ライフサイエンスコーパス: leptin

1 active protein) and adipokines (adiponectin, leptin).

2 esity that can be mitigated by administering leptin.

3 abolishes the antidepressant-like effects of leptin.

4 ic transcription of the Bdnf gene induced by leptin.

5 lete backbone resonance assignments of human leptin.

6 GT inhibition, iron did not further decrease leptin.

7 ways including O-GlcNAcylation also regulate leptin.

8 nction which is driven, at least in part, by leptin.

9 ck phosphorus (PG-BP) composite to detect of leptin.

10 and cord blood glucose, insulin, lipids, and leptin.

11 individuals suggesting a saturable effect of leptin.

12 t Tyr-1325 are responsible for the effect of leptin.

13 increases in selected measures of lipids and leptin.

14 pecifically in POMC neurons independently of leptin.

15 sizes were seen with human milk insulin and leptin (0.24 z-score units and 0.37-1.15 FMI units per u

16 There were no significant differences in leptin (-0.7 ng/mL; -2.1, 0.8 ng/mL) or fasting glucose

17 ial redox state (+167%) and decreased plasma leptin (-45%) and triiodothyronine (-21%) concentrations

18 findings suggest a novel mechanism by which leptin, acting in the NTS, could potentiate gastrointest

19 These findings indicate that leptin, acting via an AKT-p300 HAT epigenetic cascade, i

20 This leptin action was reduced by Janus kinase inhibitor (AG4

21 degree of leptin sensitization and improved leptin action, both centrally and peripherally.

22 impact energy balance via the modulation of leptin action.

23 Mechanistic experiments disclosed that leptin activates signal transducer and activator of tran

24 xcitatory neurotransmission, suggesting that leptin acts cell autonomously to suppress representation

25 However, little was known about how leptin acts in the NTS neurons to inhibit food intake.

26 Our results suggest that leptin acts in the NTS to reduce food intake by increasi

27 Whether leptin acts in the paraventricular nucleus (PVN) to incr

28 L6, IL18, IL1 receptor antagonist, TNFalpha, leptin, adiponectin, fibrinogen, and plasminogen activat

29 terol, glucose, insulin, insulin resistance, leptin, adiponectin, resistin, liver function enzymes, f

30 that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of ob

31 We demonstrate that short-term leptin administration alters food intake during refeedin

32 Furthermore, chronic leptin administration reverses these abnormalities in ad

33 Leptin also increased the size of evoked EPSPs and the a

34 the last session, plasma levels of insulin, leptin, amylin, and glucagon-like peptide-1 (GLP-1) were

35 nt by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregul

36 adipokines and inflammatory markers such as leptin and C-reactive protein), and 24 were higher in me

37 Taken together, these results suggest that leptin and CCK receptors may both contribute to short-te

38 n mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for ext

39 TL1A and TRAIL expression in hVAT and higher leptin and IL6 serum concentrations, diabetes status, an

40 ed to 1.5-2.5 times higher concentrations of leptin and insulin compared with infants of NW mothers.

41 E), leading to obesity, along with increased leptin and insulin levels and HOMA.

42 tolerance and antioxidant capacity, reduced leptin and insulin, and increased adiponectin in HFD off

43 ne regulators of energy metabolism including leptin and insulin, and microbiome) and brain circuitrie

44 Although in past decades the adipokine leptin and its own receptor have been considered as sign

45 Therefore, leptin and leptin receptor concentrations from 3068 sibl

46 o-inflammatory adipokine secretions, such as leptin and oestrogen secretions.

47 , a positive association between circulating leptin and PCSK9 levels was found only when the body mas

48 The proinflammatory leptin and resistin adipokines have been described as po

49 Upon STAT3 silencing, leptin and resistin lost their ability to activate PCSK9

50 wn of STAT3 did not affect the expression of leptin and resistin receptors or that of PCSK9.

51 ensity lipoprotein metabolism, is induced by leptin and resistin through the involvement of the infla

52 In HepG2 cells, leptin and resistin up-regulated PCSK9 gene and protein

53 ilitated primarily by adipose tissue-derived leptin and SNS-derived noradrenaline.

