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▎ Gịnị bụ AOD 9604?
AOD 9604 bụ peptide sịntetik nke sitere na C-terminal (amino acids na ọnọdụ 176-191) nke hormone na-eto mmadụ (HGH), nke phenylalanine na N-terminal na-eji tyrosine dochie ya. Emebere ya na mbụ maka ọgwụgwọ oke ibu ma mee ya ka ọ dị ka ihe ọkụkụ na-ere ọkụ nke HGH, ma na-enweghị mmetụta uto muscle ma ọ bụ mmetụta ndị ọzọ metụtara HGH.
Ọrụ bụ isi nke AOD 9604 bụ ịkpali lipolysis, na-enyere aka ịkụda ma mebie abụba, ebe ọ na-egbochi lipogenesis iji gbochie abụba sitere n'ime nri ka ọ ghọọ abụba anụ ahụ. Ọ dị irè karịa Aod 9401 bu ụzọ ya na-akpali akpali lipolysis na mgbochi lipogenesis. Tụkwasị na nke ahụ, AOD 9604 na-egosipụtakwa mmetụta dị mma na ọkpụkpụ ọkpụkpụ ma nwee ike inye aka na ọgwụgwọ nke ọrịa ọkpụkpụ dịka ọkpụkpụ ọkpụkpụ.
Ihe dị mkpa nke AOD 9604 dị na ịnye nhọrọ ọhụrụ maka ọgwụgwọ oke ibu. Ọ nwere ike inyere ndị mmadụ aka ịkụ abụba ma felata nke ọma karị, ebe ị na-ezere mmetụta ndị nwere ike ime nke HGH. Ọzọkwa, itinye ya n'ọrụ na metabolism ọkpụkpụ na-agbakwunyekwa uru ahụike ọzọ na ya.
Uru nke AOD 9604 gụnyere mmetụta ya ezubere iche na metabolism abụba, na-enweghị emetụta shuga ọbara ma ọ bụ uto.
▎ AOD 9604 Ọdịdị
Isi mmalite: PubChem |
Usoro: SALLRSIPAPAGASRLLLLTGEIDLP Ụdị mkpụrụ ndụ: C 78H 123N 23O 23S2 Arọ molekụla: 1815.1g/mol Nọmba CAS: 221231-10-3 PubChem CID: 71300630 |
▎ AOD 9604 Nchọpụta
Kedu ihe ndabere nyocha nke AOD 9604?
AOD 9604 bụ peptide nke mejupụtara iberibe C-terminal nke hormone uto mmadụ (hGH), kpọmkwem usoro amino acid 177 - 191, yana mgbakwunye tyrosine ọzọ na N-terminus nke peptide.
Mmekọrịta dị n'etiti AOD 9604, hormone na-eto eto, na ọgwụgwọ oke ibu bụ ndị a. Ọ bụ ezie na homonụ na-eto mmadụ (hGH) nwere ikike ịgwọ oke ibu, nsogbu nchekwa na-egbochi iji ya ogologo oge. Dị ka akụkụ C-terminal nke hGH, AOD 9604 na-ewere na ọ nwere ike ịrụ ọrụ n'ịgwọ oke ibu na-enweghị ịkpata mmetụta ọjọọ nke hGH. Nnyocha achọpụtala na ma hGH na AOD 9604 nwere ike ime ka ọ dị arọ ma mee ka mmetụta nke lipolytic dịkwuo ogologo mgbe ọgwụgwọ ogologo oge na ụmụ oke. Otu usoro nwere ike ime bụ site na mmekọrịta ya na ụzọ β-adrenergic, karịsịa na beta (3) -adrenergic receptors (β3-AR) [1] .
Ma hGH na AOD 9604 nwere ike ibelata ibu ahụ na abụba anụ ahụ nke oke oke ibu, yana nsonaazụ a metụtara mmụba ọkwa nke β3-AR RNA, onye na-anabata lipolytic bụ isi na adipocytes. N'ụzọ dị mkpa, ma hGH na AOD 9604 nwere ike ịbawanye ọkwa β3-AR RNA na-ebelata na oke oke oke na ọkwa yiri nke ahụ na ụmụ oke na-adabere na ya [1] .
Otú ọ dị, na ụmụ oke β3-AR knockout, iji hGH na AOD 9604 mee ogologo oge emeghị ka mgbanwe dị arọ na ụbara lipolysis hụrụ na ụmụ oke nchịkwa ụdị anụ ọhịa. Mana n'ime nnwale siri ike, AOD 9604 nwere ike ịbawanye oriri ike yana oxidation abụba na ụmụ oke β3-AR knockout [1].
