View source for Apelin

{{Infobox_gene}}

'''Apelin''' (also known as '''APLN''') is a peptide that in humans is encoded by the ''APLN'' gene.<ref name="Tatemoto_1998">{{cite journal |vauthors=Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, Kawamata Y, Fukusumi S, Hinuma S, Kitada C, Kurokawa T, Onda H, Fujino M | title = Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor | journal = Biochem. Biophys. Res. Commun. | volume = 251 | issue = 2 | pages = 471–6 | year = 1998 | pmid = 9792798 | doi = 10.1006/bbrc.1998.9489 }}</ref> Apelin is the endogenous [[ligand]] for the [[G-protein]]-coupled [[apelin receptor|APJ receptor]]<ref name="Lee_2000">{{cite journal |vauthors=Lee DK, Cheng R, Nguyen T, Fan T, Kariyawasam AP, Liu Y, Osmond DH, George SR, O'Dowd BF | title = Characterization of apelin, the ligand for the APJ receptor | journal = J. Neurochem. | volume = 74 | issue = 1 | pages = 34–41 | year = 2000 | pmid = 10617103 | doi = 10.1046/j.1471-4159.2000.0740034.x }}</ref><ref name="pmid12215493">{{cite journal |vauthors=Szokodi I, Tavi P, Földes G, Voutilainen-Myllylä S, Ilves M, Tokola H, Pikkarainen S, Piuhola J, Rysä J, Tóth M, Ruskoaho H | title = Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility | journal = Circ. Res. | volume = 91 | issue = 5 |pages = 434–40 | year = 2002 | pmid = 12215493 | doi = 10.1161/01.RES.0000033522.37861.69}}</ref><ref name="pmid15907343">{{cite journal |vauthors=Kleinz MJ, Davenport AP | title = Emerging roles of apelin in biology and medicine | journal = Pharmacol. Ther. | volume = 107 | issue = 2 |pages = 198–211 | year = 2005 | pmid = 15907343 | doi = 10.1016/j.pharmthera.2005.04.001 }}</ref><ref name="pmid8294032">{{cite journal |vauthors=O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T | title = A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11 | journal = Gene | volume = 136 | issue = 1–2 | pages = 355–60 |date=December 1993 | pmid = 8294032 | doi = 10.1016/0378-1119(93)90495-O| url = }}</ref><ref name="pmid8951791">{{cite journal |vauthors=Devic E, Paquereau L, Vernier P, Knibiehler B, Audigier Y | title = Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis | journal = Mech. Dev. | volume = 59 | issue = 2 | pages = 129–40 |date=October 1996 | pmid = 8951791 | doi = 10.1016/0925-4773(96)00585-0| url = }}</ref> that is expressed at the surface of some cell types.<ref name = "Audigier_2006">{{cite web | author = Audigier Y | title = Apelin Receptor | url  = http://www.signaling-gateway.org/molecule/query?afcsid=A000304&amp;mpv=1 | work  = UCSD-Nature Molecule Pages | publisher = Nature Publishing Group | doi = 10.1038/mp.a000304.01 | date = 2006-04-07| accessdate  = 2009-09-02| quote = }}</ref> It is widely expressed in various organs such as the heart, lung, kidney, liver, [[adipose tissue]], [[gastrointestinal tract]], brain, adrenal glands, [[endothelium]], and human [[blood plasma|plasma]].

== Discovery ==

Apelin is a peptide that was identified in 1998 by Professor M. Fujino’s team.<ref name="Tatemoto_1998" />

