ライフサイエンスコーパス: apelin

1 equence similarity to the established ligand apelin.

2 ed phenotypes, associated with expression of apelin.

3 tion of EC targets of BMP signaling, such as apelin.

4 assessed under IV osmotic pump infusions of apelin-13 (0.25 mug/kg/min) or dobutamine (7.5 mug/kg/mi

5 [Pyr(1)]apelin-13 (135 nmol/min) was infused into six healthy hu

6 (Pyr(1))-apelin-13 (2 mg/kg/day) or saline was infused in TGA-PE

7 infusions of the apelinergic agonists ELA or Apelin-13 (39 and 15 microg/kg/hr, respectively) versus

8 he improved method, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major apelin isoform p

9 We show that [Pyr(1) ]apelin-13 acts as a modulating neurotransmitter in the n

10 stablished the systemic outcomes of (Pyr(1))-apelin-13 administration in rats with preeclamptic featu

11 Although apelin-13 and ELA both target APJ, there is limited info

12 tection and quantification of intact [Pyr(1)]apelin-13 and have used this method to identify the meta

13 method for quantification of intact [Pyr(1)]apelin-13 and its metabolites in human plasma.

14 s2235312T were associated with low levels of apelin-13 and nitrite (P < 0.05).

15 Apelin-13 and nitrite levels and apelin and NOS3 express

16 However, ELA proved better than Apelin-13 by improving fluid homeostasis, cardiovascular

17 del and in both in vivo and ex vivo studies, apelin-13 compared with dobutamine provoked distinctive

18 (Pyr(1))-apelin-13 did not affect maternal or fetal weights in TG

19 , consistent with the hemodynamic profile of apelin-13 in an acute pressure volume loop model.

20 suggest that the pressor action of [Pyr(1) ]apelin-13 in the RVLM of normotensive rats is not mediat

21 (Pyr(1))-apelin-13 increased ejection fraction in TGA-PE rats.

22 By contrast, the [Pyr(1) ]apelin-13 induced pressor and sympathoexcitatory effects

23 ions of APJ agonism during prolonged (Pyr(1))apelin-13 infusion and renin-angiotensin system activati

24 Prolonged 6-hour (Pyr(1))apelin-13 infusion caused a sustained increase in cardia

25 his inflammatory cardiovascular dysfunction, apelin-13 infusion delivers distinct and optimized hemod

26 f the apelinergic system by exogenous ELA or Apelin-13 infusion improves cardiovascular function and

27 Systemic intravenous (Pyr(1))apelin-13 infusion increased cardiac index, whereas redu

28 or prolonged systemic (30 nmol/min) (Pyr(1))apelin-13 infusions in the presence or absence of renin-

29 Bilateral microinjection of [Pyr(1) ]apelin-13 into the rostral ventrolateral medulla (RVLM),

30 Apelin-13 is a powerful inotropic candidate that could b

31 [Pyr(1)]apelin-13 is the predominant apelin peptide isoform in t

32 ed luminal secretion of the pyroglutaminated apelin-13 isoform ([Pyr-1]-apelin-13) in the small intes

33 ociated with decreased apelin expression and apelin-13 levels.

34 al29, Pro30, Phe31, Pro32) show that ELA and apelin-13 may interact differently with APJ.

35 date, few studies have investigated [Pyr(1)]apelin-13 metabolism in vivo in rats with no studies exa

36 (Pyr(1))-apelin-13 normalized proteinuria in association with low

37 dult males) to assess the effects of ELA and Apelin-13 on vascular and cardio-renal function.

38 Using the mutant form of the natural apelin-13 peptide, the authors showed reduction of both

39 The administration of (Pyr(1))-apelin-13 reduced blood pressure, and normalized heart r

40 Since Apelin-13 signals through its receptor (Apelin peptide j

41 Bilateral RVLM microinjection of [Pyr(1) ]apelin-13 significantly increased ABP (9 +/- 1 mmHg) com

42 d for the first time that in humans, [Pyr(1)]apelin-13 was cleaved from both termini but the C-termin

43 Apelin-13 was recently proposed as an alternative to the

44 Acute cardiac effects of ELA-32 and [Pyr(1)]apelin-13 were assessed by MRI and cardiac catheterizati

45 entified, [Pyr(1)]apelin-13((1-12)), [Pyr(1)]apelin-13((1-10)) and [Pyr(1)]apelin-13((1-6)) were the

46 ntly, of the metabolites identified, [Pyr(1)]apelin-13((1-12)), [Pyr(1)]apelin-13((1-10)) and [Pyr(1)

47 -12)), [Pyr(1)]apelin-13((1-10)) and [Pyr(1)]apelin-13((1-6)) were the most abundant.