Ọgwụgwọ nke ọrịa ogbu na nkwonkwo: Intra-articular injections nke AOD 9604 egosila ụfọdụ ọgwụgwọ ọgwụgwọ na ụdị oke bekee nke ọrịa ogbu na nkwonkwo. Nchoputa nke Kwon Dong Rak na Park Gi Young na-egosi na ultrasound-eduzi intra-articular injections nke AOD 9604 na-eme ka cartilage regeneration, na ngwakọta nke AOD 9604 na hyaluronic acid (HA) dị irè karịa iji HA ma ọ bụ AOD 9604 naanị [2] .
Akwupụtala AOD 9604 ka ọ na-eṅomi njirimara lipolytic nke hormone uto na-enweghị mmetụta dị n'akụkụ nke ịkpata ọrịa shuga. Ya mere, enwere ike iji ya dị ka ọgwụ na-eme ka ọ rụọ ọrụ nke ọma yana World Anti-doping Agency (WADA) machibidoro ya [3].
Nchọpụta nyocha nke AOD 9604 sitere na esemokwu dị n'etiti ikike nke hormone uto mmadụ n'ịgwọ oke ibu na nsogbu nchekwa ya. N'otu oge ahụ, na mmụba nke ọrịa metabolic, ọrụ ọ nwere n'ịkwalite ahụike nke metabolic na nchekwa ya aghọwo ihe nyocha.
Kedu njirimara na uru nke usoro nke AOD 9604 na mbelata ibu na usoro metabolic?
Nke mbụ, n'ihe gbasara lipolysis, AOD 9604 na-eme ka mmetụta nke lipolysis dịkwuo elu site n'ịgbalite ụzọ β3-adrenergic receptor (β3-AR) nke adipocytes. Nke a ịgbalite na-enyere adipocytes aka n'ụzọ dị irè gbarie triglycerides echekwara n'ime free ọdụdụ asịd na glycerol, si otú na-akwalite decomposition na itinye n'ọrụ nke abụba na-enye ike maka ahụ. Ọ bụghị naanị na usoro a na-enyere aka ibelata mkpokọta abụba anụ ahụ kamakwa ọ na-eme ka nkesa abụba dịkwuo mma, na-ebelata oke abụba visceral, wee si otú a na-ebelata ohere nke ọrịa dị iche iche metụtara oke ibu, dị ka ọrịa obi na akwara ozi na ụdị ọrịa shuga 2.
Nke abuo, AOD 9604 na-arụkwa ọrụ nke ọma na igbochi lipogenesis. Ọ nwere ike igbochi abụba sitere n'ime nri ka ọ bụrụ abụba anụ ahụ site n'ịhazi okwu mkpụrụ ndụ ihe nketa metụtara lipogenesis. Kpọmkwem, AOD 9604 nwere ike igbochi ọrụ nke enzymes lipogenic isi dị ka fatty acid synthase, si otú ahụ belata njikọ na nchekwa nke fatty acids. Mmetụta mgbochi a na-enyere aka belata mmụba na ọdịiche nke adipocytes ma gbochie mgbasawanye nke anụ ahụ adipose, si otú a na-enweta mmetụta nke ọnwụ. N'otu oge ahụ, nke a inhibitory mmetụta nwekwara ike na-enyere aka ịnọgide na-enwe itule nke ahụ abụba metabolism na-ezere metabolic ọrịa kpatara oke abụba mkpokọta.
N'ihe gbasara usoro metabolic, ọrụ AOD 9604 dị mgbagwoju anya na nke zuru oke. Ọ nwere ike ịgbanwe metabolism ike nke anụ ahụ site na metabolism glucose ka ọ bụrụ abụba abụba, ngbanwe a dịkwa oke mkpa maka mbelata ibu na melite ahụike metabolic. Site n'ịba ụba oxidative decomposition nke fatty acids, AOD 9604 na-enyekwu ume ike maka ahụ ma na-ebelata ịdabere na glucose metabolism. Usoro metabolic a abụghị naanị na-enyere aka ịbawanye ọnụego metabolic basal, na-eme ka ahụ na-erikwu ume na izu ike, mana ọ na-eme ka mmetụta insulin dịkwuo mma, na-akwalite nnabata na itinye n'ọrụ nke glucose, ma si otú a na-ejigide nkwụsi ike nke ọkwa shuga dị n'ọbara. Na mgbakwunye, mmetụta usoro metabolic a na-enyere aka belata ntinye abụba na akụkụ ahụ dị ka imeju, na-egbochi ma melite ọrịa metabolic dị ka imeju abụba.
