Cited by 266Adipose Tissue and MetabolismRegulation of Appetite and ObesityNeuropeptides and Animal Physiology

Arcuate NPY Controls Sympathetic Output and BAT Function via a Relay of Tyrosine Hydroxylase Neurons in the PVN

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Shi, Yan-Chuan, Lau, Jackie, Lin, Zhou, Zhang, Hui, Zhai, Lei, Sperk, Guenther, Heilbronn, Regine, Mietzsch, Mario +9 more·2013·Cell Metabolism

Abstract

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.

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Crossref · 10.1016/j.cmet.2013.01.006

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  • Obesity is accompanied by an increased NPY expression in the ARC.

    “Obesity is also accompanied by an increased NPY expression in the ARC.”
  • Increased NPY expression triggers a reduction in the expression of tyrosine hydroxylase neurons in the PVN of the hypothalamus and consequently diminishes the thermogenic activation of BAT and overall energy expenditure.

    “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.”

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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
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
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 › 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

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