Kaofela rea ??tseba hore khatello ea kelello ea nako e telele e ka lebisa letotong la mathata a bophelo bo botle ba 'mele le a kelello, a kang ho t?oenyeha, ho tepella maikutlong le maikutlo a mang a fosahetseng, hammoho le mathata a takatso ea lijo, mathata a boima ba' mele le mathata a mang a metabolism. Batho ba bangata ba tobane le khatello ea maikutlo, ba tla bont?a ho ja maikutlo (ho ja maikutlo), ke hore, ka ho ja haholo ho imolla maikutlo a mabe a bakoang ke khatello ea maikutlo. Ho ja ka maikutlo hangata ho tsamaisana le lik’hilojule tse feteletseng, e leng e ’ngoe ea mabaka a kotsi a botenya. Joale, ke mokhoa ofe oo khatello ea kelello e bakang mathata a takatso ea lijo ka eona? Kamano ke efe lipakeng tsa tryptophan metabolism le ho ja maikutlo ho bakoang ke khatello ea maikutlo? Ho rarolla mathata ana, bafuputsi ba entse letoto la liphuputso tse qaqileng.

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Tryptophan ke e 'ngoe ea li-amino acid tsa bohlokoa' meleng oa motho le selelekela sa neurotransmitter 5-hydroxytryptophan (5-HT, e tsejoang hape e le serotonin) bokong. Liphuputso tse ngata li bont?itse hore mathata a metabolism ea tryptophan a amana haufi-ufi le mafu a sa t?oaneng a kelello, a kang ho tepella maikutlong, ho t?oenyeha, schizophrenia joalo-joalo. Ka nako e ts'oanang, tryptophan le metabolite 5-HT ea eona e boetse e ameha ho laola takatso ea lijo le ho leka-lekanya matla. Kahoo, tlas'a maemo a khatello ea maikutlo a sa foleng, na metabolism ea tryptophan e fetoha? Na phetoho ee e amana le mokhoa o sa tloaelehang oa ho ja o bakoang ke khatello ea maikutlo? Ka lipotso tsena kelellong, bafuputsi ba ile ba etsa letoto la liteko tse qaqileng.

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Ntlha ea pele, bafuputsi ba ile ba sebelisa litoeba ho hlahisa mokhoa o sa foleng o bakoang ke khatello ea maikutlo (CMS). Ba ile ba kenya litoeba likhatellong tse fapaneng tse sa lebelloang, joalo ka khatello ea maikutlo, ho tsukutloa koae le libate tsa metsi a batang, ka matsatsi a 21 a latellanang ho etsisa khatello e phehellang, e fapaneng bophelong ba nnete. Liphello li bont?itse hore ka mor'a matsatsi a 21 a khatello ea kelello e sa foleng, litoeba li ile tsa bont?a ho t?oenyeha ho hoholo le boit?oaro bo kang ba ho tepella maikutlong. Tekong e bulehileng (OFT), nako ea litoeba tsa sehlopha sa CMS tse lulang sebakeng se bohareng sa lebala le bulehileng e ile ea khutsufatsoa haholo, e leng se bont?ang hore boemo ba bona ba ho t?oenyeha bo eketsehile. Tekong ea ho fanyeha mohatla (TST), nako ea ntoa ea litoeba sehlopheng sa CMS e ile ea khutsufatsoa haholo, e fana ka maikutlo a ho hloka t?epo. Ka nako e ts'oanang, lijo tsa litoeba tsa sehlopha sa CMS li ile tsa eketseha haholo, empa boima bo ile ba fokotseha haholo, ho fana ka maikutlo a hore takatso ea bona ea lijo le metabolism li ne li khathatsehile.