== Biosynthesis ==

Apelin gene encodes a pre-proprotein of 77 amino acids,<ref name="Tatemoto_1998" /> with a [[signal peptide]] in the [[N-terminus|N-terminal]] region. After translocation into the [[endoplasmic reticulum]] and cleavage of the signal peptide, the proprotein of 55 amino acids may generate several active fragments: a 36 amino acid peptide corresponding to the sequence 42-77 (apelin 36), a 17 amino acid peptide corresponding to the sequence 61-77 (apelin 17) and a 13 amino acid peptide corresponding to the sequence 65-77 (apelin 13). This latter fragment may also undergo a pyroglutamylation at the level of its N-terminal glutamine residue. However the presence and/or the concentrations of those peptides in human plasma has been questioned.<ref name="pmid20857448">{{cite journal |vauthors=Mesmin C, Dubois M, Becher F, Fenaille F, Ezan E | title = Liquid chromatography/tandem mass spectrometry assay for the absolute quantification of the expected circulating apelin peptides in human plasma | journal = Rapid Commun Mass Spectrom | year = 2010 | volume = 24 | issue = 19 | pages = 2875–84 | pmid = 20857448 | doi = 10.1002/rcm.4718 }}</ref> Recently, 46 different apelin peptides ranging from apelin 55 (proapelin) to apelin 12 have been identified in bovine colostrum, including C-ter truncated isoforms.<ref name="pmid21939284">{{cite journal |vauthors=Mesmin C, Fenaille F, Becher F, Tabet JC, Ezan E | title = Identification and characterization of apelin peptides in bovine colostrum and milk by liquid chromatography-mass spectrometry. | journal = J Proteome Res | year = 2011 | pmid = 21939284 | doi = 10.1021/pr200725x | volume=10 | issue=11 | pages=5222–31}}</ref>

== Physiological functions ==

The sites of receptor expression are clearly linked to the different functions played by apelin in the organism.

=== Vascular ===

Vascular expression of the receptor<ref name="Devic_1999">{{cite journal |vauthors=Devic E, Rizzoti K, Bodin S, Knibiehler B, Audigier Y | title = Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ | journal = Mech. Dev. | volume = 84 | issue = 1–2 | pages = 199–203 |date=June 1999 | pmid = 10473142 | doi = 10.1016/S0925-4773(99)00081-7| url = }}</ref><ref name="Saint-Geniez_2002">{{cite journal |vauthors=Saint-Geniez M, Masri B, Malecaze F, Knibiehler B, Audigier Y | title = Expression of the murine msr/apj receptor and its ligand apelin is upregulated during formation of the retinal vessels | journal = Mech. Dev. | volume = 110 | issue = 1–2 | pages = 183–6 |date=January 2002 | pmid = 11744380 | doi = 10.1016/S0925-4773(01)00558-5| url = }}</ref> participates in the control of [[blood pressure]]<ref name="Lee_2000"/> and its activation promotes the formation of new blood vessels ([[angiogenesis]]).<ref name="Saint-Geniez_2002"/><ref name="Masri_2004">{{cite journal |vauthors=Masri B, Morin N, Cornu M, Knibiehler B, Audigier Y | title = Apelin (65-77) activates p70 S6 kinase and is mitogenic for umbilical endothelial cells | journal = FASEB J. | volume = 18 | issue = 15 | pages = 1909–11 |date=December 2004 | pmid = 15385434 | doi = 10.1096/fj.04-1930fje | url = }}</ref><ref name="Kasai_2004">{{cite journal |vauthors=Kasai A, Shintani N, Oda M, Kakuda M, Hashimoto H, Matsuda T, Hinuma S, Baba A | title = Apelin is a novel angiogenic factor in retinal endothelial cells | journal = Biochem. Biophys. Res. Commun. | volume = 325 | issue = 2 | pages = 395–400 |date=December 2004 | pmid = 15530405 | doi = 10.1016/j.bbrc.2004.10.042 | url = }}</ref><ref name="pmid16750822">{{cite journal |vauthors=Cox CM, D'Agostino SL, Miller MK, Heimark RL, Krieg PA | title = Apelin, the ligand for the endothelial G-protein-coupled receptor, APJ, is a potent angiogenic factor required for normal vascular development of the frog embryo | journal = Dev. Biol. | volume = 296 | issue = 1 | pages = 177–89 |date=August 2006 | pmid = 16750822 | doi = 10.1016/j.ydbio.2006.04.452 | url = }}</ref>  The [[hypotensive]] effect of apelin results from the activation of receptors expressed at the surface of [[endothelial cells]].<ref name="Devic_1999"/><ref name="Saint-Geniez_2002"/> This activation induces the release of NO,<ref name="pmid11384769">{{cite journal |vauthors=Tatemoto K, Takayama K, Zou MX, Kumaki I, Zhang W, Kumano K, Fujimiya M | title = The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism | journal = Regul. Pept. | volume = 99 | issue = 2–3 | pages = 87–92 |date=June 2001 | pmid = 11384769 | doi = 10.1016/S0167-0115(01)00236-1| url = }}</ref> a potent vasodilator, which induces relaxation of the smooth muscle cells of artery wall. Studies performed on mice  knocked out for the apelin receptor gene<ref name="pmid15087458">{{cite journal |vauthors=Ishida J, Hashimoto T, Hashimoto Y, Nishiwaki S, Iguchi T, Harada S, Sugaya T, Matsuzaki H, Yamamoto R, Shiota N, Okunishi H, Kihara M, Umemura S, Sugiyama F, Yagami K, Kasuya Y, Mochizuki N, Fukamizu A | title = Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo | journal = J. Biol. Chem. | volume = 279 | issue = 25 | pages = 26274–9 |date=June 2004 | pmid = 15087458 | doi = 10.1074/jbc.M404149200 | url = }}</ref> have suggested the existence of a balance between [[angiotensin II]] signalling, which increases blood pressure and apelin signalling, which lowers blood pressure.  The [[angiogenic]] activity is the consequence of apelin action on the proliferation and migration of the endothelial cells. Apelin activates inside the cell transduction cascades (ERKs, Akt, and p70S6kinase phosphorylation),<ref name="Masri_2004"/><ref name="pmid11779205">{{cite journal |vauthors=Masri B, Lahlou H, Mazarguil H, Knibiehler B, Audigier Y | title = Apelin (65-77) activates extracellular signal-regulated kinases via a PTX-sensitive G protein | journal = Biochem. Biophys. Res. Commun. | volume = 290 | issue = 1 | pages = 539–45 |date=January 2002 | pmid = 11779205 | doi = 10.1006/bbrc.2001.6230 | url = }}</ref> which lead to the proliferation of endothelial cells and the formation of new blood vessels.<ref name="Kasai_2004"/> Knockout of the apelin gene is associated with a delay in the development of the retinal vasculature.<ref name="pmid18599802">{{cite journal |vauthors=Kasai A, Shintani N, Kato H, Matsuda S, Gomi F, Haba R, Hashimoto H, Kakuda M, Tano Y, Baba A | title = Retardation of retinal vascular development in apelin-deficient mice | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 28 | issue = 10 | pages = 1717–22 |date=October 2008 | pmid = 18599802 | doi = 10.1161/ATVBAHA.108.163402 | url = }}</ref>