N'ikpeazụ, AOD 9604 nwere uru pụrụ iche na ibelata nguzogide insulin. Tụnyere homonụ uto zuru oke, AOD 9604 na-ewepụ mmetụta ndị nwere ike ibute nguzogide insulin na mmụba shuga ọbara. Ọganihu a na-eme ka AOD 9604 dị nchebe n'oge usoro ọgwụgwọ na ọ gaghị enwe mmetụta ọjọọ na ọkwa shuga dị n'ọbara. Nke a nwere mkpa ụlọ ọgwụ dị mkpa maka ndị ọrịa buru ibu, ọkachasị ndị nwere insulin na-eguzogide ma ọ bụ shuga ọbara na-adịghị mma. AOD 9604 nwere ike ọ bụghị nanị na-enyere ha aka ifelata kamakwa imeziwanye mmetụta insulin, belata ihe ize ndụ nke ịmalite ịmalite ọrịa shuga 2, ma melite ọkwa ahụike metabolic n'ozuzu ya.
Na mmechi, AOD 9604 na-arụ ọrụ ya na oke ibu na usoro metabolic site na ọtụtụ usoro nke ime ihe, na-enye nhọrọ ọhụrụ na olileanya maka ọgwụgwọ oke ibu na ọrịa metabolic.

Mmetụta nke AOD9604 na mkpokọta oke ahụ nke oke oke Zucker (fa/fa). A na-enye anụmanụ ule (p) kwa ụbọchị ọgwụ ọnụ nke 500 Ìg nke AOD9604 maka ịdị arọ ahụ maka ụbọchị iri abụọ, na anụmanụ ndị na-achịkwa (P) na-anata nha nha saline kwa ụbọchị n'otu aka ahụ. Nsonaazụ bụ pụtara B SEM nke anụmanụ 8. E ji akara nrịbama gosi ndịiche dị mkpa.
Isi mmalite: PubMed [5]
Kedu njikọ a kapịrị ọnụ nke AOD 9604 na-emetụta metabolism abụba?
Mmekọrịta na ụzọ β-adrenergic: Nnyocha egosiwo na hGH na mpempe akwụkwọ lipolytic AOD 9604 na-emepụta site na C-terminal ya nwere ike ime ka ọ dị arọ ma mee ka mmetụta nke lipolytic dịkwuo elu mgbe ọgwụgwọ ogologo oge na ụmụ oke [4] . Otu usoro enwere ike bụ site na mmekọrịta ya na ụzọ β-adrenergic, karịsịa na β₃-adrenergic receptor (β₃-AR). N'ime ụmụ oke buru ibu, hGH na AOD 9604 nwere ike ịbawanye ọkwa ngosipụta nke β₃-AR RNA ma nwee ike ịbawanye ọkwa β₃-AR RNA akpọchiri na ụmụ oke buru ibu na ọkwa yiri nke ahụ na ụmụ oke. Otú ọ dị, ọgwụgwọ ogologo oge nke ụmụ oke β₃-AR knockout nwere hGH na AOD 9604 emeghị ka mgbanwe dị arọ na ụbara lipolysis hụrụ na ụmụ oke nchịkwa anụ ọhịa. Mana n'ime nnwale siri ike, AOD 9604 nwere ike ịbawanye oriri ike yana oxidation abụba na ụmụ oke β₃-AR knockout. Nke a na-egosi na mmetụta lipolytic nke hGH na AOD 9604 abụghị onye ogbugbo ozugbo site na β₃-AR, n'agbanyeghị na ha abụọ nwere ike ịbawanye okwu nke β₃-AR, nke nwere ike mechaa nyere aka kwalite nghọta lipolytic.
Ịba ụba oxidation abụba na lipolysis na-akpali akpali: Na oke ibu (ob / ob) na lean C57BL / 6J ụmụ oke, mmetụta na-adịghị ala ala nke hormone na-eto eto mmadụ (hGH) na AOD 9604 (akụkụ C-terminal nke hGH) nwere ike ịhụ na ịdị arọ ahụ, nguzozi ike, na ọnụego oxidation substrate. Ma hGH na AOD 9604 na-ebelata oke ibu nke oke oke ibu, nke metụtara ụbara oxidation abụba n'ime ahụ yana mmụba glycerol plasma (ihe ngosi nke lipolysis). N'adịghị ka hGH, AOD 9604 anaghị akpata hyperglycemia ma ọ bụ belata mmepụta insulin. AOD 9604 adịghị mpi na onye na-anabata hGH ma ọ dịghị eme ka cell gbasaa dị ka hGH. Nke a na-akwadokwa echiche nke hGH dị ka prohormone, na-egosi na iberibe hGH nwere ike ime n'ụzọ dị iche na ụzọ mkpali hGH omenala [4] .
