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

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

doi:10.1016/j.cmet.2013.01.006

Cited by 214 publications

(173 citation statements)

References 51 publications

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“…TH-containing PVN neurons have been linked to the control of sympathetic outflow from the PVN (Shi et al, 2013). Thus, we examined whether TH was expressed in CRF 1 -EGFP neurons in the PVN.…”

Section: Resultsmentioning

confidence: 99%

Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

et al. 2015

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There are profound, yet incompletely understood, sex differences in the neurogenic regulation of blood pressure. Both corticotrophin signaling and glutamate receptor plasticity, which differ between males and females, are known to play important roles in the neural regulation of blood pressure. However, the relationship between hypertension and glutamate plasticity in corticotrophin-releasing hormone (CRF) receptive neurons in brain cardiovascular regulatory areas, including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN), is not understood. In the present study, we used dual label immunoelectron microscopy to analyze sex differences in slow-pressor angiotensin II (AngII) hypertension with respect to the subcellular distribution of the obligatory GluN1 subunit of the N-methyl-D-aspartate receptor (NMDAR) in the RVLM and PVN. Studies were conducted in mice expressing the enhanced green fluorescence protein (EGFP) under the control of the CRF type 1 receptor (CRF1) promoter (i.e., CRF1-EGFP reporter mice). By light microscopy, GluN1-immunoreactivity was found in CRF1-EGFP neurons of the RVLM and PVN. Moreover, in both regions tyrosine hydroxylase was found in CRF1-EGFP neurons. In response to AngII, male mice showed an elevation in blood pressure that was associated with an increase in the proportion of GluN1 on presumably functional areas of the plasma membrane in CRF1-EGFP dendritic profiles in the RVLM. In female mice, AngII was neither associated with an increase in blood pressure nor an increase in plasma membrane GluN1 in the RVLM. Unlike the RVLM, AngII-mediated hypertension had no effect on GluN1 localization in CRF1-EGFP dendrites in the PVN of either male or female mice. These studies provide an anatomical mechanism for sex-differences in the convergent modulation of RVLM catecholaminergic neurons by CRF and glutamate. Moreover, these results suggest that sexual dimorphism in AngII-induced hypertension is reflected by NMDA receptor trafficking in presumptive sympathoexcitatory neurons in the RVLM.

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Section: Resultsmentioning

confidence: 99%

Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

et al. 2015

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“…We also have confirmed that there is not a generalized activation of the hypothalamus because expression of ␦-FosB is limited almost exclusively to the sites that show an increase in p-STAT3 (6). In experiment 3 the high dose infusion of 1.2 g leptin/day increased p-STAT3 in the mArc, which has been associated with leptininduced inhibition of food intake (21) and stimulation of BAT thermogenesis (27), the DMH, which has been associated with leptin-induced stimulation of thermogenesis (31), and the VMH, which is involved in leptin-induced glucose utilization (30). These observations are consistent with the phenotype of rats receiving fourth-ventricle infusions of the three highest high doses of leptin in experiment 1.…”

Section: Discussionmentioning

confidence: 99%

Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3

Harris

Desai

2016

American Journal of Physiology-Endocrinology and Metabolism

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Previous studies have shown that very low-dose infusions of leptin into the third or the fourth ventricle alone have little effect on energy balance, but simultaneous low-dose infusions cause rapid weight loss and increased phosphorylation of STAT3 (p-STAT3) in hypothalamic sites that express leptin receptors. Other studies show that injecting high doses of leptin into the fourth ventricle inhibits food intake and weight gain. Therefore, we tested whether fourth-ventricle leptin infusions that cause weight loss are associated with increased leptin signaling in the hypothalamus. In a dose response study 14-day infusions of increasing doses of leptin showed significant hypophagia, weight loss, and increased hypothalamic p-STAT3 in rats receiving at least 0.9 μg leptin/day. In a second study 0.6 μg leptin/day transiently inhibited food intake and reduced carcass fat, but had no significant effect on energy expenditure. In a final study, we identified the localization of STAT3 activation in the hypothalamus of rats receiving 0, 0.3, or 1.2 μg leptin/day. The high dose of leptin, which caused weight loss in the first experiment, increased p-STAT3 in the ventromedial, dorsomedial, and arcuate nuclei of the hypothalamus. The low dose that increased brown fat UCP1 but did not affect body composition in the first experiment had little effect on hypothalamic p-STAT3. We propose that hindbrain leptin increases the precision of control of energy balance by lowering the threshold for leptin signaling in the forebrain. Further studies are needed to directly test this hypothesis.

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“…Neuropeptides AgRP and NPY have been shown to inhibit BAT function, while α-MSH increases SNS activity and BAT function (Shi et al, 2013; Yasuda et al, 2004). It is not known whether these circuits also control WAT browning.…”

Section: Discussionmentioning

confidence: 99%

O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat

Ruan

Dietrich

Liu

et al. 2014

Cell

237

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SUMMARY Induction of beige cells causes the browning of white fat and improves energy metabolism. However, the central mechanism that controls adipose tissue browning and its physiological relevance are largely unknown. Here we demonstrate that fasting and chemical-genetic activation of orexigenic AgRP neurons in the hypothalamus suppress the browning of white fat. O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins regulates fundamental cellular processes. The levels of O-GlcNAc transferase (OGT) and O-GlcNAc modification are enriched in AgRP neurons and are elevated by fasting. Genetic ablation of OGT in AgRP neurons inhibits neuronal excitability through the voltage-dependent potassium channel, promotes white adipose tissue browning, and protects mice against diet-induced obesity and insulin resistance. These data reveal adipose tissue browning as a highly dynamic physiological process under central control, in which O-GlcNAc signaling in AgRP neurons is essential for suppressing thermogenesis to conserve energy in response to fasting.

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

Cited by 214 publications

References 51 publications

Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension

Fourth-ventricle leptin infusions dose-dependently activate hypothalamic signal transducer and activator of transcription 3

O-GlcNAc Transferase Enables AgRP Neurons to Suppress Browning of White Fat

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