=== Cardiac ===

The apelin receptor is expressed early during the [[embryonic development]] of the heart, where it regulates the migration of cell progenitors fated to differentiate into [[cardiomyocytes]],  the contractile cells of the heart.<ref name="pmid17336906">{{cite journal |vauthors=Scott IC, Masri B, D'Amico LA, Jin SW, Jungblut B, Wehman AM, Baier H, Audigier Y, Stainier DY | title = The g protein-coupled receptor agtrl1b regulates early development of myocardial progenitors | journal = Dev. Cell | volume = 12 | issue = 3 | pages = 403–13 |date=March 2007 | pmid = 17336906 | doi = 10.1016/j.devcel.2007.01.012 | url = }}</ref><ref name="pmid17336905">{{cite journal |vauthors=Zeng XX, Wilm TP, Sepich DS, Solnica-Krezel L | title = Apelin and its receptor control heart field formation during zebrafish gastrulation | journal = Dev. Cell | volume = 12 | issue = 3 | pages = 391–402 |date=March 2007 | pmid = 17336905 | doi = 10.1016/j.devcel.2007.01.011 | url = }}</ref> Its expression is also detected in the cardiomyocytes of the adult where apelin behaves as one of the most potent stimulator of cardiac contractility.<ref name="pmid12215493"/><ref name="pmid15364861">{{cite journal |vauthors=Berry MF, Pirolli TJ, Jayasankar V, Burdick J, Morine KJ, Gardner TJ, Woo YJ | title = Apelin has in vivo inotropic effects on normal and failing hearts | journal = Circulation | volume = 110 | issue = 11 Suppl 1 | pages = II187–93 |date=September 2004 | pmid = 15364861 | doi = 10.1161/01.CIR.0000138382.57325.5c | url = }}</ref><ref name="pmid15621035">{{cite journal |vauthors=Ashley EA, Powers J, Chen M, Kundu R, Finsterbach T, Caffarelli A, Deng A, Eichhorn J, Mahajan R, Agrawal R, Greve J, Robbins R, Patterson AJ, Bernstein D, Quertermous T | title = The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo | journal = Cardiovasc. Res. | volume = 65 | issue = 1 | pages = 73–82 |date=January 2005 | pmid = 15621035 | pmc = 2517138 | doi = 10.1016/j.cardiores.2004.08.018 | url = }}</ref> Aged apelin knockout mice develop progressive impairment of cardiac contractility.<ref name="pmid17673668">{{cite journal |vauthors=Kuba K, Zhang L, Imai Y, Arab S, Chen M, Maekawa Y, Leschnik M, Leibbrandt A, Markovic M, Makovic M, Schwaighofer J, Beetz N, Musialek R, Neely GG, Komnenovic V, Kolm U, Metzler B, Ricci R, Hara H, Meixner A, Nghiem M, Chen X, Dawood F, Wong KM, Sarao R, Cukerman E, Kimura A, Hein L, Thalhammer J, Liu PP, Penninger JM | title = Impaired heart contractility in Apelin gene-deficient mice associated with aging and pressure overload | journal = Circ. Res. | volume = 101 | issue = 4 | pages = e32–42 |date=August 2007 | pmid = 17673668 | doi = 10.1161/CIRCRESAHA.107.158659 | url = }}</ref>  Apelin acts as a mediator of the cardiovascular control, including for blood pressure and blood flow. It is one of the most potent stimulators of cardiac [[contractility]] yet identified, and plays a role in cardiac tissue remodeling. Apelin levels are increased in left ventricles of patients with chronic heart failure and also in patients with [[chronic liver disease]].<ref name="pmid18816630">{{cite journal |vauthors=Principe A, Melgar-Lesmes P, Fernández-Varo G, Del Arbol LR, Ros J, Morales-Ruiz M, Bernardi M, Arroyo V, Jiménez W | title = The hepatic apelin system: A new therapeutic target for liver disease | journal = Hepatology | volume = 48 | issue = 4 | pages = 1193–1201 | year = 2008 | pmid = 18816630 | doi = 10.1002/hep.22467 }}</ref>

=== Exercise ===

The plasma concentration of apelin is shown to increase during exercise.<ref name="zzzz">{{cite journal |vauthors=Kechyn S,Barnes G, Howard L| title = Assessing dynamic changes in plasma apelin concentration in response to maximal exercise in man | journal = European Respiratory Journal |year=2015 |volume=46 |page=PA2316 |  doi = 10.1183/13993003.congress-2015.PA2316}}</ref>. Paradoxically,exogenous apelin in healthy volunteers reduced peak VO2 in an endurance test.<ref>{{cite journal |last1=Kechyn |first1=Svyatoslav |last2=Barnes |first2=Gareth |last3=Thongmee |first3=Akaphot |last4=Howard |first4=Luke |title=Effect of apelin on cardiopulmonary performance during endurance exercise |journal=European Respiratory Journal |date=September 2015 |issue=46 suppl 59 |pages=2241 |doi=10.1183/13993003.congress-2015.PA2241}}</ref>