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Kamora moo, bafuputsi ba ile ba etsa tlhahlobo e lebisitsoeng ea metabolomic ea tsela ea metabolic ea tryptophan ho serum ea mouse. Liphello li bont?itse hore serum tryptophan content ea litoeba tsa sehlopha sa CMS e fokotsehile haholo, ha metabolites e tlaase ea 5-hydroxytryptamine (5-HT) le litaba tsa kynurenine li eketsehile haholo. Litlhahlobo tse ling li bont?itse hore polelo ea mRNA ea tph1, e leng enzyme ea bohlokoa ka har'a synthesis ea 5-hydroxytryptamine, e ne e theohile haholo ka har'a lisele tsa litoeba tsa sehlopha sa CMS, mme litaba tsa 5-HT ka har'a kolone le tsona li bonts'itse mokhoa o tlase. Sena se fana ka maikutlo a hore khatello ea kelello e sa foleng e senya homeostasis ea tryptophane-5-HT tsela ea metabolic ka har'a mala a litoeba, e leng se bakang ho se leka-lekane ha maemo a peripheral 5-HT.

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Le hoja tryptophan e ke ke ea fetisa ka ho toba mokoallo oa mali-boko, metabolite 5-HT ea eona e phetha karolo ea bohlokoa e le neurotransmitter tsamaisong ea methapo e bohareng 'me e ameha ho laola mekhoa e mengata ea 'mele e kang maikutlo, ho tseba le ho ja. Bafuputsi ba ile ba tsoela pele ho sekaseka liphetoho polelong ea li-neuropeptides tse 'maloa le li-receptor tsa 5-HT tse amehang taolong ea takatso ea lijo ho hypothalamus. Liphetho li bonts'itse hore khatello ea maikutlo e sa foleng e laetse haholo polelo ea takatso ea lijo e khothalletsang li-neuropeptides joalo ka AgRP le OX1R, ha e ntse e theola polelo ea lintho tse thibelang takatso ea lijo tse kang LEPR, MC4R le 5-HT1B. Sena se fana ka maikutlo a hore t?itiso ea tsela ea tryptophane-5-HT e ka lebisa boit?oarong bo sa tloaelehang ba ho fepa ka ho ama hypothalamic neural circuit.

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Joale, na tlatsetso ka tryptophan e ka imolla maikutlo a sa foleng a bakoang ke khatello ea maikutlo le ho se tloaelehe ha ho ja? Litekanyetso tse peli tsa tryptophan (100mg/kg le 300mg/kg) li ile tsa fuoa litoeba tsa CMS ka gavage ea letsatsi le letsatsi bakeng sa matsatsi a 21. Liphello li bont?itse hore ka mor'a matsatsi a 21 a ho kenella ka tekanyo e phahameng ea tryptophan (300mg / kg), ho t?oenyeha le boit?oaro bo kang ba ho tepella maikutlong ba litoeba tekong e bulehileng ea teko le teko ea ho emisa mohatla e ile ea ntlafatsoa haholo, 'me ho sa tloaelehang ho eketseha ha lijo le ho theola boima ba' mele ho ile ha lokisoa. Liphuputso tse ling li bont?itse hore ho kenella ka tekanyo e phahameng ea tryptophan ho ka thibela ho phahama ha maemo a takatso ea lijo a kang AgRP le OX1R ho hypothalamus e bakoang ke khatello ea kelello e sa foleng, ha e ntse e tsosolosa polelo ea takatso ea lijo e thibelang lintho tse kang LEPR, MC4R, 5-HT1B le 5-HT2C. Ke habohlokoa ho hlokomela hore le hoja tekanyo e tlaase ea tryptophan (100mg/kg) sehlopha ha ea ka ea bont?a ntlafatso e kholo ea mat?oao a boit?oaro, ho ne ho e-na le mokhoa oa ho fetoha ha hypothalamic takatso ea lijo e amanang le liphatsa tsa lefutso boemong ba molek'hule.

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Liphuputso tse ling tsa mekhoa ea limolek'hule li bont?itse hore 5-HT, ka ho tlama li-receptor tsa 5-HT1B le 5-HT2C ho hypothalamic POMC, AgRP le li-neurone tse ling, li thibela AgRP/NPY neurons tse khothalletsang takatso ea lijo, li kenya t?ebetsong li-neurons tsa POMC tse thibelang takatso ea lijo le ho khothalletsa t?ebeliso ea matla, ebe e phetha karolo ea ho laola boima ba 'mele. Sena se fana ka ts'ehetso ea bohlokoa ea limolek'hule bakeng sa ntlafatso ea phepo ea maikutlo ka tsela ea tryptophan-5-HT.