Gịnị bụ mmetụta AOD 9604 na imeju?
Mmetụta nke AOD 9604 na imeju na-egosipụtakarị na mmetụta nchịkwa ya na metabolism abụba. Dị ka polypeptide sịntetik nke na-eṅomi ngalaba ọrụ lipolytic nke hormone uto mmadụ (hGH), AOD 9604 nwere ike ịkwalite lipolysis, gbochie lipogenesis, ma gbanwee ike nke anụ ahụ site na glucose metabolism na abụba metabolism. Usoro a na-eme ihe na-enyere aka belata mkpokọta abụba n'ime imeju, si otú a na-enye nchebe ụfọdụ na imeju. Maka ọrịa metabolic dị ka imeju abụba abụba, oke ibu na usoro iwu metabolic nke AOD 9604 nwere ike inye aka melite ọkwa metabolism abụba nke imeju, belata ibu dị na imeju, wee si otú a kwalite ọrụ imeju. Agbanyeghị, enwere ọmụmụ ihe ole na ole ugbu a gbasara mmetụta AOD 9604 na imeju. The n'elu mmetụta na-tumadi speculated dabeere na ya mmetụta na abụba metabolism, na ndị ọzọ na nkà mmụta sayensị nnyocha ka dị mkpa iji nyochaa kpọmkwem imeju nchedo mmetụta na usoro nke edinam.
Kedu ihe AOD 9604 pụtara?
AOD 9604 bụ polypeptide sịntetik nke na-eṅomi ngalaba ọrụ lipolytic nke hormone uto mmadụ (HGH), yana uru ngwa ahụike ya bara uru. N'ịgwọ oke ibu na ọrịa metabolic, AOD 9604 nwere ike ịkwalite lipolysis nke ọma, na-egbochi lipogenesis, na ịhazi usoro metabolic nke anụ ahụ, na-enyere ndị ọrịa buru ibu aka ifelata, melite ihe mejupụtara ahụ, ma nwee uru ngwa ngwa na ọgwụgwọ nke ọrịa metabolic dị ka imeju abụba. E jiri ya tụnyere hormone na-eto eto zuru oke, ọ na-ewepụ mmetụta ndị nwere ike ịkpata nguzogide insulin na ụbara shuga dị n'ọbara, ya mere ọ dị nchebe n'oge usoro ọgwụgwọ ma dị mma maka ọtụtụ ndị ọrịa.
AOD 9604 nwere ihe dị mkpa na ngalaba nyocha na mmepe ọgwụ. Dị ka a arọ ọnwụ ọgwụ na a pụrụ iche usoro nke edinam, ọ na-enye a ọhụrụ nhọrọ maka ọgwụgwọ nke oke ibu, na-egosiputa ikike nke polypeptide ọgwụ na-emeso metabolic ọrịa, na-enye ọhụrụ echiche na nnyocha ntụziaka maka ụdi mmepe nke ọzọ mma na irè arọ ọnwụ ọgwụ. Tụkwasị na nke ahụ, njikọ na nyocha nke AOD 9604 akwalitewo mmepe nke ubi nke ọgwụ polypeptide, kwadoro na ọ ga-ekwe omume nke ọgwụ polypeptide na-eṅomi na ịchịkwa ọrụ physiological kpọmkwem n'ime ahụ, ma nye ahụmahụ bara uru maka nhazi, nhazi, na njikarịcha nke ọgwụ polypeptide.
N'ịkwalite ibi ndụ dị mma, AOD 9604 nwere ike iji dị ka ụzọ enyemaka iji nyere ndị mmadụ aka ịchịkwa ibu ha ma nọgide na-enwe ahụike. Oke ibu bụ nsogbu siri ike na ọha mmadụ nke oge a, yana mmetụta mbelata ibu ya nwere ike inye nkwado ndị ọzọ maka ndị na-esiri ike ifelata site na nri dị mfe na mmega ahụ. N'otu oge ahụ, site n'ịchịkwa abụba metabolism, ọ na-enyere aka melite ọnọdụ ahụ ike nke metabolic nke anụ ahụ, belata ọkwa lipid ọbara, belata ntinye nke abụba n'ime arịa ọbara, belata ihe ize ndụ nke ọrịa ndị metụtara metabolic dị ka ọrịa obi, ma melite ogo ndụ.