54 Leptin and soluble leptin receptor were two hubs of the

55 ad 2.8-ng/mL (95% CI: 0.3, 5.3 ng/mL) higher leptin and tended to have lower fasting glucose (-0.8 mm

56 vely correlated with fasting glucose, plasma leptin, and apolipoprotein C3 (APOC3) concentrations.

57 ) (-/-) mice normalized circulating insulin, leptin, and epidermal growth factor levels.

58 d amplitude of melatonin, cortisol, ghrelin, leptin, and glucose were not differentially altered by t

59 ncreased G-CSF, GM-CSF, IL-13, IL-6, IL-17a, leptin, and IL-4 that discriminated between stress conte

60 1), NF-kappaB, and the inflammatory cytokine leptin, and incurred loss of the pro-apoptotic protein C

61 exposed to higher concentrations of insulin, leptin, and, to a lesser extent, CRP.

62 STAT3 as one of the molecular regulators of leptin- and resistin-mediated transcriptional induction

63 Cholecystokinin (CCK) and leptin are satiety-controlling peptides, yet their inter

64 Insulin and leptin are two sympathoexcitatory hormones that increase

65 leptin tolerance and questioning the role of leptin as regulator of energy balance in humans.

66 expression of the adipokines adiponectin or leptin, associated with distinct transcription factors p

67 Here, we report that leptin augments NMDAR function via Src kinase-mediated p

68 abolished detectable induction of the nearby leptin b gene during regeneration, deletions of enhancer

69 diet-induced obesity (DIO) are resistant to leptin because of poor permeability of the blood-brain b

70 or (sOb-R), secreted by the liver, regulates leptin bioavailability and bioactivity.

71 eating severity also directly correlated to leptin, body weight and adiposity.

72 e diabetic human donors failed to respond to leptin but hyperpolarized in response to NMDA.

73 We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in in

74 In mice with DIO, intranasal leptin bypassed leptin resistance and significantly atte

75 cross-linking effect of glutaraldehyde, anti-leptin can be firmly fixed.

76 FFA induce leptin receptors, whereas higher leptin causes migration.

77 ased body weight gain, circulating levels of leptin, cholesterol, HDL and LDL in C57BL/6J whereas WSB

78 Median (IQR) leptin concentration was 15.2 ng/mL (10.2-17.3 ng/mL) in

79 Here we show that refeeding increases plasma leptin concentrations approximately 8-fold in 48-hour-fa

80 Leptin concentrations are strongly related to adiposity,

81 Whether inheritance of leptin concentrations is quantile dependent, and whether

82 lean rats, and this normalization of plasma leptin concentrations stimulates adrenomedullary catecho

83 ncestry only, and its association with lower leptin concentrations was specific to this ancestry (P =

84 genetic and shared environmental effects on leptin concentrations were quantile dependent, which lik

85 c variants that influence adiposity-adjusted leptin concentrations.

86 tent with quantile-dependent expressivity of leptin concentrations.

87 sibs, which was attributable to their higher leptin concentrations.

88 y both contribute to short-term satiety, and leptin could positively modulate CCK signalling.

89 on, with higher insulin, insulin resistance, leptin, CRP, IL-1RA, and IL-6, and lower ghrelin than su

90 Leptin decreased MTP expression in differentiated intest

91 are LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that

92 In summary, leptin deficiency did not attenuate HU-induced osteopeni

93 in vitro induction of ER stress and neonatal leptin deficiency in vivo activate hypothalamic autophag

94 atment of individuals with lipodystrophy and leptin deficiency is well established.

