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am 25 dez bifo
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
Difinishɔn fɔ AOD9604
AOD9604 na pεptida we kכmכt frכm di C-tεrminal fragmεnt fכ di hכmon gכt hכmon (hGH). i kכnsis fכ amino asid 177–191 fכ hGH, wit wan adishכnal tayrozin rεsidεns (Tyr) we dεn ad na di N-tεrminal εnd fכ di pεptida, dat na, Tyr-hGH 177–191. di amino asid sikεns fכ AOD9604 de ditarεmin in spatial kכnfכmeshכn, we in tכn de infכlכp in intarakshכn wit difrεn risεptor dεm εn mכlikul dεm na di bכdi. di tayrosin rεsidεns we dεn ad na di N-tεrminus kin afekt di stεbiliti fכ di pεptida insay di bכdi, sεl כptek efyushכn, εn binding afiniti wit spεsifi k rεsεpכta dεm. AOD9604 de pan di klas fכ pεptida kכmpawnd dεm, we de tek pat pan difrεn fysiolojikal prכsεs dεm na di bכdi, lεk signal transdyushכn εn mεtabolik rεguleshכn. fכ in spεsifi k כrijin εn strכkchכ, AOD9604 posεs yunik fysiolojikal fכnshכn dεm, patikyuכl we de sho sכm ifekt dεm insay lipid mεtabolism rεguleshכn.
Mekanism fכ AOD9604 in Rεgulεt Lipid Mεtabolism
(1) Asosieshɔn wit di β-adrenergic path
rεguleshכn fכ β-adrenergic rεsεptכr εksprεshכn: AOD9604 kin infכlכw lipid mεtabolism bay we i de intarakt wit di β-adrenergic path, patikyular tru di rεguleshכn fכ di β(3)-adrenergic rεsεpכta (β(3)-AR). insay wan obes maws mכdel, afta 14 kכnsekyutiv de dεm we dεn injεk AOD9604 insay pεritonial, di εksprεshכn lεvεl fכ β(3)-AR RNA insay adiposyt dεm inkrεs. di β(3)-AR na di praymar lipolytic risεptor insay adiposyt dεm, εn in inkrεs εksprεshכn de protεkt lipolysis. AOD9604 kin εnhans di εksprεshכn fכ di β(3)-AR jin bay we i de aktibכt rilayt signal path dεm, we de inkrεs in sכfayz εksprεshכn insay sεl dεm. i kin infכlכw di binding fכ sכm transkripshכn fכktכ dεm to di prכmot rijyכn fכ di β(3)-AR jin, we de εnhans di efyushכn fכ jin transkripshכn initiashכn.
di kaskad riakshכn dεm fכ β-adrenergic pathway aktibכshכn: we β(3)-AR εksprεshכn de inkrεs, i de biεn to ligεnd dεm fכ aktibכt dכwnstrim signal path dεm. aktibכt β(3)-AR de kכpl wit G protin dεm, we de lid to di aktibכshכn fכ adenylate cyclase, we in tכn de inkrεs di intasεlulyar lεvεl dεm fכ di sεkכn mεsenja sayklik adenosin monofכsfεt (cAMP). cAMP de aktibכt protin kinaz A (PKA), we de fכsfכraylet εn aktibכt כmon-sεnsitiv laypas (HSL), we na wan kכl εnzym insay lipolysis we de katalayz di haydrolis fכ triglisεrayd dεm to fεt asid εn glisεrol, we de protεkt lipolysis εn rεgεl di lipid mεtabolism.
(2) Dairekt ifekt dεm indipεndεnt frכm β(3)-AR
Akyu εkspεriεns fכndεns: Insay akyu εkspεriεns wit β(3)-AR jin-kכkכt mays, AOD9604 stil inkrεs εnεji εkspεndishכn εn fεt כksidεshכn. dis sho se AOD9604 in rεgεdyushכn ifekt pan lipid mεtabolism nכ de dipεnd כlsay pan β(3)-AR. pan tap we dεn nכ כndastand di spεsifi k mεkanism yet, כda path dεm כ dairekt akshכn tכgεt dεm kin de. AOD9604 kin akt dairekt pan maytochכndria, infכlכw di maytochכndria fכnshכn εn εnhans di β-oksidashכn fכ fεt asid dεm. di maytochכndria dεm na di sεntri hab dεm fכ di sεlyul enεji mεtabolism, εn fεt asid β-oksidashכn de apin insay di maytochכndria. AOD9604 kin promuot fεt asid εntri insay maytochכndria εn fεsilit כksidεtiv dεgradashכn bay we i de rεgεl di aktvכti fכ transpכt protin dεm כ riletid εnzym dεm na di maytochכndrial mεmbran, we de mek i inkrεs εnεji εn fεt asid כksidεshכn.
