ライフサイエンスコーパス: POMC

1 POMC and AGRP neurons, respectively, agonize and antagon

2 POMC neurons receive orexin-A (OX-A)-expressing inputs a

3 (POMC) neurons and ODN selectively activated POMC neurons through the ODN-GPCR but not GABAA, and sup

4 ption factors Prdm12 in developing and adult POMC neurons.

5 owever, specific deletion of Prdm12 in adult POMC neurons showed that it is no longer required for Po

6 Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant

7 This novel mechanism of ER stress affecting POMC processing in DIO highlights the importance of ER s

8 Scn9a deletion in AGRP, POMC, or paraventricular hypothalamic neurons reduced EP

9 data suggest a potential role for NPY, AGRP, POMC, and CART in regulating energetic status in A. burt

10 MC neurons of the offspring prevents altered POMC projections to the preautonomic paraventricular nuc

11 sent in comparably significant numbers among POMC neurons.

12 10(-)(9)), GNPDA2 (P = 1.11 x 10(-)(8)) and POMC (P = 4.94 x 10(-)(8)) as well as a potential second

13 ually worsened glucose tolerance in AgRP and POMC IR KO mice and their respective controls but increa

14 us, including distinct responses in AgRP and POMC neuron subtypes.

15 Although AgRP and POMC neurons in the hypothalamus have long been associat

16 isualize long-range connectivity of AGRP and POMC neurons in the mouse, two molecularly defined hypot

17 uggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors acro

18 These data reveal that AgRP and POMC neurons receive real-time information about the ava

19 tracing experiments showed that NPY/AgRP and POMC neurons were minimally affected by the knockout.

20 ell types that control food intake, AgRP and POMC neurons, in awake behaving mice.

21 ormoglycaemic and diabetic AgRP-ires-cre and POMC-cre mice to chemogenetically activate or inhibit th

22 ose homeostasis, adiposity, hyperphagia, and POMC neuronal projections, all of which are ameliorated

23 ated genes include FERMT3, ITGAM, ITGAX, and POMC In summary, applying an integrative multiomics appr

24 vity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and

25 n-specifically depolarizes both AgRP/NPY and POMC neurons but a strong inhibitory input to POMC neuro

26 ssels and neurons, and in particular NPY and POMC neurons in the arcuate nucleus.

27 , urocortin, proopiomelanocortin (POMC), and POMC-derived peptides.

28 at least in part, by inhibiting anorexigenic POMC neurons remains unclear.

29 nic AgRP neurons and inhibiting anorexigenic POMC neurons.

30 bitory synaptic input to nearby anorexigenic POMC neurons.

31 The inhibition of anorexigenic POMC neurons may be one mechanism underlying the orexige

32 decreasing the activity of the anorexigenic POMC neurons.

33 subsequently adopt either the anorexigenic (POMC) or the orexigenic (NPY/AgRP) identity remains elus

34 We show that, in rodents, another POMC-derived peptide, beta-endorphin, is coordinately sy

35 (ARC) in hypothalamus contains antagonizing POMC and AGRP/NPY neurons for negative and positive ener

36 ber, but not the magnitude, of activated ARC POMC neurons and is of therapeutic relevance to obesity

37 1 is an obesity suppression mechanism in ARC POMC neurons and HFD-AMPK inhibits this mechanism by pho

38 , insulin-induced hypoglycemia increases ARC POMC neuron activity.

39 tiate the firing frequency of individual ARC POMC-EGFP cells compared with agonists alone.

40 a indicate a functional heterogeneity of ARC POMC neurons by revealing distinct subpopulations of POM

41 Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic paras

42 onto two of their postsynaptic targets (Arc POMC and paraventricular nucleus neurons), where ATP dra

43 However, unlike ARC(AgRP) neurons, ARC(POMC) neurons are extremely slow in affecting hunger (ma

44 Pro-opiomelanocortin (ARC(POMC)) neurons are viewed as the counterpoint to ARC(AgR

45 >PVH(MC4R) synapse is potentiated by the ARC(POMC) neuron-derived MC4R agonist, alpha-melanocyte stim

46 ons expressing oxytocin receptor, unlike ARC(POMC) neurons, rapidly cause satiety when chemo- or opto

47 show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and in

48 some endocrine cells are generated, such as POMC-positive cells in the intermediate lobe.

49 We report that OX-A/OX-1R signaling at POMC neurons promotes 2-AG biosynthesis, hyperphagia, an

50 nal populations that mediate energy balance (POMC and AgRP neurons), but also into neurons critical f

51 several stress-responsive genes (e.g., CRF, POMC, and FKBP5) is altered in the PFC of AUD subjects.