95 we visualized projections of PPG neurons in leptin-deficient Lep(ob/ob) mice and found that projecti

96 Here, we show that leptin-deficient ob/ob mice display elevated hypothalami

97 les of the offspring's age- and sex-adjusted leptin distribution (P(linear) = 0.0001), which was acce

98 eptin levels before treatment initiation and leptin dose do not predict the observed weight loss in l

99 However, the actual role of leptin during development is not yet fully understood.

100 m our clinical trials biobank to investigate leptin effects on mechanisms of weight regulation in lea

101 These leptin effects required the presence of leptin receptors

102 We found that leptin enhanced carotid sinus nerve activity at baseline

103 In PVN slices from mice expressing GCaMP6, leptin excites glutamatergic neurons.

104 we report that fat-specific and quantitative leptin expression is controlled by redundant cis element

105 erferon-gamma expression and induced adipose leptin expression via increased miR181b-5p and miR219-5p

106 The successful use of leptin for the treatment of individuals with lipodystrop

107 ructure prediction confirms that in solution leptin forms a four-helix bundle including a pierced las

108 Lipid, leptin, free fatty acids, and inflammatory marker levels

109 isceral adipose tissue area (cm(2)), lipids, leptin, free fatty acids, inflammatory markers, and acti

110 Mutations in the leptin gene (ob) result in a metabolic disorder that inc

111 hat iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cA

112 -binding protein (pCREB) at two sites in the leptin gene promoter.

113 d medullary centers, whereas intraperitoneal leptin had no effect.

114 L15, IP10, TNFalpha, and decreased levels of leptin, heparin cofactor 2, and serum paraoxonase were a

115 Leptin, however, elicited migration of macrophages from

116 The leptin immunosensor displayed excellent selectivity and

117 To uncover the importance of leptin in early life, the present study restored leptin

118 ich negatively regulates adiponectin but not leptin in mice fed chow diet.

119 However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood.

120 determined that males have higher levels of leptin in serum and adipose tissue.

121 ed mediation analysis to examine the role of leptin in the associations of early-life nutrition and a

122 ells, including the intrinsic involvement of leptin in the control of mucosal homeostasis.

123 We aimed to investigate the role of leptin in the differential association between early-lif

124 higher concentrations of the satiety hormone leptin in the morning (P = 0.001).

125 Leptin increased nuclear immunoreactivity against phosph

126 gh-frequency stimulation of vagal afferents, leptin increased the size of NMDAR-mediated currents, bu

127 We found that leptin increases phosphorylation of Tyr-418 in Src, an i

128 We found that leptin increases the sensitivity of LepR-expressing neur

129 The adipocyte-derived hormone leptin increases trafficking of K(ATP) and Kv2.1 channel

130 ance toward a lean phenotype via a primarily leptin-independent mechanism.

131 Free leptin index (FLI) was calculated as the ratio of leptin

132 for leptin receptor concentrations and free leptin index also increased significantly with increasin

133 Intranasal leptin induced signal transducer and activator of transc

134 In the rat ventromedial hypothalamus (VMH), leptin-induced action potential firing was enhanced, whe

135 pression, which in turn is indispensable for leptin-induced antidepressant-like effects.

136 s of function human variant (SRC-1(L1376P)), leptin-induced depolarization of Pomc neurons and Pomc e

137 Leptin-induced membrane hyperpolarization diminished upo

138 ylated STAT3 (pSTAT3) whereas CCK-8s reduced leptin-induced nuclear pSTAT3 accumulation in these cell

139 and that NTS NMDAR activation contributes to leptin-induced reduction of food intake.

140 yet, pregnancy impairs central insulin- and leptin-induced signalling.

141 Mechanistically, we show that leptin induction activates the mTORC2/Akt pathway and su

142 Leptin influences food intake by informing the brain abo

143 Leptin informs the brain about sufficiency of fuel store

144 At the molecular level, we found that leptin inhibited the expression of forkhead-boxP3 (FoxP3

145 os (a marker of amylin activation); Socs3 (a leptin inhibitor); and Cart, Pomc and Npy (neuropeptides

146 of overnight food intake following intra-NTS leptin injection.

147 effects of acute G(q) signaling and also of leptin insensitivity.

148 y-regulating neuroendocrine signaling (e.g., leptin, insulin).