=== Brain ===

Apelin receptor is also expressed in the neurons of brain areas involved in regulating water and food intake.<ref name="Lee_2000"/><ref name="pmid11004481">{{cite journal |vauthors=O'Carroll AM, Selby TL, Palkovits M, Lolait SJ | title = Distribution of mRNA encoding B78/apj, the rat homologue of the human APJ receptor, and its endogenous ligand apelin in brain and peripheral tissues | journal = Biochim. Biophys. Acta | volume = 1492 | issue = 1 | pages = 72–80 |date=June 2000 | pmid = 11004481 | doi = 10.1016/S0167-4781(00)00072-5| url = }}</ref><ref>De Mota et al., 2000</ref> Apelin injection increases water intake<ref name="Lee_2000"/> and apelin decreases the [[hypothalamus|hypothalamic]] secretion of the [[diuresis|antidiuretic]] [[hormone]] [[vasopressin]].<ref name="pmid11146423">{{cite journal |vauthors=De Mota  N, Lenkei Z, Llorens-Cortès C | title = Cloning, pharmacological characterization and brain distribution of the rat apelin receptor | journal = Neuroendocrinology | volume = 72 | issue = 6 | pages = 400–7 |date=December 2000 | pmid = 11146423 | doi = 10.1159/000054609| url = }}</ref> This [[diuretic]] effect of apelin in association with its hypotensive effect participates in the homeostatic regulation of body fluid.  Apelin is also detected in brain areas which control appetite, but its effects on food intake are very contradictory.<ref name="pmid11883945">{{cite journal |vauthors=Taheri S, Murphy K, Cohen M, Sujkovic E, Kennedy A, Dhillo W, Dakin C, Sajedi A, Ghatei M, Bloom S | title = The effects of centrally administered apelin-13 on food intake, water intake and pituitary hormone release in rats | journal = Biochem. Biophys. Res. Commun. | volume = 291 | issue = 5 | pages = 1208–12 |date=March 2002 | pmid = 11883945 | doi = 10.1006/bbrc.2002.6575 | url = }}</ref><ref name="pmid14642423">{{cite journal |vauthors=Sunter D, Hewson AK, Dickson SL | title = Intracerebroventricular injection of apelin-13 reduces food intake in the rat | journal = Neurosci. Lett. | volume = 353 | issue = 1 | pages = 1–4 |date=December 2003 | pmid = 14642423 | doi = 10.1016/S0304-3940(03)00351-3| url = }}</ref><ref name="pmid12793520">{{cite journal |vauthors=O'Shea M, Hansen MJ, Tatemoto K, Morris MJ | title = Inhibitory effect of apelin-12 on nocturnal food intake in the rat | journal = Nutr Neurosci | volume = 6 | issue = 3 | pages = 163–7 |date=June 2003 | pmid = 12793520 | doi = 10.1080/1028415031000111273| url = }}</ref>

===Adipose tissue===
Apelin is expressed and secreted by [[adipocyte]]s, and its production is increased during adipocyte differentiation and is stimulated by [[insulin]].<ref name="Boucher2005">{{cite journal|vauthors=Boucher J, Masri B, Daviaud D, Gesta S, Guigné C, Mazzucotelli A, Castan-Laurell I, Tack I, Knibiehler B, Carpéné C, Audigier Y, Saulnier-Blache JS, Valet P|title=Apelin, a newly identified adipokine up-regulated by insulin and obesity|journal=Endocrinology |date=April 2005|volume=146|issue=4|pages=1764–71|doi=10.1210/en.2004-1427|pmid=15677759|url=http://press.endocrine.org/doi/full/10.1210/en.2004-1427|accessdate=30 June 2016}}</ref> Most obese people have elevated levels of insulin, which may therefore be the reason why obese people have been reported to also have elevated levels of apelin.<ref name="Boucher2005"/>