AOD 9604 na-arụkwa ọrụ dị mkpa n'ịkwalite nchọpụta bụ isi. Nchọpụta ya na-enyere aka ịchọpụta usoro nke homonụ na-eto eto nke ukwuu, ọkachasị ọrụ ya na ụzọ akara na nhazi nke metabolism abụba. Site na nyocha nke AOD 9604, ndị ọkà mmụta sayensị nwere ike ịghọta nke ọma ka hormone na-eto eto si arụ ọrụ physiological site na mmekọrịta dị n'etiti ngalaba kpọmkwem na ndị na-anabata ya, na otú ọrụ ndị a si agbanwe n'okpuru ọnọdụ physiological na pathological dị iche iche. Na mgbakwunye, AOD 9604 nwere ike iji dị ka ngwá ọrụ nyocha maka nyocha metụtara abụba abụba, na-enyere ndị ọkà mmụta sayensị aka ịmụ usoro nke ire ere abụba, ọgbọ, na ntụgharị mkpụrụ ndụ cell, na-ekpughe usoro molekụla na netwọkụ nchịkwa nke abụba metabolism, na-enye ihe ndabere usoro maka mmepe nke ụzọ ọgwụgwọ na ọgwụ maka metabolism abụba na-adịghị mma.
Onye ode akwụkwọ akụkọ
Heffernan, MA nwere njikọ na Mahadum Limerick ma na-arụsi ọrụ ike n'ọtụtụ ọzụzụ agụmakwụkwọ. Ndị a gụnyere Endocrinology & Metabolism, ebe nyocha nwere ike ilekwasị anya na ọrụ homonụ na usoro metabolic n'ime ahụ. Na Science Polymer, ọrụ ha nwere ike ịgụnye ọmụmụ ihe polymer, njikọ ha, akụrụngwa na ngwa. Physiology ga-ekpuchi ọrụ na usoro nke ihe dị ndụ, ebe Nutrition & Dietetics metụtara sayensị nke nri, nri nri, na omume nri.
Banyere Onye dere ya
Ihe niile a kpọtụrụ aha n'elu bụ Cocer Peptides na-enyocha, dezie ma chịkọta ya.
Onye ode akwụkwọ akụkọ sayensị
Nnyocha nke Heffernan nwere ike nyochaa njikọ nke mpaghara ndị a, dị ka ịmepụta usoro nnyefe ọgwụ na-adabere na polymer maka nsogbu metabolic ma ọ bụ na-amụ mmetụta physiological nke mmemme oriri na-edozi ahụ site na iji usoro sayensị ihe dị elu. Ọrụ ha na-enye aka na nghọta miri emi nke usoro ndu na mmepe nke ngwọta ọhụrụ na nlekọta ahụike na sayensị ihe onwunwe. Heffernan, MA ka edepụtara na ntụaka nke ntụaka [4].
▎ Okwu ndị dị mkpa
[1] Heffernan M, Summers RJ, Thorburn A, et al. Mmetụta nke GH mmadụ na iberibe lipolytic ya (AOD9604) na metabolism lipid na-eso ọgwụgwọ na-adịghị ala ala na oke oke na β3-AR kụpụ ụmụ oke [J]. Endocrinology, 2001,142(12):5182-5189.DOI:10.1210/en.142.12.5182.
[2] Kwon DR, Park GY. Mmetụta nke Intra-articular Injection nke AOD9604 na ma ọ bụ na-enweghị Hyaluronic Acid na Rabbit Osteoarthritis Model[J]. Akụkọ banyere Clinical na Laboratory Science, 2015,45 (4): 426-432. http://www.annclinlabsci.org/content/45/4/426.long
[3] Cox HD, Smeal SJ, Hughes CM, et al. Nchọpụta na in vitro metabolism nke AOD9604[J]. Nyocha na nyocha ọgwụ, 2015,7 (1): 31-38.DOI: 10.1002 / dta.1715.
[4] Heffernan MA, Thorburn AW, Fam B, et al. Mmụba nke abụba oxidation na mbelata ibu na ụmụ oke buru ibu kpatara ọgwụgwọ na-adịghị ala ala na homonụ uto mmadụ ma ọ bụ iberibe C-terminal gbanwetụrụ[J]. Akwụkwọ akụkọ International nke oke ibu, 2001,25 (10): 1442-1449.DOI: 10.1038/sj.ijo.0801740.
[5] Ng FM, Sun J, Sharma L, et al. Ọmụmụ Metabolic nke ngalaba Lipolytic Synthetic (AOD9604) nke Hormone Growth mmadụ[J]. Nnyocha Hormone na Ọgwụ ụmụaka, 2001,53:274-278. DOI: 10.1159/000053183
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.