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Bafuputsi ba boetse ba sebelisitse mouse ea hypothalamic neuron cell line GT1-7 ho netefatsa ts'ebetso ea taolo ea 5-HT ho li-neuropeptides tse amanang le takatso ea lijo. Ba ile ba t?oara lisele tsa GT1-7 ka 10μM ea corticosterone (CORT) bakeng sa lihora tse 24 ho etsisa maemo a sa foleng a khatello ea kelello. Liphetho li bonts'itse hore polelo ea takatso ea lijo e khothalletsang liphatsa tsa lefutso tse joalo ka AgRP le OX1R e ne e laoloa haholo ke kalafo ea CORT, athe polelo ea takatso ea lijo e thibelang liphatsa tsa lefutso tse kang MC4R, 5-HT1B le 5-HT2C e ne e laoloa. Ka mor'a ho phekola pele ka 0.1μM 5-HT bakeng sa lihora tsa 2, polelo e sa tloaelehang ea AgRP e susumelitsoeng ke CORt le mefuta e meng ea lefutso e ka fetoloa haholo, 'me polelo ea MC4R, 5-HT1B le 5-HT2C e ka tsosolosoa. Sena se ile sa tiisa hape phello e tobileng ea taolo ea 5-HT ho li-neuron tsa hypothalamic.

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Kakaretso ea lintlha:

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Liphello tsa khatello ea kelello e sa foleng ho tryptophan metabolism homeostasis ho litoeba: Khatello e sa foleng e ile ea etsa hore maemo a serum tryptophan a fokotsehe (P

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Phello ea tryptophan takatsong ea lijo le boits'oaro bo kang ba ho tepella maikutlo bo bakoang ke khatello ea kelello e sa foleng: Tlatsetso ea tekanyo e phahameng ea tryptophan e tsosolositse boit?oaro bo sa tloaelehang ba ho ja le ho lahleheloa ke boima ba 'mele bo bakoang ke khatello ea kelello e sa foleng (P

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Liphello tsa tlatsetso ea tryptophan ho li-neuron tse fepang hypothalamic le balaoli ba takatso ea lijo litoeba tse sa foleng tsa khatello ea maikutlo: Ho silafatsa ha Immunohistochemical ho bont?itse hore polelo ea c-fos le AgRP sebakeng sa ARC sa hypothalamus sehlopheng sa khatello ea maikutlo e sa foleng e ile ea eketseha haholo, ha polelo ea LEPR e fokotsehile haholo (P

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Liphello tsa tryptophan ho 5-HT tsela ea metabolic ho hypothalamus ea litoeba tse sa foleng tsa khatello ea kelello: Serum tryptophan le maemo a 5-HT a ile a eketseha haholo ka mor'a hore tryptophan supplementation (P

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Ka kakaretso, thuto ena e senola hore khatello ea kelello e sa foleng e baka t?itiso ea marang-rang a taolo ea takatso ea lijo ea hypothalamic ka ho senya tryptophane-5-HT tsela ea metabolic, e leng eona e bakang ho ja maikutlong. Tlatsetso ea exogenous tryptophan, haholo-holo ka tekanyo e phahameng (300mg/kg), e khutlisetsa maemo a bohareng a 5-HT, e kenya t?ebetsong li-receptor tsa hypothalamic 5-HT1B le 5-HT2C, e thibela li-neurons tsa AgRP/NPY, e kenya t?ebetsong li-neurons tsa POMC, le ho ntlafatsa mathata a maikutlo a amanang le khatello ea maikutlo le boit?oaro bo sa tloaelehang ba ho ja.

