
Horváth, T. L., Naftolin, F. N., & Leranth, C. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90323-t · Cited by 58
Lin, E.-J. D., Sainsbury, A., Lee, N. J., Boey, D., Couzens, M., Enriquez, R. F., Slack, K., Bland, R. J., During, M. J., & Herzog, H. (2006) · Endocrinology · doi:10.1210/en.2006-0097 · Cited by 51
Self-citationKawabe, T., Kawabe, K., & Sapru, H. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045180 · Cited by 43
Regulation of α‐Melanocyte‐Stimulating Hormone Release from Hypothalamic Neuronsa
Jégou, S., Blasquez, C., Delbende, C., Bunel, D. T., & Vaudry, H. (1993) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1993.tb19689.x · Cited by 40
Lundberg, J. M., Rudehill, A., & Sollevi, A. (1989) · European Journal of Pharmacology · doi:10.1016/0014-2999(89)90401-9 · Cited by 40
Milewicz, A., Mikulski, E., & Bidzinska, B. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801310 · Cited by 34
Lever, J. D., Mukherjee, S., Norman, D., Symons, D., & Jung, R. T. (1988) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(88)90003-3 · Cited by 34
Engel, B. T., Sato, A., & Sato, Y. (1992) · The Japanese Journal of Physiology · doi:10.2170/jjphysiol.42.549 · Cited by 17
Baranowska, B., Wolińska‐Witort, E., Martyńska, L., Chmielowska, M., Mazurczak-Pluta, T., Boguradzka, A., & Baranowska-Bik, A. (2005) · PubMed · Cited by 17
Cited by
Sorted by citations
Obesity-associated variants within FTO form long-range functional connections with IRX3
Smemo, S., Tena, J. J., Kim, K.-H., Gamazon, E. R., Sakabe, N. J., Gómez-Marín, C., Aneas, I., Credidio, F. L., Sobreira, D. R., Wasserman, N. F., et al. (2014) · Nature · doi:10.1038/nature13138 · Cited by 1,219
Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity
Timper, K., & Brüning, J. C. (2017) · Disease Models & Mechanisms · doi:10.1242/dmm.026609 · Cited by 851
Adipose tissue in control of metabolism
Luo, L., & Liu, M. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0211 · Cited by 764
Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson, M. J., & Horváth, T. L. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.026 · Cited by 453
Central Neural Regulation of Brown Adipose Tissue Thermogenesis and Energy Expenditure
Morrison, S. F., Madden, C. J., & Tupone, D. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.02.007 · Cited by 437
“Reintroduction of NPY expression in the ARC neurons of NPY / mice reduced BAT UCP1 and TBAT, as well as tyrosine hydroxylase (TH) expression in PVH and LC neurons, potentially due to NPY Y1 receptor activation in PVH (Shi et al., 2013).”
Background
Metadata
- Authors
- Shi, Y.-C., Lau, J., Lin, Z., Zhang, H., Zhai, L., Sperk, G., Heilbronn, R., Mietzsch, M., Weger, S., Huang, X.-F., Enriquez, R. F., Castillo, L., Baldock, P. A., Zhang, L., Sainsbury, A., Herzog, H., & Lin, S.
- Affiliations
- Garvan Institute of Medical Research (AU)
- Charité – Universitätsmedizin Berlin (DE)
- University of Wollongong (AU)
- The University of Sydney (AU)
- Corresponding author
- Herzog, Herbert
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-02
- Volume
- 17
- Issue
- 2
- Pages
- 236-248
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2002941555
- Cited by
- 266
- References
- 49
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 19 · 2023: 19 · 2022: 13 · 2021: 22 · 2020: 20 · 2019: 16 · 2018: 23 · 2017: 25 · 2016: 21 · 2015: 28 · 2014: 27 · 2013: 8
- FWCI
- 19.45
- Type
- journal article
- Language
- en
- Update notices
- erratum (2013-07-02)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research Online (University of Wollongong) (submittedVersion)
- The Sydney eScholarship Repository (The University of Sydney) (submittedVersion)
- Funders
- National Health and Medical Research Council (427661)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- neuropeptide Y, arcuate nucleus, paraventricular nucleus, tyrosine hydroxylase, sympathetic nervous system, brown adipose tissue, thermogenesis, UCP1, Y1 receptor, hypothalamus, locus coeruleus, energy expenditure
- MeSH terms
- Uncoupling Protein 1, Animals, Arcuate Nucleus of Hypothalamus, Adipose Tissue, Brown, Energy Metabolism, Feeding Behavior, Gene Expression Regulation, Glutamate Decarboxylase, Ion Channels, Male, Mice, Inbred C57BL, Neurons, Neuropeptide Y, Oxygen Consumption, Paraventricular Hypothalamic Nucleus, Pro-Opiomelanocortin, RNA, Messenger, Sympathetic Nervous System, Temperature, Tyrosine 3-Monooxygenase, Signal Transduction, Receptors, Neuropeptide Y, Thermogenesis, Models, Animal, Mitochondrial Proteins, Mice, Agouti-Related Protein, Diet, High-Fat
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