48 pyroglutaminated apelin-13 isoform ([Pyr-1]-apelin-13) in the small intestine of mice.

49 se beneficial renal effects were superior to Apelin-13, likely because full-length ELA enabled a dist

50 demonstrated comparable in vitro potency to apelin-13, the endogenous peptidic ligand for the APJ re

51 ssion was also reduced with the treatment of apelin-13, which deacetylates histones.

52 Our study identified new potent analogues of apelin-13, which represent valuable probes to better und

53 y can robustly measure endogenous Ang II and apelin-13-converting activities involved in the renin-an

54 In vitro studies confirmed that these apelin-13-driven processes encompassed a significant and

55 erine residues had no demonstrable impact on apelin-13-induced G protein activation and its intracell

56 e vasopressin V1a receptor but that [Pyr(1) ]apelin-13-induced sympathoexcitation is independent of a

57 etion and angiotensin II coinfusion, (Pyr(1))apelin-13-induced vasodilatation was preserved (P<0.02 f

58 nisms involved in the regulation of [Pyr(1) ]apelin-13-mediated cardiovascular control within the ros

59 The [Pyr(1) ]apelin-13-mediated pressor response and the increased lo

60 ncy to inhibit cAMP accumulation compared to apelin-13.

61 sustained drop in blood pressure compared to apelin-13.

62 ore potent to inhibit cAMP accumulation than apelin-13.

63 beta-arrestin recruitment to APJ induced by apelin-13.

64 lso suitable for measuring the conversion of apelin-13.

65 od, we detected pyroglutamyl apelin-13 [(pyr)apelin-13] as the major apelin isoform present in plasma

66 previously showed that the C-terminal Phe of apelin 17 (K17F) is crucial for triggering apelin recept

67 Apelin-17 has especially potent cardio-physiological eff

68 use plasma (T1/2 > 10 h) than the endogenous apelin-17 peptide 2 (T1/2 < 4 min).

69 An alanine scan of apelin-17 reveals that the integrity and conformational

70 (30kDa-PEG)] is 10,000-fold less potent than apelin-36 at activating the APJ receptor but retains its

71 e demonstrate that the metabolic activity of apelin-36 can be separated from canonical APJ activation

72 Apelin-36 has been linked to two major types of biologic

73 ndings to develop a longer-acting variant of apelin-36 that could modulate glucose homeostasis withou

74 We developed a series of apelin-36 variants in which evolutionarily conserved res

75 Apelin-36 was discovered as the endogenous ligand for th

76 In contrast to its full metabolic activity, apelin-36(L28A) lost the ability to suppress blood press

77 We found that apelin-36(L28A) retains full metabolic activity, but is

78 Apelin-36-[L28C(30kDa-PEG)] is 10,000-fold less potent t

79 Apelin-36-[L28C(30kDa-PEG)] provides a starting point fo

80 improved endothelial function by increasing apelin, a BMPR2 target.

81 roblast transition by functionally targeting apelin, a critical repressor of fibrogenesis.

82 nducible factor stimulates the expression of apelin, a potent vasodilator, in response to reduced blo

83 ystem, adding a conceptual framework for the apelin-ACE2-angiotensin 1-7 axis as a therapeutic target

84 Thus, apelin acted as an autocrine growth cue to sustain vascu

85 eta-arrestins or by pharmacological doses of apelin acting through Galphai.

86 Apelin activity was associated with phosphorylation of A

87 transport of glucose, and 4) intraperitoneal apelin administration in neonates increased glucose upta

88 IV apelin administration induced excessive bleeding and pre

89 enal injury without fetal toxicity following apelin administration suggesting a role for apelin in th

90 r levels of the 2 potent vasodilator factors apelin and ADM (adrenomedullin) compared with Bmp9(+/+)

91 The apelin and apelin receptor (APJ) system is involved in t

92 Apelin and APLNR are broadly expressed in human GBM, and

93 reased expression of the EC tip cell markers apelin and Dll4 and is associated with a reduction in mi

94 (2015) demonstrate that the secreted protein Apelin and hematopoietic-endothelial cell interactions c

95 sequently, human and mouse platelets express apelin and its receptor APJ.