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Sephetho sena sa lipatlisiso se na le bohlokoa ba bohlokoa bo sebetsang. Bophelong ba kajeno bo potlakileng, bo nang le khatello e phahameng ea maikutlo, batho ba bangata ba tobane le mathata a maikutlo a bakoang ke khatello ea maikutlo le mathata a boima ba 'mele. Liphuputso li bont?itse hore khatello ea kelello ea nako e telele e etsa hore 'mele oa tryptophan o fokotsehe, 5-hydroxytryptamine synthesis e fokotsehe, ebe e lebisa letotong la mathata a neuroendocrine, a lebisang ho tepella maikutlong, ho t?oenyeha le maikutlo a mang a fosahetseng, hammoho le hyperappetite, botenya le mathata a mang a metabolism. Phuputso ena e senola karolo e ka sehloohong ea tryptophan le metabolite ea eona ea 5-hydroxytryptophan molemong oa taolo ea khatello ea maikutlo-maikutlo, ho fana ka maikutlo a macha le mekhoa ea ho imolla khatello ea maikutlo le ho ntlafatsa mathata a maikutlo le boima ba 'mele.

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Ho latela liphuputso, bafuputsi ba fana ka litlhahiso tse ling tsa lijo ho thusa batho ho sebetsana hantle le khatello ea maikutlo. Pele ho tsohle, tlatsetso e nepahetseng ea lijo tse ruileng tsa tryptophan lijong tsa letsatsi le letsatsi, joalo ka mahe, chisi, linate, libanana, oats, joalo-joalo, li ka thusa ho ntlafatsa boemo ba tryptophan 'meleng, ho khothaletsa motsoako oa 5-hydroxytryptophan, ka hona ho ntlafatsa boemo ba maikutlo le ho thibela khatello ea maikutlo ho ja. Leha ho le joalo, hoa lokela ho hlokomeloa hore tryptophan lijong ha e kenelle ka 100% le ho sebelisoa. Ka nako e ts'oanang, tlatsetso e kholo ea nako e telele ea tryptophan (joalo ka ho feta 500mg / kg) e ka baka t?enyo ea liphio. Ka hona, ho leka-lekana ha lijo tsa letsatsi le letsatsi, tlatsetso e itekanetseng ea tryptophan e ka ba, u se ke ua buella t?ebeliso e feteletseng ea li-tryptophan.

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Ho feta moo, boikoetliso bo itekanetseng bo kang ho matha, ho sesa, yoga, joalo-joalo, le hona ho ka thusa ho eketsa boemo ba tryptophan le serotonin synthesis 'meleng, ho imolla khatello ea maikutlo le ho ntlafatsa maikutlo. Ho robala ka ho lekaneng, ho ba le boikutlo bo nepahetseng le ba ho ba le t?epo, le ho ithuta ho nt?a maikutlo ka tsela e utloahalang, kaofela ke litsela tse molemo tsa ho sebetsana le khatello ea maikutlo. Ha u tobane le mathata a tebileng a maikutlo a kang ho tepella maikutlong le ho t?oenyeha, hoa hlokahala ho batla phekolo ea kelello ea setsebi ka nako.

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Qetellong, thuto ena e senola mokhoa oa ho ja maikutlong o bakoang ke khatello ea kelello e sa foleng ho latela pono ea tryptophan metabolism, 'me e fana ka pono e ncha ea ho imolla khatello ea kelello, ho ntlafatsa mathata a maikutlo le mathata a boima ba' mele. Leha lithuto tse ling tsa baahi li hlokahala ho ntlafatsa litekanyetso le nako ea tlatsetso ea tryptophan lijong, liphetho tsa phuputso ena li re file mehopolo e mecha ea ho khothaletsa bophelo bo botle ba 'mele le kelello ka taolo ea lijo. Re lumela hore ka ho ja lijo tse leka-lekaneng, boikoetliso bo itekanetseng, boroko bo botle le ho sebetsana ka katleho le maikutlo a matle, re ka khona ho tobana le khatello ea bophelo re khobile mat?oafo le ho amohela bokamoso bo molemonyana.