149 Leptin, insulin, and C-reactive protein (CRP) were measu

150 Human milk leptin, insulin, and CRP concentrations were higher in O

151 Further experiments also suggested that leptin interacted with long-form LEPR (ObRb), highly exp

152 In contrast, in the liver, leptin interacted with short-form LEPR (ObRa) to increas

153 Injection of leptin into the NTS inhibits food intake, while knockdow

154 he control of food intake, and injections of leptin into the NTS reduce meal size and increase the ef

155 ivity to vagal inputs.SIGNIFICANCE STATEMENT Leptin is a hormone that critically impacts food intake

156 Leptin is an adipocyte-derived hormone with pleiotropic

157 Leptin is an important signaling hormone, mostly known f

158 We have previously shown that this effect of leptin is mediated by the NMDA subtype of glutamate rece

159 determined on several timescales, show that leptin is monomeric, has a rigid four-helix scaffold, an

160 ced osteopenia in male mice, suggesting that leptin is not required for bone loss induced by unweight

161 Our results indicate that leptin is required for human immune homeostasis and cont

162 nt depends upon whether the phenotype (e.g., leptin) is high or low relative to its distribution.

163 e; increases in propionate with increases in leptin, LDL cholesterol, and blood pressure; and increas

164 o displayed a decrease in plasma insulin and leptin levels and an increase in amylin and GLP-1 levels

165 show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, wh

166 Leptin levels before treatment initiation and leptin dos

167 d leptin levels, whereas only associate with leptin levels in obese OSA patients.

168 ls a model in which a reduction of bioactive leptin levels in the context of obesity triggers a high

169 The increased leptin levels induced by glucosamine were susceptible to

170 Among women age <51 years, high leptin levels were significantly associated with decreas

171 ng HFD-treated male mice had increased serum leptin levels, and serum exosomal miR181b-5p and miR219-

172 beta1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels

173 cells is attenuated in the presence of high leptin levels.

174 t males showed the highest G-CSF, IL-13, and leptin levels.

175 omes important in obesity, in which elevated leptin maintains the hypothalamic pituitary thyroid axis

176 he sympathoexcitatory effects of insulin and leptin may contribute to elevated basal SNA, and therefo

177 Leptin mediated 34.9% of the pathway between early-life

178 Leptin mediated the glucose-lowering effect of early-lif

179 Our results also indicated that leptin-mediated MTP regulation in the intestine affects

180 1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst

181 en well characterized, and it is unclear how leptin might act on these neurons to reduce food intake.

182 ur study reveals a signaling pathway wherein leptin modulates NMDARs via Src to regulate beta-cell ex

183 n and fat mass, and increased adipose tissue leptin mRNA expression in HFD-treated recipient mice.

184 animals with marked resistance to diet- and leptin-mutation-induced obesity.

185 The effects of leptin on innervation are mediated via agouti-related pe

186 Deletion of BDNF(PVH) blunts the effects of leptin on innervation.

187 However, the effect of leptin on minute ventilation (V(E) ) and the hypoxic ven

188 s, here we sought to identify the effects of leptin on MTP expression in the intestine and liver.

189 the effects of the adipose-secreted hormone, leptin, on insulin sensitivity.

190 n treatment increases, whereas deficiency of leptin or leptin receptors decreases, total Bdnf mRNA le

191 f age, sex, body mass accrual and functional leptin or melanocortin-4 receptor signaling.

192 for ACTH (increased in GG only) and insulin, leptin, osteocalcin (decreased in NGG only) at day 6 (P

193 Furthermore, leptin plays a major role in other proteinopathies, such

194 Leptin positively correlates with adiposity and has gluc

195 However, the molecular mechanism by which leptin potentiates NMDARs in beta-cells remains unknown.

196 In rat C6 glioma cells, leptin pre-treatment enhanced Ca(2+) mobilization by a C

197 Mechanistically, exercise diminishes leptin production in adipose tissue, augmenting quiescen

198 ulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.

199 hat Egr1 directly binds to and activates the leptin promoter.

200 th week of age in mice formerly null for the leptin receptor (LepR) gene.