96 Apelin and its receptor are widely distributed in the br

97 Growing evidences indicate that apelin and its receptor, APJ, which are expressed across

98 Apelin-13 and nitrite levels and apelin and NOS3 expression were down-regulated in HAPE-p

99 the brown adipogenic and browning effects of apelin and suggests a potential therapeutic route to com

100 Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful a

101 tion and induced target genes, such as APLN (apelin) and JAG1, to regenerate pulmonary microvessels a

102 tide), hormonal (e.g., gastrin, ghrelin, and apelin), and paracrine (e.g., histamine) pathways as wel

103 can affect the balance between endothelin-1, apelin, and adrenomedullin.

104 ion of the potent angiogenic factors VEGF-A, apelin, and angiopoietin-like protein 4.

105 tip cells, such as angiopoietin-2, ESM1, and Apelin, and impaired tip cell formation.

106 ibits a cardiovascular profile comparable to apelin, and is downregulated in human disease and rodent

107 rgeting of apelin cognate receptor abrogates apelin- and endothelial-mediated expansion of glioblasto

108 FA protein and mRNA for delta-like ligand 4, apelin, angiopoietin-2, and monocyte chemoattractant pro

109 ate the genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric

110 The apelin-apelin receptor system affects arterial blood pre

111 ls novel HPA-responsive pathways such as the Apelin-Apelin receptor system.

112 Therefore, the apelin/apelin receptor signalling nexus may operate as a

113 noncanonical signaling pathway downstream of apelin-APJ involving Galpha13, which induces histone dea

114 Our results demonstrate a novel role for apelin-APJ signaling as a potent regulator of endothelia

115 Here, we report that apelin-APJ signaling promotes brown adipocyte differenti

116 ommonly shared transcriptional targets among apelin-APJ, Galpha13, and MEF2 in endothelial cells, whi

117 croRNA (miRNA)-dependent association between apelin (APLN) and fibroblast growth factor 2 (FGF2) sign

118 These included the genes for apelin (Apln) and for its receptor (Aplnr), both of whic

119 (GPCR) signalling, including that involving apelin (APLN) and its receptor APLNR, is known to be imp

120 We investigated the direct role of apelin (APLN) in AAA and identified a unique approach to

121 During embryonic development, Apelin (APLN) is robustly expressed in vascular ECs.

122 As neither of the ligands Ela or Apelin (Apln) nor their receptors have previously been i

123 that expression of the proangiogenic peptide apelin (APLN) was decreased and GBM cell invasion was in

124 nding of the fluoresceinated peptide ligand, APELIN (APLN), or an anti-APLNR mAb, were found in both

125 study and sequencing identified variants of apelin, APLNR, and NOS3 that were validated in a larger

126 A central role for apelin/APLNR in controlling GBM vascularization was corr

127 In summary, we show that apelin/APLNR signaling controls GBM angiogenesis and inv

128 y, both oxidative stress and plasma level of apelin are increased.

129 the identification of the vasoactive peptide apelin as a central regulator for endothelial-mediated m

130 r, these initial data identify proangiogenic apelin as a key mediator of coronary vascular repair and

131 Our data support the promises of apelin as a novel strategy to improve MSC-based therapy

132 blood pressure (BP) but is not required for apelin binding or Gi protein coupling.

133 Conversely, pharmacologic apelin blockade in the intestine reduced the increased g

134 Genetic and pharmacological targeting of apelin cognate receptor abrogates apelin- and endothelia

135 Apelin concentrations have historically been measured by

136 measured by immunoassays; however, reported apelin concentrations measured in healthy volunteers sho

137 Together, our data demonstrate that apelin controls fetal and neonatal glucose homeostasis a

138 Methylation of the apelin CpG island was significantly higher in HAPE-p at

139 The glucose-apelin cycle might be pharmacologically handled to regul

140 Here we found that ACE2 was downregulated in apelin-deficient mice.

141 s to be realized due to rapid proteolysis of apelin-derived peptides by proteases, including neprilys

142 Apelin directly interferes with thrombin-mediated signal

143 Mice lacking apelin displayed a shorter bleeding time and a prothromb

144 and in vivo, protamine abolishes well-known apelin effects, such as angiogenesis, glucose tolerance,

145 Comparable to apelin, ELA increased cardiac contractility, ejection fr

146 energy balance signals such as adiponectin, apelin, endocannabinoids, leptin, insulin and peptide YY

147 Apelin exists in several isoforms ranging in size from 1

148 the 5' UTR and was associated with decreased apelin expression and apelin-13 levels.

