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Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN

Journal Article


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.

Authors


  •   Shi, Yan-Chuan (external author)
  •   Lau, Jackie (external author)
  •   Lin, Zhou (external author)
  •   Zhang, Hui (external author)
  •   Zhai, Lei (external author)
  •   Sperk, Guenther (external author)
  •   Heilbronn, Regine (external author)
  •   Mietzsch, Mario (external author)
  •   Weger, Stefan (external author)
  •   Huang, Xu-Feng
  •   Enriquez, Ronaldo F. (external author)
  •   Castillo, Lesley (external author)
  •   Baldock, Paul A. (external author)
  •   Zhang, Lei (external author)
  •   Sainsbury, Amanda (external author)
  •   Herzog, Herbert (external author)
  •   Lin, Shu

Publication Date


  • 2013

Citation


  • Shi, Y., Lau, J., Lin, Z., Zhang, H., Zhai, L., Sperk, G., Heilbronn, R., Mietzsch, M., Weger, S., Huang, X., Enriquez, R. F., Castillo, L., Baldock, P. A., Zhang, L., Sainsbury, A., Herzog, H. & Lin, S. (2013). Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN. Cell Metabolism, 17 (2), 236-248.

Scopus Eid


  • 2-s2.0-84873362255

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/978

Has Global Citation Frequency


Number Of Pages


  • 12

Start Page


  • 236

End Page


  • 248

Volume


  • 17

Issue


  • 2

Place Of Publication


  • United States

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.

Authors


  •   Shi, Yan-Chuan (external author)
  •   Lau, Jackie (external author)
  •   Lin, Zhou (external author)
  •   Zhang, Hui (external author)
  •   Zhai, Lei (external author)
  •   Sperk, Guenther (external author)
  •   Heilbronn, Regine (external author)
  •   Mietzsch, Mario (external author)
  •   Weger, Stefan (external author)
  •   Huang, Xu-Feng
  •   Enriquez, Ronaldo F. (external author)
  •   Castillo, Lesley (external author)
  •   Baldock, Paul A. (external author)
  •   Zhang, Lei (external author)
  •   Sainsbury, Amanda (external author)
  •   Herzog, Herbert (external author)
  •   Lin, Shu

Publication Date


  • 2013

Citation


  • Shi, Y., Lau, J., Lin, Z., Zhang, H., Zhai, L., Sperk, G., Heilbronn, R., Mietzsch, M., Weger, S., Huang, X., Enriquez, R. F., Castillo, L., Baldock, P. A., Zhang, L., Sainsbury, A., Herzog, H. & Lin, S. (2013). Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN. Cell Metabolism, 17 (2), 236-248.

Scopus Eid


  • 2-s2.0-84873362255

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers/978

Has Global Citation Frequency


Number Of Pages


  • 12

Start Page


  • 236

End Page


  • 248

Volume


  • 17

Issue


  • 2

Place Of Publication


  • United States