Tonsefe tikudziwa kuti kupsinjika kwa nthawi yayitali kumatha kubweretsa mavuto ambiri amthupi ndi m'maganizo, monga nkhawa, kupsinjika maganizo ndi malingaliro ena oipa, komanso kusokonezeka kwa chilakolako, kulemera kwa thupi ndi mavuto ena a metabolic. Anthu ambiri poyang'anizana ndi kupsinjika maganizo, adzawonetsa kudya kwamaganizo (kudya maganizo), ndiko kuti, kudya kwambiri kuti athetse maganizo oipa omwe amayamba chifukwa cha kupsinjika maganizo. Kudya mokhudza mtima nthawi zambiri kumatsagana ndi zopatsa mphamvu zambiri, zomwe ndi chimodzi mwazomwe zimayambitsa kunenepa kwambiri. Ndiye, ndi njira yanji yomwe kupsinjika kumayambitsa vuto la njala? Kodi pali ubale wotani pakati pa tryptophan metabolism ndi kupsinjika komwe kumadzetsa nkhawa? Pofuna kuthetsa mavutowa, ofufuza afufuza mwatsatanetsatane.

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Tryptophan ndi imodzi mwama amino acid ofunikira m'thupi la munthu komanso kalambulabwalo wa neurotransmitter 5-hydroxytryptophan (5-HT, yomwe imadziwikanso kuti serotonin) mu ubongo. Kafukufuku wambiri wasonyeza kuti matenda a tryptophan metabolism amagwirizana kwambiri ndi matenda osiyanasiyana a maganizo, monga kuvutika maganizo, nkhawa, schizophrenia ndi zina zotero. Panthawi imodzimodziyo, tryptophan ndi metabolite 5-HT yake imakhudzidwanso ndi kayendetsedwe ka chilakolako ndi mphamvu. Chifukwa chake, pansi pazovuta kwambiri, kodi tryptophan metabolism imasintha? Kodi kusinthaku kukugwirizana ndi kudya movutikira? Poganizira mafunso awa, ochita kafukufukuwo adayesa mwatsatanetsatane.

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Choyamba, ochita kafukufukuwa adagwiritsa ntchito mbewa kuti apange chitsanzo chodyera cham'maganizo chokhazikika (CMS). Anaika mbewazo ku zovuta zosiyanasiyana zosayembekezereka, monga kupsinjika m'ndende, kugwedezeka kwa khola, ndi kusamba kwa madzi ozizira, kwa masiku 21 otsatizana kuti ayese kupanikizika kosalekeza, kosiyanasiyana m'moyo weniweni. Zotsatira zake zidawonetsa kuti patatha masiku 21 akupsinjika kwakanthawi, mbewa zidawonetsa nkhawa yayikulu komanso kukhumudwa ngati khalidwe. M'mayesero otseguka (OFT), nthawi ya mbewa za gulu la CMS zomwe zimakhala pakatikati pa malo otseguka zinafupikitsidwa kwambiri, kusonyeza kuti nkhawa yawo yawonjezeka. Mukuyesera kupachika mchira (TST), nthawi yolimbana ndi mbewa mu gulu la CMS idafupikitsidwa kwambiri, kutanthauza kuwonjezereka kwakusowa chiyembekezo. Panthawi imodzimodziyo, kudya kwa mbewa m'gulu la CMS kunakula kwambiri, koma kulemera kunachepa kwambiri, kutanthauza kuti chilakolako chawo ndi metabolism zinasokonezeka.

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Pambuyo pake, ofufuzawo adachita kuwunika kwa metabolomic kwa tryptophan metabolic pathway mu seramu ya mbewa. Zotsatira zinawonetsa kuti seramu tryptophan zomwe zili mu mbewa za gulu la CMS zidachepa kwambiri, pomwe metabolites yakumunsi ya 5-hydroxytryptamine (5-HT) ndi kynurenine zomwe zili mkati zidawonjezeka kwambiri. Kusanthula kwina kunawonetsa kuti mawu a mRNA a tph1, enzyme yofunikira pakuphatikizika kwa 5-hydroxytryptamine, anali otsika kwambiri m'matumbo a mbewa mu gulu la CMS, ndipo zomwe zili mu 5-HT mu colon zidawonetsanso kutsika. Izi zikuwonetsa kuti kupsinjika kwakanthawi kumasokoneza homeostasis ya tryptophane-5-HT kagayidwe kachakudya m'matumbo a mbewa, zomwe zimapangitsa kuti pakhale kusalinganika kwa milingo ya 5-HT.