pכtεnshal adishכnal signal path dεm: AOD9604 de involv bak fכ rεgεl כda signal path dεm. i kin infכlכw di aktiviti fכ di pεrכksisom proliferator-aktivεt rεsεpכta (PPAR) famili. PPAR dεm na wan klas fכ nyuklia rεsεpכta dεm we de ple imכtant rεgεdyushכn rol insay lipid mεtabolism, εnεji bεlε, εn inflammatory rεspכns dεm. AOD9604 kin intarakt wit PPAR dεm fכ rεgεl di εksprεshכn fכ dεn tכgεt jin dεm, we de afekt di transkripshכn εn transleshכn fכ di lipid mεtabolism-rεlatεd jin dεm, we de rεgεl di lipid mεtabolism. i kin tek pat bak pan di rεguleshכn fכ di insulin signal path. pan ɔl we AOD9604 nɔ gɛt di sayd ifɛkt dɛn we de mek pɔsin gɛt dayabitis we gɛt fɔ du wit hGH, i kin indaykt wan inflɔws di lipid mɛtabolism prɔses bay we i de fayn-tyu di insulin signal path.
Di Effekt dɛn we AOD9604 gɛt
(1) Ifɛkt pan di bɔdi wet ɛn fat
Animal εkspεriεns pruf: Insay wan obes maws mכdel, lכng tεm intrapεritכnial injεkshכn fכ AOD9604 (14 dez fכ krכnik administreshכn) sכmtεm rεdכks bכdi wet εn bכdi fεt kכntεnt. dis ridכkshכn pan bכdi wet εn fεt bin כsכsiayt wit inkrεs pan β(3)-AR RNA εksprεshכn lεvεl, we sho se AOD9604 de promuot lipolysis bay we i de rεgεl β(3)-AR εksprεshכn, we de achy rεdukshכn in bכdi wet εn bכdi fεt. sכm spεshal, di rεdukshכn bin de pan di sכbkutan εn vishכnal fεt wet, wit di כvala wet lכs. Durin di εkspεriεns, rεgulεr mεzhɔmεnt כf di maws wet εn prεsis post-mכtem mεjכmεnt כf fεt tisu wet rεvεl se AOD9604-trit mכs dεn sho signifyant rεdכks bכdi wet εn fεt wet kכmpεr to di kכntrol grup, wit dis rεdukshכn sho wan dכz-dipεndεnt tεnd.
Figure 2 Current ɛn Future Drug Targets in Weyt Manejmɛnt
Fɔ di tritmɛnt fɔ mɔtalman fat, di ifɛkt dɛm fɔ AOD9604 de ol pɔtɛnɛshɛl aplikeshɔn valyu. Fat na impɔtant tin we kin mek pɔsin gɛt bɔku sik dɛn we nɔ de mɛn lɛk sik dɛn we de mek pɔsin in at ɛn shuga, ɛn fɔ ridyus di bɔdi wet ɛn fat rili impɔtant fɔ mek di wan dɛn we fat gɛt wɛlbɔdi.
(2) Efεkt dεm pan εnεji mεtabolism
Inkrεs εnεji εkspεndishכn: AOD9604 de inkrεs εnεji εkspεndishכn in כl tu di nכmal mays dεm εn β(3)-AR jin kכnכt mays dεm. In nכmal mays, dεn yuz indaykt kalorimetri fכ mεzj כksijεn kכnsכmshכn εn kabכn dayכksayd prodakshכn, we sho se AOD9604 sכmtεm inkrεs εnεji mεtabolism rεt. dis ifekt de atribyut to AOD9604 we de promuot lipolysis, wit di rilis fεt asid dεm we de sεv as enεji sabstεrayt fכ כksidεshכn εn yutilizeshכn, we de inkrεs εnεji εkspεndishכn. In β(3)-AR knockout mice, although in mεkanism fכ akshכn nכ dipεnd pan β(3)-AR, inkrεs pan enεji εkspεndishכn bin stil obsεv, fכs sho se AOD9604 gεt εnεji mεtabolism rεguleshכn path we indipεndεnt frכm β(3)-AR.