52 impact of amylin/calcitonin signaling in CTR-POMC neurons on energy metabolism and demonstrate the ne

53 ocessing in the majority of Nscl-2-deficient POMC neurons had no effect on energy homeostasis.

54 In developing POMC neurons, abnormal cilia formation disrupts axonal p

55 we profiled the transcriptomes of developing POMC and NPY/AgRP neurons in mice.

56 Selective ablation of Prdm12 in embryonic POMC neurons led to significantly reduced Pomc expressio

57 gnalling is increased, resulting in enhanced POMC mRNA induction.

58 strate that serotonin 2C receptor-expressing POMC neurons are required to control energy and glucose

59 (AgRP) and pro-opiomelanocortin-expressing (POMC) neurons; however, it is unknown whether activity o

60 In brains with low-level expression, POMC mRNA and protein was largely confined to a populati

61 In brains with high-level expression, POMC mRNA and protein was observed in the vast majority

62 First, POMC mRNA and precursor protein expression in non-neuron

63 , the anorexigenic neuropeptide alphaMSH for POMC-neurons, and two growth-stimulatory peptides, growt

64 Selective Nkx2.1 ablation from POMC neurons decreased Pomc expression in adult males an

65 calcitonin receptor (CTR), was depleted from POMC neurons using an inducible mouse model.

66 thermore, conditional Isl1 inactivation from POMC neurons impairs Pomc expression, leading to hyperph

67 neurons did not affect sIPSCs recorded from POMC neurons.

68 ely to cause a decrease in GABA release from POMC neurons.

69 functional consequence of GABA released from POMC neurons in terms of the regulation of normal energy

70 ugh the release of peptide transmitters from POMC neurons is regulated by energy state, whether simil

71 in addition to the peptide transmitters from POMC neurons.

72 t establishes and maintains fully functional POMC neurons remains to be explored.

73 ucose and leptin signalling in glutamatergic POMC neurons is critical for determining the strength of

74 spatiotemporal pattern whereby low and high POMC syntheses in tanycytes occur periodically in each b

75 Thus, understanding how POMC neurons integrate these two signal molecules at the

76 her sex that recapitulates symptoms of human POMC deficiency.

77 ctor NKX2.1 is present in mouse hypothalamic POMC neurons from early development to adulthood.

78 Although the relevance of hypothalamic POMC neurons in the regulation of body weight and energy

79 Although the pathophysiology of hypothalamic POMC neurons is well understood, the genetic program tha

80 ive reporter gene expression to hypothalamic POMC neurons in transgenic mice and zebrafish.

81 in the arcuate nucleus of the hypothalamus (POMC(ARH) neurons) associated with decreased neural acti

82 energy and glucose homeostasis and implicate POMC neurons as the target for the effect of serotonin 2

83 Abrogating insulin action in POMC neurons of the offspring prevents altered POMC proj

84 cent work indicates that calcium activity in POMC cells changes in response to food cues on times sca

85 Conversely, decreased activity in POMC cells is associated with increased food intake and

86 BAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals

87 e we show that inhibition of ciliogenesis in POMC-expressing developing hypothalamic neurons, by depl

88 ochondria- endoplasmic reticulum contacts in POMC neurons during diet-induced obesity.

89 To the contrary, in POMC IR KO mice, insulin lowered hGP but failed to suppr

90 The loss of CTR in POMC neurons leads to increased body weight gain, increa

91 A (1 or 5 mum) induces an outward current in POMC neurons that is reversed by the highly selective mu

92 ve agonist DAMGO induced outward currents in POMC neurons that were completely reversed by a relative

93 ption of the BBSome by Bbs1 gene deletion in POMC or AgRP neurons increases body weight and adiposity

94 contrast, adult-onset ciliary dysgenesis in POMC neurons causes no significant change in adiposity.

95 ontaining factor 12 (Prdm12) was enriched in POMC neurons but absent in NPY/AgRP neurons.

96 restraint stress altered Gad1 expression in POMC neurons.

97 hat obesity in mice lacking the Bbs1 gene in POMC neurons is associated with hyperphagia.