=== Digestive ===

Apelin receptor is expressed in several cell types of the [[gastro-intestinal tract]] : [[stomach]] enterochromaffine-like cells;<ref name="pmid14670994">{{cite journal |vauthors=Wang G, Anini Y, Wei W, Qi X, OCarroll AM, Mochizuki T, Wang HQ, Hellmich MR, Englander EW, Greeley GH | title = Apelin, a new enteric peptide: localization in the gastrointestinal tract, ontogeny, and stimulation of gastric cell proliferation and of cholecystokinin secretion | journal = Endocrinology | volume = 145 | issue = 3 | pages = 1342–8 |date=March 2004 | pmid = 14670994 | doi = 10.1210/en.2003-1116 | url = }}</ref><ref name="Lambrecht_2006">{{cite journal |vauthors=Lambrecht NW, Yakubov I, Zer C, Sachs G | title = Transcriptomes of purified gastric ECL and parietal cells: identification of a novel pathway regulating acid secretion | journal = Physiol. Genomics | volume = 25 | issue = 1 | pages = 153–65 |date=March 2006 | pmid = 16403840 | doi = 10.1152/physiolgenomics.00271.2005 | url = }}</ref> unknown cells of endocrine [[pancreas]],<ref name="Sorhede Winzell et al., 2005">Sorhede Winzell et al., 2005</ref> [[Colon (anatomy)|colon]] epithelial cells.<ref name="pmid19660504">{{cite journal |vauthors=Wang G, Kundu R, Han S, Qi X, Englander EW, Quertermous T, Greeley GH | title = Ontogeny of apelin and its receptor in the rodent gastrointestinal tract | journal = Regul. Pept. | volume = 158| issue = 1–3| pages = 32–9|date=August 2009 | pmid = 19660504 | doi = 10.1016/j.regpep.2009.07.016 | url = | pmc = 2761510 }}</ref>
In stomach, activation of receptors on enterochromaffine-like cells by apelin secreted by [[parietal cells]] can inhibit histamine release by enterochromaffine-like cells, which in turn decreases acid secretion by parietal cells.<ref name="Lambrecht_2006"/> In pancreas, apelin inhibits  the insulin secretion induced by glucose.<ref name="pmid15970338">{{cite journal |vauthors=Sörhede Winzell M, Magnusson C, Ahrén B | title = The apj receptor is expressed in pancreatic islets and its ligand, apelin, inhibits insulin secretion in mice | journal = Regul. Pept. | volume = 131 | issue = 1–3 | pages = 12–7 |date=November 2005 | pmid = 15970338 | doi = 10.1016/j.regpep.2005.05.004 | url = }}</ref> This inhibition reveals the functional interdependency between apelin signalling and insulin signalling observed at the adipocyte level where insulin stimulate apelin production.<ref name="Boucher2005"/> Recently, receptor expression was also detected in skeletic muscle cells. Its activation is involved in glucose uptake and participates in the control of glucose blood levels [[Blood sugar|glycemia]].<ref name="pmid19046574">{{cite journal |vauthors=Dray C, Knauf C, Daviaud D, Waget A, Boucher J, Buléon M, Cani PD, Attané C, Guigné C, Carpéné C, Burcelin R, Castan-Laurell I, Valet P | title = Apelin stimulates glucose utilization in normal and obese insulin-resistant mice | journal = Cell Metab. | volume = 8 | issue = 5 | pages = 437–45 |date=November 2008 | pmid = 19046574 | doi = 10.1016/j.cmet.2008.10.003 | url = }}</ref>

=== Bone ===

Receptor expression is also observed at the surface of osteoblasts, the cell progenitors involved in bone formation.<ref name="pmid16563531">{{cite journal |vauthors=Xie H, Tang SY, Cui RR, Huang J, Ren XH, Yuan LQ, Lu Y, Yang M, Zhou HD, Wu XP, Luo XH, Liao EY | title = Apelin and its receptor are expressed in human osteoblasts | journal = Regul. Pept. | volume = 134 | issue = 2–3 | pages = 118–25 |date=May 2006 | pmid = 16563531 | doi = 10.1016/j.regpep.2006.02.004 | url = }}</ref>