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Ngakhale tryptophan sangadutse mwachindunji chotchinga chamagazi-muubongo, metabolite 5-HT yake imagwira ntchito yofunika kwambiri ngati neurotransmitter m'katikati mwa mitsempha yapakati ndipo imakhudzidwa pakuwongolera njira zambiri zathupi monga kukhumudwa, kuzindikira komanso kudya. Ofufuzawo adasanthulanso kusintha kwamafotokozedwe a ma neuropeptides angapo ndi ma 5-HT receptors omwe amakhudzidwa ndi kuwongolera chilakolako mu hypothalamus. Zotsatira zake zidawonetsa kuti kupsinjika kwanthawi yayitali kumawongolera kwambiri mawu a chilakolako cholimbikitsa ma neuropeptides monga AgRP ndi OX1R, pomwe adachepetsa mawu azinthu zoletsa kudya monga LEPR, MC4R ndi 5-HT1B. Izi zikusonyeza kuti kusokonezeka kwa tryptophane-5-HT njira kungayambitse khalidwe lachilendo la kudya mwa kusokoneza hypothalamic neural circuit.

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Ndiye, kodi kuphatikizika ndi tryptophan kumachepetsa kupsinjika kwakanthawi koyambitsa kupsinjika komanso kusadya bwino? Mlingo iwiri ya tryptophan (100mg/kg ndi 300mg/kg) idaperekedwa kwa mbewa za CMS ndi gavage tsiku lililonse kwa masiku 21. Zotsatirazo zinasonyeza kuti pambuyo pa masiku a 21 akulowerera ndi mlingo waukulu wa tryptophan (300mg / kg), khalidwe lodetsa nkhawa ndi kuvutika maganizo kwa mbewa poyesa kutchire ndi kuyesa kuyimitsidwa kwa mchira kunasinthidwa kwambiri, ndipo kuwonjezereka kwachilendo kwa zakudya ndi kuchepa kwa thupi kunakonzedwa bwino. Kafukufuku wina wasonyeza kuti kulowetsedwa kwa tryptophan kwapamwamba kungathe kulepheretsa kukhazikitsidwa kwa chilakolako cholimbikitsa zinthu monga AgRP ndi OX1R mu hypothalamus chifukwa cha kupsyinjika kosatha, ndikubwezeretsanso mawu a chilakolako choletsa zinthu monga LEPR, MC4R, 5-HT1B ndi 5-HT2C. Ndizofunikira kudziwa kuti ngakhale kuti gulu lochepa la tryptophan (100mg/kg) silinawonetse kusintha kwakukulu pazizindikiro zamakhalidwe, panali chizolowezi chosintha mu hypothalamic chilakolako chokhudzana ndi jini pamlingo wa maselo.

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Kafukufuku winanso wamakina a maselo awonetsa kuti 5-HT, pomanga 5-HT1B ndi 5-HT2C zolandilira pa hypothalamic POMC, AgRP ndi ma neuroni ena, amalepheretsa ma AgRP/NPY neurons omwe amalimbikitsa chilakolako, kuyambitsa ma POMC neurons omwe amalepheretsa kulakalaka komanso kulimbikitsa kugwiritsa ntchito mphamvu, ndiyeno amatenga gawo pakuwongolera kulemera. Izi zimapereka chithandizo chofunikira cha maselo kuti apititse patsogolo kudyetsa maganizo ndi tryptophan-5-HT njira.