98 ndent deterioration of Ca(2+) homeostasis in POMC neurons during obesity development resulting in imp

99 gic recordings and GCaMP6f Ca(2+) imaging in POMC neurons in mouse brain slices indicate that maximal

100 This paradoxical increase in POMC activity was crucial for CB1R-induced feeding, beca

101 demonstrated when Htr2c loss was induced in POMC neurons in adult mice using a tamoxifen-inducible P

102 RP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron f

103 HIF2alpha knockout in POMC neurons led to age-dependent excess weight gain and

104 The data show that somatic MORs in POMC neurons couple to multiple effectors that have diff

105 , the data show that somatodendritic MORs in POMC neurons inhibit neuronal activity through at least

106 Prolonged activation of somatic MORs in POMC neurons robustly inhibited action potential firing

107 on was used to detect vGlut2 and Gad mRNA in POMC neurons during early postnatal development.

108 ge of POMC neurons expressing vGlut2 mRNA in POMC neurons progressively decreased from approximately

109 ybridization to detect Gad1 and Gad2 mRNA in POMC neurons, as these encode the glutamate decarboxylas

110 ncreased hepatic triglyceride levels only in POMC IR KO mice, consistent with impaired lipolytic regu

111 pening by the PI3K-PLC signalling pathway in POMC neurons enhances spontaneous GABA release via activ

112 sis downstream of the leptin-PI3K pathway in POMC neurons.

113 h control animals, mice lacking PPARgamma in POMC neurons had increased energy expenditure and locomo

114 Furthermore, ablation of PPARgamma in POMC neurons preserved the interaction between mitochond

115 rn stimulate mitochondrial ATP production in POMC neurons, promoting mitochondrial fusion in their ne

116 A requirement of serotonin 2C receptors in POMC neurons for the maintenance of normal energy and gl

117 tin (POMC) neurons; whether the reduction in POMC neuronal function is secondary to the microglial ac

118 ing glucose metabolism, insulin signaling in POMC neurons controls adipose tissue lipolysis and preve

119 he physiological role of amylin signaling in POMC neurons, the core component of the amylin receptor,

120 re responsible for the majority of sIPSCs in POMC neurons as well as the fasting-induced increase in

121 receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, a

122 GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release

123 le to activate ERK signaling specifically in POMC neurons independently of leptin.

124 omised in mice lacking SIRT1 specifically in POMC neurons.

125 ha secretion induces mitochondrial stress in POMC neurons that contributes to the development of obes

126 Thus, in POMC cells, the decline in the GIRK current during prolo

127 ce regulation, genetic deletion of vGlut2 in POMC neurons was accomplished using Cre-lox technology.

128 Male, but not female, mice lacking vGlut2 in POMC neurons were unable to maintain energy balance to t

129 iture accompanied by lower NPY and increased POMC mRNA levels.

130 ial fusion in their neurites, and increasing POMC neuronal firing rates and excitability.

131 ns in adult mice using a tamoxifen-inducible POMC-cre system.

132 d with channelrhodopsin AgRP neurons inhibit POMC neurons through GABA-mediated transmission.

133 These results suggest that Dyn-A inhibits POMC neurons through activation of the (kappa)2 opioid r

134 spite their opposing actions on food intake, POMC and NPY/AgRP neurons in the arcuate nucleus of the

135 Second, unlike other known POMC-expressing cells, tanycytes rarely contained detect

136 ed the transcriptomes of genetically labeled POMC and NPY/AgRP neurons in the developing mouse hypoth

137 had low-, 9 intermediate-, and 15 high-level POMC expression in tanycytes.

138 ockout mice and in mice lacking p53-mediated POMC induction in epidermal keratinocytes.

139 ation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to cha

140 mbined agonists activated significantly more POMC neurons (46%) compared with either drug alone ( app

141 llular activity via calcium imaging in mouse POMC-EGFP brain slices, which revealed that combined ago

142 pe and maintains a fully functional neuronal POMC phenotype throughout adulthood remains unknown.

143 Here we characterized this non-neuronal POMC expression in detail using in situ hybridization an

144 tant role for GABAergic projections from non-POMC non-AgRP neurons to the paraventricular hypothalami

145 n of GABA release from a major subset of non-POMC, non-AgRP GABAergic neurons in the hypothalamus.

146 hat JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic re

147 7 was only expressed in approximately 10% of POMC neurons at day 1 and increased until approximately

148 In mice, approximately 43% of POMC neurons contained VGLUT2, and 54% contained GAD67 m

149 y 1 and increased until approximately 45% of POMC neurons coexpressed Gad67 at 8 weeks of age.