149 Moreover, APELIN expression is regulated by Notch signaling in hum

150 However, reduction in apelin expression led to accelerated GBM cell invasion.

151 In line with this finding, apelin expression was upregulated in the infarcted myoca

152 gged1, Dll4, Hey1, Hey2, Hes1) and decreased apelin expression, suggesting a possible cross-talk betw

153 We suggest that apelin-F13A can improve the efficiency and reduce the si

154 Application of apelin-F13A, a mutant APLNR ligand, blocked tumor angiog

155 that both pathologic features are blunted by apelin-F13A.

156 Our findings indicated that apelin facilitated AD-MSCs-based therapy in PAD, possibl

157 In vivo, loss of donor heart expression of apelin facilitated graft immune cell infiltration, blunt

158 For this purpose, we have used apelin fragments K17F and K16P (K17F with the C-terminal

159 We conclude that apelin functions as a new and potent chemoattractant for

160 mined in jejunal loops and in mice following apelin gavage.

161 ntagonistic relationship between the RAS and apelin has been proposed, such functional interplay rema

162 Apelin has been shown to protect bone marrow MSCs agains

163 These findings suggest that in these models apelin has minimal effect on sprouting retinal angiogene

164 receptor and its endogenous peptidic ligand apelin have been implicated as important modulators of c

165 ity (Apom, Pgc1alpha) and immune modulation (Apelin, Icam1) compared to WT mice.

166 iphasic response in autophagy was induced by apelin in AD-MSCs during hypoxia and hypoxia/reoxygenati

167 time, reveals the antioxidant properties of apelin in adipocytes, and suggests its potential as a no

168 iated vasculopathy upregulated expression of apelin in arteries and myocardial microvessels.

169 We confirmed a new pro-inflammatory role of Apelin in AS mice and in cultured human GEC.

170 activity of this system in rats, the role of apelin in fetal and neonatal glucose homeostasis, and it

171 f the CpG island influence the expression of apelin in HAPE.

172 ELA competed for binding of apelin in human heart with overlap for the 2 peptides in

173 vivo, the placenta released high amounts of apelin in late gestation, 3) intravenous apelin injectio

174 apelin administration suggesting a role for apelin in the regulation of maternal outcomes in preecla

175 apelin receptor APLNR and its cognate ligand apelin in VEGFA/VEGFR2 antiangiogenic therapy against di

176 Apelin increased specific glucose flux through the gastr

177 Mechanistically, apelin increased the viability of AD-MSCs via promoting

178 In addition, apelin increases the basal activity of brown adipocytes,

179 APJ ligand) remain sensitive, suggesting an apelin-independent function of APJ.

180 ese and insulin-resistant mice treated by an apelin injection (0.1 mumol/kg/day i.p.) during 4 weeks

181 of apelin in late gestation, 3) intravenous apelin injection in mothers increased the transplacental

182 Injection of apelin into the ischemic myocardium resulted in accelera

183 l expansion and progression, suggesting that apelin is a druggable factor in glioblastoma.

184 Here, we show that apelin is a key player in hemostasis with an ability to

185 Apelin is a peptide that regulates glucose homeostasis a

186 Apelin is a second catalytic substrate for ACE2 and func

187 ABSTRACT: Apelin is a ubiquitous peptide that can elevate arterial

188 vide both in vitro and in vivo evidence that apelin is able to increase the brown-like characteristic

189 We further demonstrate that apelin is able to relieve oxidative stress-induced dysre

190 Apelin is an adipocyte-derived hormone that plays import

191 Apelin is an adipocytokine secreted by adipocytes, and k

192 Apelin is an important contributor to the renin-angioten

193 Apelin is an important mammalian peptide hormone with a

194 Apelin is emerging as an important hormone regulator of

195 Apelin is the endogenous ligand for the previously orpha

196 Apelin is the endogenous ligand of the APJ receptor, a m

197 amyl apelin-13 [(pyr)apelin-13] as the major apelin isoform present in plasma from several healthy vo

198 escued hypertrophy and heart dysfunctions of apelin-knockout mice.