=== Muscle aging ===

Muscle apelin expression decreases with age in rodents and humans<ref name="vinel_2018">{{cite journal |last1=Vinel |first1=Claire |last2=Lukjanenko |first2=Laura |last3=Batut |first3=Aurelie |last4=Deleruyelle |first4=Simon |last5=Pradère |first5=Jean-Philippe |last6=Le Gonidec |first6=Sophie |last7=Dortignac |first7=Allizée |last8=Geoffre |first8=Nancy |last9=Pereira |first9=Ophélie |last10=Karaz |first10=Sonia |last11=Lee |first11=Umi |last12=Camus |first12=Mylène |last13=Chaoui |first13=Karima |last14=Mouisel |first14=Etienne |last15=Bigot |first15=Anne |last16=Mouly |first16=Vincent |last17=Vigneau |first17=Mathieu |last18=Pagano |first18=Allan |last19=Chopard |first19=Angèle |last20=Pillard |first20=Fabien |last21=Guyonnet |first21=Sophie |last22=Cesari |first22=Matteo |last23=Burlet |first23=Odile |last24=Pahor |first24=Marco |last25=Feige |first25=Jerome |last26=Vellas |first26=Bruno |last27=Valet |first27=Philippe |last28=Dray |first28=Cedric |title=The exerkine apelin reverses age-associated sarcopenia. |journal=Nature Medicine |date=30 July 2018 |doi=10.1038/s41591-018-0131-6 |pmid=30061698 }}</ref>. By supplementing aged mice with exogenous apelin, the team of Dr C. Dray shown that the peptide was able to promote muscle hypertrophy and consequently induced a gain in strength<ref name="vinel_2018"/>. This study also demonstrated that apelin targets muscle cells during aging by different and complementary pathways:  it acts on muscle metabolism by activating an AMPK-dependent mitochondria biogenesis, it promotes autophagy and decreases inflammation in aged mice<ref name="vinel_2018"/>. Moreover, apelin receptor is also present on muscle stem cells and promotes in vitro and in vivo proliferation and differenciation of these cells into mature muscle cells participating to muscle regeneration. Finally, muscle apelin could be used a biomarker of physical exercise success in aged individual since its production is corelated to the benefit of a chronic physical exercise in aged individuals<ref name="vinel_2018"/>.

== References ==
{{Reflist|30em}}

==Further reading==
{{refbegin | colwidth = 30em}}

* {{cite journal |vauthors=Lee DK, George SR, O'Dowd BF | title = Unravelling the roles of the apelin system: prospective therapeutic applications in heart failure and obesity | journal = Trends Pharmacol. Sci. | volume = 27 | issue = 4 | pages = 190–4 | year = 2006 | pmid = 16530855 | doi = 10.1016/j.tips.2006.02.006 }}
* {{cite journal |vauthors=Lee DK, Saldivia VR, Nguyen T, Cheng R, George SR, O'Dowd BF | title = Modification of the terminal residue of apelin-13 antagonizes its hypotensive action | journal = Endocrinology | volume = 146 | issue = 1 | pages = 231–6 | year = 2005 | pmid = 15486224 | doi = 10.1210/en.2004-0359 }}
* {{cite journal |vauthors=Lee DK, Lança AJ, Cheng R, Nguyen T, Ji XD, Gobeil F, Chemtob S, George SR, O'Dowd BF | title = Agonist-independent nuclear localization of the Apelin, angiotensin AT1, and bradykinin B2 receptors | journal = J. Biol. Chem. | volume = 279 | issue = 9 | pages = 7901–8 | year = 2004 | pmid = 14645236 | doi = 10.1074/jbc.M306377200 }}
* {{cite journal |vauthors=O'Dowd BF, Heiber M, Chan A, Heng HH, Tsui LC, Kennedy JL, Shi X, Petronis A, George SR, Nguyen T | title = A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11 | journal = Gene | volume = 136 | issue = 1–2 | pages = 355–60 | year = 1993 | pmid = 8294032 | doi = 10.1016/0378-1119(93)90495-O }}
* {{cite journal |vauthors=Chun HJ, Ali ZA, Kojima Y, Kundu RK, Sheikh AY, Agrawal R, Zheng L, Leeper NJ, Pearl NE, Patterson AJ, Anderson JP, Tsao PS, Lenardo MJ, Ashley EA, Quertermous T | title = Apelin signaling antagonizes Ang II effects in mouse models of atherosclerosis | journal = The Journal of Clinical Investigation | volume = 118 | issue = 10 | pages = 3343–54 |date=October 2008 | pmid = 18769630 | pmc = 2525695 | doi = 10.1172/JCI34871 }}
* {{cite journal |vauthors=Barnes G, Japp AG, Newby DE | title = Translational promise of the apelin--APJ system | journal = Heart | volume = 96 | issue = 13 | pages = 1011–6 |date=July 2010 | pmid = 20584856 | doi = 10.1136/hrt.2009.191122 }}

{{refend}}

==External links==
*{{MeshName|Apelin+protein,+human}}
* {{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1329 | title = Apelin | accessdate = | date = | format = | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | pages = | language = | archiveurl = | archivedate = | quote = }}
* {{UCSC gene info|APLN}}

[[Category:Proteins]]