title: Arcuate NPY controls sympathetic output and BAT function via a relay of tyrosine hydroxylase neurons in the PVN.
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: Neuroscience Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia.
authors: Yan-Chuan
authors: YC
authors: Shi
authors: Jackie
authors: J
authors: Lau
authors: Zhou
authors: Z
authors: Lin
authors: Hui
authors: H
authors: Zhang
authors: Lei
authors: L
authors: Zhai
authors: Guenther
authors: G
authors: Sperk
authors: Regine
authors: R
authors: Heilbronn
authors: Mario
authors: M
authors: Mietzsch
authors: Stefan
authors: S
authors: Weger
authors: Xu-Feng
authors: XF
authors: Huang
authors: Ronaldo F
authors: RF
authors: Enriquez
authors: Paul A
authors: PA
authors: Baldock
authors: Lei
authors: L
authors: Zhang
authors: Amanda
authors: A
authors: Sainsbury
authors: Herbert
authors: H
authors: Herzog
authors: Shu
authors: S
authors: Lin
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D054369:Agouti-Related Protein / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D059305:Diet, High-Fat; D004734:Energy Metabolism / Q000235:genetics; D005247:Feeding Behavior; D005786:Gene Expression Regulation; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000378:metabolism; D023421:Models, Animal; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D010101:Oxygen Consumption / Q000235:genetics; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology* / Q000201:enzymology; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013564:Sympathetic Nervous System / Q000378:metabolism*; D013696:Temperature; D022722:Thermogenesis / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism*; D000071256:Uncoupling Protein 1
chemical_list: D054369:Agouti-Related Protein; D007473:Ion Channels; D024101:Mitochondrial Proteins; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; C097212:neuropeptide Y-Y1 receptor; D011333:Pro-Opiomelanocortin; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2