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

Yan-Chuan Shi; Jackie Lau; Zhou Lin; Hui Zhang; Lei Zhai; Guenther Sperk; Regine Heilbronn; Mario Mietzsch; Stefan Weger; Xu-Feng Huang; Ronaldo F Enriquez; Paul A Baldock; Lei Zhang; Amanda Sainsbury; Herbert Herzog; Shu Lin

doi:10.1016/j.cmet.2013.01.006

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

Cell Metab. 2013 Feb 5;17(2):236-48. doi: 10.1016/j.cmet.2013.01.006.

Authors

Yan-Chuan Shi¹, Jackie Lau, Zhou Lin, Hui Zhang, Lei Zhai, Guenther Sperk, Regine Heilbronn, Mario Mietzsch, Stefan Weger, Xu-Feng Huang, Ronaldo F Enriquez, Paul A Baldock, Lei Zhang, Amanda Sainsbury, Herbert Herzog, Shu Lin

Affiliation

¹ Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.

PMID: 23395170
DOI: 10.1016/j.cmet.2013.01.006

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, Brown / metabolism*
Agouti-Related Protein / metabolism
Animals
Arcuate Nucleus of Hypothalamus / cytology
Arcuate Nucleus of Hypothalamus / metabolism*
Diet, High-Fat
Energy Metabolism / genetics
Feeding Behavior
Gene Expression Regulation
Glutamate Decarboxylase / metabolism
Ion Channels / metabolism
Male
Mice
Mice, Inbred C57BL
Mitochondrial Proteins / metabolism
Models, Animal
Neurons / cytology
Neurons / enzymology*
Neuropeptide Y / genetics
Neuropeptide Y / metabolism
Oxygen Consumption / genetics
Paraventricular Hypothalamic Nucleus / cytology*
Paraventricular Hypothalamic Nucleus / enzymology
Pro-Opiomelanocortin / genetics
Pro-Opiomelanocortin / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Neuropeptide Y / metabolism
Signal Transduction / genetics
Sympathetic Nervous System / metabolism*
Temperature
Thermogenesis / genetics
Tyrosine 3-Monooxygenase / genetics
Tyrosine 3-Monooxygenase / metabolism*
Uncoupling Protein 1

Substances

Agouti-Related Protein
Ion Channels
Mitochondrial Proteins
Neuropeptide Y
RNA, Messenger
Receptors, Neuropeptide Y
Ucp1 protein, mouse
Uncoupling Protein 1
neuropeptide Y-Y1 receptor
Pro-Opiomelanocortin
Tyrosine 3-Monooxygenase
Glutamate Decarboxylase
glutamate decarboxylase 2