150 In rats, approximately 58% of POMC neurons were labeled for VGLUT2 and 37% for GAD67 m

151 ockdown of HIF-1alpha impairs the ability of POMC neurons to adapt to the changing metabolic environm

152 In contrast, absence of POMC processing in the majority of Nscl-2-deficient POMC

153 ishes, whereas DREADD-mediated activation of POMC neurons enhances CB1R-driven feeding.

154 on of these cells promotes the activation of POMC neurons upon HFD exposure, reduces feeding, and pro

155 ctivation also promotes neuronal activity of POMC cells.

156 rients and hormones modulate the activity of POMC neurons over protracted periods of time.

157 mice is paralleled by decreased activity of POMC neurons.

158 r, biological, and functional adaptations of POMC neurons to HFD, thereby regulating whole-body energ

159 D feeding during lactation, the formation of POMC and AgRP projections to hypothalamic target sites i

160 The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal gluc

161 and elucidate the physiologic importance of POMC in tanycytes.

162 nsible for increased GABAergic inhibition of POMC cells during fasting, likely mediated through incre

163 n POMC neurons, leading to the inhibition of POMC neuron firing.

164 These data suggest that direct inhibition of POMC neurons by Dyn A is mediated through the MOR, not t

165 In contrast to the strong inhibition of POMC neurons by Dyn-A, we found a weaker direct inhibito

166 signer-drugs (DREADD)-mediated inhibition of POMC neurons diminishes, whereas DREADD-mediated activat

167 Notably, the inhibition of POMC neurons stimulated feeding while decreasing glucose

168 lysis revealed Cadm1-positive innervation of POMC neurons via afferent projections originating from b

169 We particularly showed an innervation of POMC, AgRP, MCH and ORX neurons by the dorsomedial and d

170 nt results show that the GABAergic nature of POMC neurons can be dynamically regulated by energy stat

171 se genetic models to selective ablate one of POMC-neuron enriched transcription factors Prdm12 in dev

172 ction significantly reduce the percentage of POMC neurons expressing Gad1 mRNA in both male and femal

173 The percentage of POMC neurons expressing vGlut2 mRNA in POMC neurons prog

174 triction, whether the GABAergic phenotype of POMC neurons is also regulated in an energy-state-depend

175 results show that the GABAergic phenotype of POMC neurons is decreased selectively by caloric deficit

176 , suggesting that the GABAergic phenotype of POMC neurons is particularly sensitive to energy deficit

177 The fact the GABAergic phenotype of POMC neurons is sensitive to energy state suggests a dyn

178 ic, surprisingly, only a small population of POMC neurons has been found to be glutamatergic, and a s

179 structs the post-translational processing of POMC by decreasing proconverting enzyme 2, which catalyz

180 neurons, and posttranslational processing of POMC remain unaffected in response to maternal HFD feedi

181 neurons, electrophysiological properties of POMC neurons, and posttranslational processing of POMC r

182 results reveal that GPR45 is a regulator of POMC signaling and energy expenditure, which suggests th

183 lts uncover a previously unsuspected role of POMC neurons in the promotion of feeding by cannabinoids

184 receptor would lead to a new steady state of POMC neuron activity reflecting the sustained GIRK curre

185 rons by revealing distinct subpopulations of POMC cells activated by 5-HT2CRs and disinhibited by 5-H

186 A small subset of POMC neurons appears to have a dual AA phenotype based o

187 iew and discuss the current understanding of POMC neurons from their development and intracellular re

188 ly, our findings indicate that the GLP-1R on POMC/CART-expressing ARC neurons likely mediates liraglu

189 icate a direct inhibitory effect of Dyn-A on POMC neurons through activation of the (kappa)2 opioid r

190 rectifying potassium (GIRK)-like channels on POMC neurons.

191 actions of the antagonist at MORs located on POMC neurons.

192 ay regulates the inhibitory effect of MCH on POMC expression.

193 OR-2-selective agonist GR89696 binds MORs on POMC neurons but fails to induce an outward current.

194 portion of spontaneously released GABA onto POMC cells and are responsible for increased GABAergic i

195 contribute spontaneously released GABA onto POMC neurons, although when activated with channelrhodop

196 itry conveys inhibitory neuromodulation onto POMC cells that is sensitive to the animal's energy stat

197 The presynaptic responses onto POMC neurons, and the expression of tdTomato in AgRP-NPY

198 frequency of spontaneous IPSCs (sIPSCs) onto POMC neurons increases during caloric deficits.