201 Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component o

202 ying ablation of GH receptor (GHR) either in leptin receptor (LepR)- or steroidogenic factor-1 (SF1)-

203 Here, we show that the leptin receptor (LepRb) colocalizes with brain-derived n

204 The soluble isoform of leptin receptor (sOb-R), secreted by the liver, regulate

205 Leptin receptor and free fatty acid (FFA) receptor, GPR1

206 beta(FS) for leptin receptor concentrations and free leptin index als

207 Therefore, leptin and leptin receptor concentrations from 3068 siblings in 113

208 calculated as the ratio of leptin to soluble leptin receptor concentrations.

209 ease in Wnt2b expression under conditions of leptin receptor deficiency, which also induced a delay i

210 Deletion of the gene encoding the leptin receptor in either population leads to reduced in

211 Leptin and soluble leptin receptor were two hubs of the network, with large

212 A long functional isoform of leptin receptor, LepR(b) , was detected in the carotid b

213 We crossed diabetic leptin receptor-mutant mice to mice lacking CaMKIIdelta

214 ditional deletion of Vegfc in endothelial or leptin receptor-positive (LepR+) cells led to a disrupti

215 Leptin receptor-positive cells were synaptically connect

216 ndent db/db mice harboring a mutation in the leptin receptor.

217 nce-promoting hematopoietic niche factors in leptin-receptor-positive stromal bone marrow cells.

218 mobilize Ca(2+) even in cells overexpressing leptin receptors (C6-ObRb).

219 h inducible endothelium-specific deletion of leptin receptors (End.LepR-KO) or littermate controls (E

220 c nerve activity (SNA) is unclear, since PVN leptin receptors (LepR) are sparse.

221 Leptin receptors (LepRs) are expressed by vagal afferent

222 NTS inhibits food intake, while knockdown of leptin receptors (LepRs) in NTS neurons increases food i

223 hese leptin effects required the presence of leptin receptors (LEPRs).

224 ers were used to examine connections between leptin receptors and respiratory motoneurons.

225 t increases, whereas deficiency of leptin or leptin receptors decreases, total Bdnf mRNA levels, with

226 ctions were normalized by targeted rescue of leptin receptors in LepRb(TB/TB) mice, which lack functi

227 preproglucagon (PPG) neurons, which express leptin receptors in the mouse and send direct projection

228 pe 2 diabetes mouse model lacking functional leptin receptors, or from obese diabetic human donors fa

229 cific migration because increased FFA induce leptin receptors, whereas higher leptin causes migration

230 (TB/TB) mice, which lack functional neuronal leptin receptors.

231 ptional regulation for long-term satiety via leptin receptors.

232 ceptual steps that led us to explore partial leptin reduction as a viable therapeutic avenue.

233 to potential future applications of partial leptin reduction therapy for the treatment of obesity an

234 children but not in adults, suggesting that leptin regulates early adiposity.

235 The hormone leptin regulates fat storage and metabolism by signaling

236 In summary, our findings suggest that leptin regulates MTP expression differentially by engagi

237 t another way, hyperleptinemia per se causes leptin resistance and associated metabolic disorders.

238 em is involved in the development of hepatic leptin resistance and in the regulation of sOb-R levels

239 In mice with DIO, intranasal leptin bypassed leptin resistance and significantly attenuated sleep-dis

240 emerged as a critical mechanism involved in leptin resistance and type 2 diabetes in adult individua

241 and neurodevelopmental deficits and reversed leptin resistance in the offspring of obese dams.

242 or a better understanding of the much famed "leptin resistance" phenomenon.

243 sity (DIO) contribute to hyperleptinemia and leptin resistance, effects that are regulated by the end

244 m exposure-PM(2.5) is even worse, leading to leptin resistance, hyperphagia, and decreased EE.

245 n-1's actions are preserved in conditions of leptin resistance, the present findings render the NUCB2

246 sts NMDARs as a potential target to overcome leptin resistance.

247 associated with neonatal hyperleptinemia and leptin resistance.

248 he maternal lipidome, and prevented maternal leptin resistance.

249 ic CB(1)R modulates sOb-R levels and hepatic leptin resistance.

250 hypothalamic pituitary thyroid axis, despite leptin resistance.