199 In proneural GBM, apelin levels were downregulated by VEGFA or VEGFR2 bloc

200 emination of APLNR-positive tumor cells when apelin levels were reduced.

201 ; however, the central mechanisms underlying apelin-mediated changes in sympathetic nerve activity an

202 In endothelial cells, miR-130/301 modulated apelin-miR-424/503-FGF2 signaling, while in smooth muscl

203 he impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored AC

204 The effects of apelin on (14)C-labeled glucose transport were determine

205 However, the effects of apelin on fatty acid oxidation (FAO) during obesity-rela

206 secretion by enterocytes and the effects of apelin on intestinal glucose absorption.

207 The net effect of apelin on intestinal glucose transepithelial transport w

208 However, the regulatory roles of apelin on oxidative stress in adipocytes remain unknown.

209 Apelin peptide and its receptor APJ are directly implica

210 [Pyr(1)]apelin-13 is the predominant apelin peptide isoform in the human cardiovascular syste

211 ELA (ELA), a second endogenous ligand of the Apelin peptide jejunum receptor highly expressed in the

212 ince Apelin-13 signals through its receptor (Apelin peptide jejunum) to exert singular inotropic/vaso

213 Our data confirm a role for the apelin peptide system in cardiovascular regulation at th

214 the inherent rapid degradation of endogenous apelin peptides and produce metabolically stable small m

215 tivity relationships for chemically modified apelin peptides and recent disclosures of small molecule

216 Apelin peptides and the apelin receptor represent a rela

217 Apelin peptides are labile in plasma at physiological co

218 wering the plasma pH to 4.5, the recovery of apelin peptides can be increased significantly.

219 These data suggest that apelin peptides designed for use as cardiovascular thera

220 the lower limit of detection for most of the apelin peptides monitored to a few pg/ml.

221 orts suggest apelin receptor activation with apelin peptides results in cardioprotection as noted thr

222 his study, an optimized method for enriching apelin peptides with cation-exchange beads followed with

223 sis underlying the functional selectivity of apelin peptides, our study indicates that the beta-arres

224 n receptor (Aplnr) and its endogenous ligand apelin play an important role in cardiovascular developm

225 Apelin plays a prominent role in body fluid and cardiova

226 f neurotransmitter systems through which the apelin pressor response may occur within the RVLM.

227 Here we demonstrated that apelin promoted functional survival of AD-MSCs in ischem

228 s further supported by the observations that apelin promotes the expression of anti-oxidant enzymes v

229 The apelin receptor (APJ) belongs to family A of the G prote

230 The apelin and apelin receptor (APJ) system is involved in the regulati

231 scovered as a novel endogenous ligand of the apelin receptor (APJ), a G protein-coupled receptor.

232 ce that apelin, through its interaction with apelin receptor (APJ), suppresses production and release

233 (ELA) is the second endogenous ligand of the apelin receptor (APJ).

234 hich highlights the importance of inhibiting apelin receptor (APJ); therefore, we developed a cell-ba

235 Apelin receptor (Aplnr) and its endogenous ligand apelin

236 The apelin receptor (APLNR) is a GPCR involved in many patho

237 The Apelin receptor (Aplnr) is essential for heart developme

238 genetic and epigenetic regulation of apelin, apelin receptor (APLNR), and endothelial nitric oxide sy

239 r transcripts encoding the G-protein-coupled APELIN receptor (APLNR).

240 ed markedly reduced transcripts encoding the apelin receptor (Micu2(-/-) vs. wild type, P = 7.8 x 10(

241 Several reports suggest apelin receptor activation with apelin peptides results

242 Treatment with an apelin receptor agonist after vasculopathy was establish

243 In vitro, an apelin receptor agonist analog elicited endothelial nitr

244 ovides additional proof of principle that an apelin receptor agonist may be of therapeutic use in PAH

245 6 (1) was described as the first nonpeptidic apelin receptor agonist.