rεgulεshכn fכ fεt כksidεshכn: AOD9604 de εnhans di fεt כksidεshכn prכsεs. insay sεlyul εkspεriεns, we dεn yuz rεdyuaktiv lεbul fεt asid fכ trak dεn כksidεtiv mεtabolism, dεn fכnshכn se di rεt fכ fεt asid כksidεshכn bin aksεlεrayt insay sεl dεm we dεn trit wit AOD9604. Dis nɔ jɔs de ɛp fɔ ridyus di fat we i de kip bɔt i de gi di bɔdi mɔ ɛnaji. AOD9604 kin εnhans fεt asid כksidεshכn efyushכn bay we i de rεgεl di maytochכndrial fכnshכn, inkrεs di maytochכndrial bayojεnεsis εn aktiviti. i de promuot di εksprεshכn εn aktvכti fכ di εnzym dεm we riliyt to fεt asid כksidεshכn insay maytochכndria, inklud di carnitine palmitoyltransferase I (CPT-I), we na di ki rεt-limitin εnzym fכ fεt asid dεm we de enta maytochכndria fכ כksidεshכn. AOD9604 kin promuot fεt asid εntri insay maytochכndria fכ כksidεtiv dεkכmכshכn bay we i de upregulate CPT-I εksprεshכn.
(3) Efεkt dεm pan di hεpatik lipid mεtabolism
di hεpatik lipid mεtabolism animal εkspεriεns stכdi: Insay wan maws fεt liva mכdel, dεn bin invεstigat di ifekt dεm we AOD9604 gεt pan hεpatik lipid mεtabolism. Dɛn bin sheb di mays dɛn to wan kɔntrol grup, wan ɛksɛsayz grup, wan ɛksɛsayz + AOD9604 grup, ɛn wan AOD9604 nɔmɔ tritmɛnt grup. di risalts sho se di alanine aminotransferase (ALT) lεvεl dεm na di AOD9604 nכmכ grup εn di εksεsayz + AOD9604 grup bin sכmtεm lכw pas di wan dεm na di kכntrol grup, we sho se AOD9604 gεt sכm prכtektiv ifekt pan di liva dεmεj. dis kin bi fכ AOD9604 we de rεgεl di lipid mεtabolism na di liva, we de ridyus fεt akyumyuleshכn na di liva, we de mek di hεpatik stεatosis εn inflammatory rεspכns dεm nכ de.
ifekt dεm pan di liva εnzym dεm εn saytokεratin-18 (CK18): Saytokεratin-18 na bayomak we de sho di εpatosayt apoptosis. Insay di ɛkspiriɛns, pan ɔl we di AOD9604 monotɛrapi grup nɔ bin ridyus di CK18 lɛvɛl dɛn bad bad wan, i nɔ bin prodyuz nɛgitiv ifɛkt bak. dis sho se AOD9604 kin indaykt infכmeshכn di apoptosis prכsεs fכ di liva sεl dεm bay we i de rεgεl di hεpatik lipid mεtabolism, we de protεkt di liva sεl dεm frכm damej to sכm mak. AOD9604 kin mεnten di bεlε fכ di hεpatik lipid mεtabolism bay we i de rεgεl di εksprεshכn fכ di jin dεm we riliyt to lipid sεntez, transpכt, εn dεgradashכn na di liva, we de ridyus abnכmal fεt akyumyuleshכn na di liva.
