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

YC Shi, J Lau, Z Lin, H Zhang, L Zhai, G Sperk… - Cell metabolism, 2013 - cell.com
YC Shi, J Lau, Z Lin, H Zhang, L Zhai, G Sperk, R Heilbronn, M Mietzsch, S Weger…
Cell metabolism, 2013cell.com
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 …
Summary
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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