199 The arcuate pro-opiomelanocortin (POMC) neurons in particular have been shown to be critic

200 ted protein (AgRP) and pro-opiomelanocortin (POMC) neurons in regulating hepatic and adipose tissue i

201 Hypothalamic pro-opiomelanocortin (POMC) neurons promote satiety.

202 ARC TH cells inhibited pro-opiomelanocortin (POMC) neurons through synaptic mechanisms.

203 ding satiety-promoting pro-opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking.

204 arcuate nucleus (ARC) pro-opiomelanocortin (POMC) neurons, which are also disinhibited through a 5-H

205 er of appetite-curbing pro-opiomelanocortin (POMC) neurons; whether the reduction in POMC neuronal fu

206 AgRP) and anorexigenic pro-opiomelanocortin (POMC) neuropeptides.

207 ucose homeostasis, and pro-opiomelanocortin (POMC) projections.

208 ted peptide (AgRP) and pro-opiomelanocortin (POMC) subtypes, and an orexigenic somatostatin neuron po

209 Pro-opiomelanocortin (POMC)- and agouti-related peptide (AgRP)-expressing neur

210 gnaling (anorexigenic) pro-opiomelanocortin (POMC)-expressing and hunger signaling (orexigenic) agout

211 Satiety-signaling, pro-opiomelanocortin (POMC)-expressing neurons in the arcuate nucleus of the h

212 ces no net response in pro-opiomelanocortin (POMC)-expressing neurons.

213 eus (Arc), containing pro-opoiomelanocortin (POMC), neuropeptide Y (NPY) and growth hormone releasing

214 veral hypothalamic nuclei but not in AgRP or POMC neurons.

215 from well-defined feeding regulatory AgRP or POMC neurons.

216 ase in genes encoding anorexigenic peptides, POMC, and somatostatin may account for the reduced body

217 indicate that in addition to their peptides, POMC neurons can release either the amino acid (AA) tran

218 igh-fat diet also did not affect the portion POMC neurons expressing Gad1, suggesting that the GABAer

219 ynaptic GABAergic terminals and postsynaptic POMC neurons.

220 ulation of hypothalamic microglia to promote POMC neuronal activation in association with hypothalami

221 Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus

222 Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus

223 rison, we also analyzed Proopiomelanocortin (POMC)-expressing neurons, an intermingled population tha

224 egulator 1 (NEGR1), and proopiomelanocortin (POMC)] by PUFAs, only 125 genes [e.g., adiponectin, C1Q

225 ression of anorexigenic proopiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP) neuro

226 on or near anorexigenic proopiomelanocortin (POMC) cells.

227 sis by the anorexigenic proopiomelanocortin (POMC) neurons and orexigenic agouti-related peptide (AgR

228 downstream anorexigenic proopiomelanocortin (POMC)-positive neurons in a GABA-dependent manner, which

229 arcuate nucleus (ARC), proopiomelanocortin (POMC) neurons and the POMC-derived peptide alpha-melanoc

230 Arcuate proopiomelanocortin (POMC) neuron-specific deletion of Ptpn1 causes a similar

231 ts in the gene encoding proopiomelanocortin (POMC) have extreme early-onset obesity, hyperphagia, hyp

232 luding those expressing proopiomelanocortin (POMC) and agouti-related peptides (AgRP).

233 d in neurons expressing proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript

234 e groups neurons [e.g., proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons], and as

235 Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of e

236 Hypothalamic proopiomelanocortin (POMC) neurons are important regulators of energy balance

237 ization in hypothalamic proopiomelanocortin (POMC) neurons as these neurons produce the endogenous op

238 (MORs) in hypothalamic proopiomelanocortin (POMC) neurons leads to the activation of G-protein-coupl

239 Hypothalamic proopiomelanocortin (POMC) neurons release peptide products that potently inh

240 EY POINTS: Hypothalamic proopiomelanocortin (POMC) neurons release peptide products that potently inh

241 driver of hypothalamic proopiomelanocortin (POMC) neurons.

242 C isoform Pkc-lambda in proopiomelanocortin (POMC) neurons disrupts leptin action, reduces melanocort

243 amic neurons, including proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, also re

244 amic neurons, including proopiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons, also re

245 lamic neurons including proopiomelanocortin (POMC)-producing neurons regulate body weights.

246 intake and to increase proopiomelanocortin (POMC) gene expression in the hypothalamus.

247 KOR), directly inhibits proopiomelanocortin (POMC) neurons in the hypothalamus through activation of

248 thalamic neuron markers proopiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AGR

249 of PPARgamma in murine proopiomelanocortin (POMC) neurons decreases peroxisome density, elevates rea

250 orexigenic neuropeptide proopiomelanocortin (POMC).