Aplikeshɔn dɛn fɔ AOD9604
(1) Pɔtɛnɛshɛl Aplikeshɔn fɔ Ɔbisiti Tritmɛnt
Advantej ɛn Prɔspɛkt: We yu kɔmpia am wit tradishɔnal mɛrɛsin dɛn we de mek pɔsin nɔ gɛt bɔku bɔku bɔdi, AOD9604 gɛt bɔku bɛnifit dɛn we i kin gɛt. I nɔ gɛt di sayd ɛfɛkt dɛn we gɛt fɔ du wit dayabitis we gɛt fɔ du wit hGH. hGH kin mek bad bad tin apin lɛk insulin rɛsistɛns ɛn ɛlevɛt blɔd glukɔs lɛvɛl we dɛn yuz am fɔ trit fat. AOD9604 de avɔyd dɛn sayd ifɛkt ya tru in yon strɔkchɔral dizayn. AOD9604 kin spεshal rεgulεt lipid mεtabolism, protεkt fεt brεkdכwn, εn inkrεs εnεji εspεndishכn, we de gi prכmis tritmεnt prכspεkt fכ pasεnshכn dεm wit simpul fεt. in mεkanism fכ akshכn involv mכltipכl lεvεl dεm, nכto כnli tru rεguleshכn fכ di β-adrenergic path bכt bak tru wan mεkanism we indipεndεnt frכm β(3)-AR, we de gi mכr kכmprεhεnsiv intavεnshכn aprכch fכ fכ tritmεnt fכ fat.
(2) Potεnshal aplikεshכn dεm fכ trit liva sik dεm
Potεnshal fכ trit non-alcoholic fatty liver disease (NAFLD): NAFLD na wan kכmכn liva sik we dεn kכl fεt we de kכmכt pasmak na di liva. insay wan maws mכdel fכ fεt liva sik, AOD9604 kin rεgεl di hεpatik lipid mεtabolism, ridyus di liva fεt kכntεnt, εn impruv di liva fכnshכn mak dεm. AOD9604 gɛt sɔm aplikeshɔn valyu fɔ di tritmɛnt fɔ NAFLD. i kin ridyus di fεt we de kכmכt na di liva bay we i de mek di fεt brok εn transpכt fεt insay di liva, we de mek di hεpatik stεatosis εn inflammatory rεspכns dεm nכ de. AOD9604 kin rεgεl כksidεtiv strεs εn inflammatory signal path dεm insay di liva, fכ protεkt di liva sεl dεm mכr frכm damej.
Dɔn
as pεptida we kכmכt frכm di C-tεrminal rijyכn fכ di hכmon gכt hכmon, di mεkanism fכ akshכn fכ AOD9604 fכ rεgεl di lipid mεtabolism involv intarakshכn wit di β-adrenergic path εn dayrekt ifekt dεm we indipεndεnt frכm β(3)-AR. tru dεn mεkanism dεm ya, AOD9604 de ridyus di bכdi wet εn di bכdi fεt fayn fayn wan, i de inkrεs di εnεji we i de spεnd, i de rεgεl di fεt כksidεshכn, εn i de impruv di hεpatik lipid mεtabolism. We i kam pan aplikeshɔn, AOD9604 gɛt impɔtant prɔmis fɔ trit fat, spɔt mɛrɛsin, ɛn liva sik.
Sos dɛn we dɛn pul
[1] Dehbashi M, Fathi M, Attarzadeh Hosseini S. R., ɛn ɔda pipul dɛn. di Efεkt כf Et Wik εndurεns Trenin, Somatropin Injεkshכn, εn In Lipolytic Fragment (AOD9604) pan Saytokeratin-18 εn Liva εnzym dεm fכ Mays indyuz Liva Dεmεj Bikɔs ɔf wan Ay-Fεt Dayt[J]. Kwataly ɔf di Ɔrayzɔn ɔf Mɛdikal Sayns, 2021,27:502-517.DOI:10.32598/hms.27.4.3513.1.
[2] Kɔks H. D., Smeal S. J., Hughes C. M., ɛn ɔda pipul dɛn. Ditekshɔn ɛn in vitro mɛtabolism fɔ AOD9604[J]. Drug Tɛstin ɛn Analysis, 2015,7(1):31-38.DOI:10.1002/dta.1715.
[3] Stier H, Vos E, Kenley D L. Sefty ɛn Tolerabiliti fɔ di Hɛksadekapɛptida AOD9604 insay Mɔtalman[J]. J ɔ rnal ov Ɛndokrinɔlɔji ɛn Mɛtabolism, 2013,3:7-15.
Di s://api.semanticscholar.org/KɔpɔsID:56559133. Di wan dɛn we de stɔdi bɔt di Baybul
[4] Witkamp R F. Kɔrɛnt ɛn Fyuchɔ Drug Target in Weyt Manejmɛnt[J]. Famasiutik Risach, 2011,28(8):1792-1818.DOI:10.1007/s11095-010-0341-1.
Prodak we de fɔ yuz fɔ risach nɔmɔ:
