Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure

Li, Peng; Cui, Baiping; Zhang, Lingli; Sun, Hai-Jian; Liu, Tongyan; Zhu, Guo‐Qing

doi:10.1113/expphysiol.2012.067256

Cited by 55 publications

(50 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed that mDMHGsKO mice had reduced heart rate, but normal blood pressure. In contrast, mice with whole-brain and PVN-specific Gnas knockout have both decreased heart rate and blood pressure (9), consistent with G s α pathways in the PVN being the primary mediator of MC4R effects on blood pressure (27,39). The present results suggest that G s α signaling in different hypothalamic nuclei plays different roles in regulating cardiovascular function.…”

Section: Discussionmentioning

confidence: 37%

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations

Chen

Shrestha

Podyma

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 37%

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations

Chen

Shrestha

Podyma

et al. 2016

Journal of Clinical Investigation

View full text Add to dashboard Cite

“…In the mouse DMH, we observed a significant number of RVLM-projecting neurons; however, the number was far smaller than when the CtB injections encompassed the raphe pallidus significant decreases in SNA, MAP, and HR, because NPY inhibits a G protein-activated inwardly rectifying K (GIRK) current (39-41), which can hyperpolarize to a greater extent than GABA A receptors, which open Cl channels. While the limited inhibition by GABA was expected, the effect of PVN AgRP on SNA in rats is controversial (8,42). Here, we show that doses of PVN AgRP that exceed those required to elicit food intake and sufficient to decrease body temperature failed to decrease SSNA, AP, or HR.…”

Section: Discussionmentioning

confidence: 76%

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Shi¹,

Madden²,

Brooks³

2017

Journal of Clinical Investigation

View full text Add to dashboard Cite

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 6 9 jci.org Volume 127 Number 7 July 2017We next tested whether selective excitation or inhibition of ArcN NPY/AgRP neurons alters splanchnic SNA (SSNA), mean AP (MAP), or heart rate (HR) ( Figure 1). As shown in representative experiments ( Figure 1, A and B) and grouped data ( Figure 1C), in ArcN hM3Dq mice, i.p. CNO (0.3 mg/kg) promptly decreased SSNA, MAP, and HR, whereas i.p. saline had no effects. The suppression induced by CNO was sustained for at least 1 hour, and, in mice with longer recordings, up to 4 hours (data not shown). In rats, guinea pigs, and humans, CNO can have nonspecific effects due to its conversion to clozapine (17, 18). However, in WT mice receiving the Cre-dependent hM3Dq vector, neither i.p. saline nor CNO significantly altered these variables, suggesting that CNO was not exerting its effects independently of DREADD activation. A separate group of Agrp-IRES-Cre mice instead received AAV-hM4Di-mCherry in the ArcN (Figure 1, D-F). In these ArcN hM4Di mice, i.p. CNO (0.3 and 1 mg/kg) dose-dependently increased SSNA, MAP, and HR, although the responses developed both NPY-GFP and Cre in AgRP neurons. In agreement with an earlier study using a different approach (14), we found that while not all NPY-GFP neurons had visible hM3Dq-mCherry labeling, 100% of the hM3Dq-mCherry-marked neurons also expressed NPY-GFP (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI92008DS1). WT mice never expressed the Cre-dependent DREADD. In a second set of experiments, 2 or more weeks after Agrp-IRES-Cre mice received hM3Dq bilaterally in the ArcN, CNO (0.3 mg/kg) or the saline vehicle was administered i.p., and food intake was monitored for the following 4 hours. As shown previously (14), i.p. CNO, but not saline, rapidly evoked food intake in ArcN hM3Dq mice (Supplemental Figure 1). Conversely, activation of inhibitory DREADDs in ArcN hM4Di mice at the beginning of the feeding period (lights out) inhibited food intake (Supplemental Figure 1). Therefore, we anatomically and functionally confirm that this approach selectively targets ArcN NPY/AgRP neurons. The Journal of Clinical Investigation R E S E A R C H A R T I C L E2 8 7 0jci.org Volume 127 Number 7 July 2017neurons were also observ...

show abstract

“…This AAR has been extended recently to other WAT pads, but with renal sympathetic nerve activity increases (adipose afferent renal reflex, AARR) with related changes in blood pressure and other cardiovascular responses (19,22,35,42,55,66,67).…”

Section: R896mentioning

confidence: 99%

Short and long sympathetic-sensory feedback loops in white fat

Ryu

Bartness

2014

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129ϩPRV152-colocalized neurons (ϳ50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (Ͼ60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions.herpes simplex virus; pseudorabies virus; Siberian hamsters; sympathetic nervous system; sensory system; white adipose tissue WE PREVIOUSLY DEMONSTRATED postganglionic sympathetic nervous system (SNS) innervation of inguinal and epididymal white adipose tissue [IWAT and EWAT, respectively;(69)] and together with others determined that the pattern of SNS drive is fat pad-specific (15,29,43). Collectively, these and other data such as the blockade of lipolysis with WAT SNS denervation (for review see Refs. 8 and 9) establish that activation of the SNS innervation of WAT is the principal mechanism underlying lipid mobilization. To unravel the central nervous system (CNS) origins controlling the sympathetic drive to WAT, we used the retrograde transneuronal tract tracer pseudorabies virus (PRV) Bartha's K strain to define the CNS origins of the sympathetic outflow to IWAT and EWAT in Siberian hamsters as well as in Sprague-Dawley rats (4). We and others expanded these studies not only for subcutaneous WAT and the retroperitoneal WAT (RWAT) depot (1, 13, 52, 57) but also for true visceral WAT (mesenteric WAT; see Ref. 46). It is noteworthy that the SNS components responsible for sympathetic outflow to the aforementioned fat pads share many central sites in the circuit...

show abstract

Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure

Cited by 55 publications

References 47 publications

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations

Gsα deficiency in the dorsomedial hypothalamus underlies obesity associated with Gsα mutations

Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways

Short and long sympathetic-sensory feedback loops in white fat

Contact Info

Product

Resources

About