251 STATEMENT Activation of proopiomelanocortin (POMC) cells signals satiety, whereas GABAergic cells in

252 d increased activity of proopiomelanocortin (POMC) neurons.

253 f its precursor protein proopiomelanocortin (POMC) remained unaltered.

254 MCH reduces proopiomelanocortin (POMC) neuronal activity, and the SIRT1/FoxO1 pathway reg

255 f the stress regulatory proopiomelanocortin (POMC) neuron-producing beta-endorphin peptides in the hy

256 eratinocytes synthesize proopiomelanocortin (POMC) that is processed to melanocyte-stimulating hormon

257 abies virus showed that proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons in the a

258 generally believed that proopiomelanocortin (POMC) is expressed exclusively by neurons in the adult r

259 us was observed for the proopiomelanocortin (POMC; rho = -0.632, P = 4.70 x 10(-27)) gene.

260 study on afferences to proopiomelanocortin (POMC), agouti-related peptide (AgRP), melanin-concentrat

261 rmone (CRH), urocortin, proopiomelanocortin (POMC), and POMC-derived peptides.

262 te food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding.

263 ving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding.

264 H) and colocalized with proopiomelanocortin (POMC) in the arcuate nucleus (ARC).

265 rved in apposition with proopiomelanocortin (POMC) neurons and ODN selectively activated POMC neurons

266 AgRP) and anorexigenic (proopiomelanocortin; POMC) neurons via an ATP-dependent mechanism.

267 ) show that hypothalamic propiomelanocortin (POMC) neurons innervate the anterior ventral V-SVZ and r

268 stically, we determined that GPR45 regulates POMC expression via the JAK/STAT pathway in a cell-auton

269 ion in expression of the metabolic regulator POMC and less energy expenditure prior to the onset of o

270 These neurons release POMC-encoded melanocortins, which are potent anorexigeni

271 bd7 mRNA is expressed and translated by some POMC and GABAergic-neurons in the hypothalamic arcuate n

272 emains poorly studied.SIGNIFICANCE STATEMENT POMC and NPY/AgRP neurons are derived from the same hypo

273 ices revealed that GLP-1 directly stimulates POMC/CART neurons and indirectly inhibits neurotransmiss

274 hibited anorexigenic neurons that synthesize POMC, as determined by whole cell recording.

275 erably more sensitive to energy deficit than POMC neurons.

276 We hypothesize that POMC and NPY/AgRP cell fates are specified and maintaine

277 Altogether, the results indicate that POMC neurons are largely glutamatergic early in life and

278 We further revealed that POMC(ARH) neurons project to the VTA and provide an inhi

279 , proopiomelanocortin (POMC) neurons and the POMC-derived peptide alpha-melanocyte-stimulating hormon

280 well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 x 10(-)(5) after conditio

281 the brain melanocortin system, including the POMC-MC4R pathway, a mechanism also activated by leptin

282 inistration of melanotan-2, an analog of the POMC derivative alpha-MSH, suppressed adult obesity in G

283 Finally, we show that photoinhibition of the POMC(ARH)->VTA circuit in mice increases body weight and

284 esent a major functional division within the POMC cell group.

285 dings indicate that the relevance of AgRP to POMC neuron GABA connectivity depends on the state of Ag

286 e relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need t

287 OMC neurons but a strong inhibitory input to POMC neurons balances the excitation.

288 bute to the strong spontaneous GABA input to POMC neurons.

289 nificant source of spontaneous GABA input to POMC neurons.

290 ated glutamate and GABA neurotransmission to POMC neurons.

291 show that leptin's action on GABA release to POMC neurons is influenced by glucose levels.

292 vely these data provide evidence that DMH-to-POMC GABA circuitry conveys inhibitory neuromodulation o

293 e probability of GABA is increased at DMH-to-POMC synapses following an overnight fast.

294 ning the strength of inhibitory tone towards POMC neurons.

295 ivo, we tracked these cells using transgenic POMC-EGFP mice or by retroviral expression of GFP.

296 conditions of undernourishment, during which POMC neuronal activity is decreased.

297 cuitry and provide a mechanism through which POMC neurons could be inhibited, or disinhibited, rapidl

298 energic receptors in NPY/AgRP neurons, while POMC neurons are inhibited via alpha2A - adrenergic rece

299 or failed to affect food intake of mice with POMC-specific PPARgamma ablation.

300 -dependent glucose lowering mechanism within POMC neurons is a potential target for the development o