251 high dietary fat consumption, likely due to leptin resistance; however, the behavioral and metabolic

252 Here we report that ob/ob mice, as well as leptin-resistant diet-induced obese mice, show significa

253 cytokine secretions, such as adiponectin and leptin, resulting in a decrease in anti-oxidative respon

254 on of AgRP neurons in diabetic mice reversed leptin's ability to inhibit feeding but did not counter

255 ility to inhibit feeding but did not counter leptin's ability to lower blood glucose levels.

256 While leptin's role in the regulation of appetite has been ext

257 ses, we show that the Met94 allele decreases leptin secretion.

258 With regard to hunger, it is thought that leptin-sensing neurons work entirely via circuits within

259 mmune-derived miRNAs and cytokine, activates leptin sensitivity and expression that subsequently inhi

260 However, alphadeltaKO mice exhibit leptin sensitivity that is similar to that of wild-type

261 Elafin improved leptin sensitivity via reduced interferon-gamma expressi

262 sing candidate to treat obesity by improving leptin sensitivity.

263 of its promoter, while CHOP deletion reduced leptin sensitivity.

264 context of obesity triggers a high degree of leptin sensitization and improved leptin action, both ce

265 ely resistant to the effects of celastrol in leptin sensitization and treatment of obesity, diabetes,

266 The mechanism of celastrol's leptin-sensitizing and antiobesity effects has not yet b

267 d 24-h average levels of the satiety hormone leptin sex-dependently (P < 0.0001), with a ~7% decrease

268 in in early life, the present study restored leptin signaling either at the fourth or tenth week of a

269 To examine the importance of endothelial leptin signaling in cardiac hypertrophy, transverse aort

270 Leptin signaling within the nucleus of the solitary trac

271 ity's established, and the long term affects leptin signaling/action due to inflammation.

272 These data show that leptin signalling regulates the plasticity of sympatheti

273 ivating CNS neurons, albeit independently of leptin, similarly recruits and requires this pathway by

274 We show in rats that PVN leptin slowly increases SNA to muscle and brown adipose

275 neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impai

276 In summary, these data demonstrate that leptin stimulates a hypothalamus-adrenal medulla-BAT axi

277 Leptin stimulates the sympathetic nervous system (SNS),

278 Meanwhile, leptin stimulation alone failed to mobilize Ca(2+) even

279 In line with these results, leptin stimulation significantly increased the prolifera

280 thalamic response to the circulating hormone leptin, suggesting a novel way to regulate brain entry t

281 Notably, maternal nutrition and postnatal leptin surge have a profound impact on ciliogenesis in t

282 However, pharmacological approaches of leptin therapy for the treatment of diet-induced obesity

283 Estrogens act with leptin to regulate energy homeostasis in females.

284 n index (FLI) was calculated as the ratio of leptin to soluble leptin receptor concentrations.

285 ophobic core, pinning down the long loops of leptin to the protein body, inducing motional restrictio

286 leptin treatment, suggesting the presence of leptin tolerance and questioning the role of leptin as r

287 In contrast to data from animal studies, leptin treatment does not affect energy expenditure, lip

288 Leptin treatment increases, whereas deficiency of leptin

289 Similarly, acute and chronic leptin treatment of chow diet-fed WT mice decreased MTP

290 Chronic leptin treatment of ob/ob mice restores adipose tissue s

291 g refeeding after fasting, whereas long-term leptin treatment reduces fat mass and body weight, and t

292 se are hyperleptinemic and do not respond to leptin treatment, suggesting the presence of leptin tole

293 d plasma leptin levels and lose weight after leptin treatment, whereas control mice do not.

294 creased abundance of the S24-7 family, while leptin was associated with increases in Coriobacteriacea

295 Based on studies in mice, leptin was expected to decrease body weight in obese ind

296 Leptin was positively correlated with BMI (Spearman's rh

297 sympathoexcitatory responses to insulin and leptin were abolished in pregnant rats.

298 These effects of leptin were blocked by bath applying a competitive NMDAR

299 howed that receptors of the hormone/cytokine leptin were highly expressed, and we found a decrease in

300 nase-dead Src mutant prevented the effect of leptin, whereas a Src kinase activator peptide mimicked