246 velopment of metabolically stable ligands of apelin receptor and their effects in various models over

247 , which was blocked by pretreatment with the apelin receptor antagonist, F13A (0 +/- 1 mmHg; P < 0.01

248 e investigate the roles of the proangiogenic apelin receptor APLNR and its cognate ligand apelin in V

249 the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apeli

250 in JEG3 cells suppressed syncytin 1 (SYN-1), apelin receptor early endogenous ligand (ELABELA), and t

251 deleted), which exhibit opposite profiles on apelin receptor internalization and BP.

252 f apelin 17 (K17F) is crucial for triggering apelin receptor internalization and decreasing blood pre

253 show that both beta-arrestin recruitment and apelin receptor internalization contribute to the K17F-s

254 agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased

255 Apelin peptides and the apelin receptor represent a relatively new therapeutic a

256 receptor as well as its capacity to promote apelin receptor signaling and internalization.

257 r show that during this angioblast migration Apelin receptor signaling is mainly triggered by the rec

258 indicate that Toddler is an activator of APJ/Apelin receptor signaling, promotes gastrulation movemen

259 1 and a concomitant decrease in vasodilatory apelin receptor signaling.

260 The apelin receptor system is a pleiotropic pathway with a p

261 tagonists to more rigorously interrogate the apelin receptor system.

262 onally, selective competitive antagonists of apelin receptor were shown to be safe and effective in r

263 Protamine is an antagonist of apelin receptor, and its activity is reversed by heparin

264 tide that acts through the G-protein-coupled apelin receptor, despite lack of sequence similarity to

265 at ELA is an endogenous agonist of the human apelin receptor, exhibits a cardiovascular profile compa

266 of-function mutations in APLNR, encoding the apelin receptor, in patient tumours that were refractory

267 bioavailable agonists and antagonists of the apelin receptor, is crucial.

268 armacology and the physiological role of the apelin receptor, the development of small, bioavailable

269 heart and signaling in cells expressing the apelin receptor.

270 blasts rely on their intrinsic expression of Apelin receptors (Aplr, APJ) for their migration to the

271 ves internalization of G protein-coupled APJ/Apelin receptors, and activation of APJ/Apelin signaling

272 In the lumen, active apelin regulates carbohydrate flux through enterocytes b

273 It is also found that apelin relieves the TNFalpha inhibition on brown adipoge

274 Among the several studied polymorphisms, apelin rs3761581, rs2235312, and rs3115757; APLNR rs1154

275 cells; we studied whether glucose modulates apelin secretion by enterocytes and the effects of apeli

276 We characterized glucose-related luminal apelin secretion in vivo and ex vivo by mass spectroscop

277 men to the bloodstream by increasing luminal apelin secretion.

278 Mechanistically, Apelin signaling enhances glycolytic activity in ECs at

279 Zebrafish lacking Apelin signaling exhibit defects in endothelial tip cell

280 Here, we show that Apelin signaling functions to drive ECs into such an ang

281 However, the role of apelin signaling in stem cell recruitment after ischemia

282 lmonary arterial hypertension (PAH) in which apelin signaling is downregulated, and to demonstrate at

283 Apelin signaling plays an important role during embryo d

284 w vessels while neighboring ECs defective in Apelin signaling remain in the DA.

285 APJ/Apelin receptors, and activation of APJ/Apelin signaling rescues toddler mutants.

286 tal principles of blood vessel formation and Apelin signaling, enabling a better understanding of vas

287 Whereas apelin stimulates APJ to activate Galphai and elicits a

288 To the contrary, apelin suppressed autophagic cell death during reoxygena

289 However, aberrations in the apelin system impair pulmonary vascular function, potent

290 demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the ape

291 In contrast, mice lacking apelin (the endogenous APJ ligand) remain sensitive, sug

292 gonistic interaction between PRR and ELABELA/apelin, the mutually stimulatory relationship between PR

293 the present study, we provide evidence that apelin, through its interaction with apelin receptor (AP

294 Indirect calorimetry experiments showed that apelin-treated mice had a better use of lipids.

295 ll the effects studied were abrogated in HFD apelin-treated mice with muscle-specific inactive AMPK.

296 drial biogenesis were increased in soleus of apelin-treated mice.

297 Apelin treatment also increased cardiac contractility an

298 Both acute and chronic apelin treatment have been shown to improve insulin sens

299 Moreover, apelin, via activation of its receptor, APJ, increased A

300 The action of apelin was AMP-activated protein kinase (AMPK) dependent