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Ofufuzawo adagwiritsanso ntchito mbewa ya hypothalamic neuron cell line GT1-7 kuti atsimikizire kuwongolera kwa 5-HT pama neuropeptides okhudzana ndi chilakolako. Adachitira ma cell a GT1-7 ndi 10μM ya corticosterone (CORT) kwa maola 24 kuti ayese kupsinjika kwakanthawi. Zotsatira zake zidawonetsa kuti kuwonetsetsa kwachilakolako cholimbikitsa majini monga AgRP ndi OX1R kunali koyendetsedwa kwambiri ndi chithandizo cha CORT, pomwe kufotokozera kwachilakolako choletsa majini monga MC4R, 5-HT1B ndi 5-HT2C kunali kocheperako. Pambuyo pochita bwino ndi 0.1μM 5-HT kwa maola 2, mawonekedwe achilendo a CORt-induced AgRP ndi majini ena akhoza kusinthidwa kwambiri, ndipo mawu a MC4R, 5-HT1B ndi 5-HT2C akhoza kubwezeretsedwa. Izi zinatsimikiziranso kuwongolera kwachindunji kwa 5-HT pa hypothalamic neurons.

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Chidule cha data:

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Zotsatira za kupsinjika kwanthawi yayitali pa tryptophan metabolism homeostasis mu mbewa: Kupsinjika kwanthawi yayitali kunapangitsa kuti seramu tryptophan ikhale yochepa (P

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Zotsatira za tryptophan pakufuna kudya komanso kupsinjika maganizo komwe kumabwera chifukwa cha kupsinjika maganizo: Mlingo wapamwamba wa tryptophan supplementation unabwezeretsa khalidwe losazolowereka la kudya komanso kuchepa thupi chifukwa cha kupsinjika maganizo kosatha (P

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Zotsatira za tryptophan supplementation pa hypothalamic kudyetsa neurons ndi owongolera chilakolako mu mbewa zosautsa: Kudetsa kwa Immunohistochemical kunawonetsa kuti kufotokozera kwa c-fos ndi AgRP m'chigawo cha ARC cha hypothalamus mu gulu losautsa kwambiri kunawonjezeka kwambiri, pamene mawu a LEPR adachepa kwambiri (P

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Zotsatira za tryptophan pa 5-HT metabolic pathway mu hypothalamus of chronic stress mbewa: Serum tryptophan ndi 5-HT milingo inawonjezeka kwambiri pambuyo pa tryptophan supplementation (P

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Ponseponse, kafukufukuyu akuwonetsa kuti kupsinjika kwanthawi yayitali kumayambitsa kusokonezeka kwa njira yoyendetsera chilakolako cha hypothalamic posokoneza njira ya tryptophane-5-HT, yomwe imayambitsa kudya kwamalingaliro. Kuonjezera kwa tryptophan yachilendo, makamaka mu mlingo waukulu (300mg / kg), kubwezeretsa misinkhu yapakati ya 5-HT, kumayambitsa hypothalamic 5-HT1B ndi 5-HT2C zolandilira, kumalepheretsa AgRP/NPY neurons, kuyambitsa ma POMC neurons, ndikuwongolera kusokonezeka kwamalingaliro okhudzana ndi kupsinjika ndi khalidwe losadya.

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Zotsatira za kafukufukuyu zili ndi tanthauzo lofunikira. M'moyo wamasiku ano wothamanga, wopsinjika kwambiri, anthu ambiri amayang'anizana ndi zovuta zamalingaliro zomwe zimadzetsa nkhawa komanso kupsinjika kwa thupi. Kafukufuku wasonyeza kuti kupsinjika kwa nthawi yayitali kumapangitsa kuti tryptophan ya thupi ikhale yochepa, 5-hydroxytryptamine kaphatikizidwe kameneka kamachepetsa, ndiyeno kumayambitsa mndandanda wa matenda a neuroendocrine, zomwe zimayambitsa kuvutika maganizo, nkhawa ndi maganizo ena oipa, komanso hyperappetite, kunenepa kwambiri ndi mavuto ena a metabolic. Kafukufukuyu akuwonetsa gawo lalikulu la tryptophan ndi metabolite yake 5-hydroxytryptophan mu njira yoyendetsera kupsinjika-emotion-appetite regulation, kupereka malingaliro atsopano ndi njira zochepetsera kupsinjika ndikuwongolera kusokonezeka kwamalingaliro ndi zovuta zolemera.

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Malingana ndi zomwe zapeza, ochita kafukufuku amapereka malangizo a zakudya kuti athandize anthu kuthana ndi nkhawa. Choyamba, chowonjezera choyenera cha tryptophan wolemera zakudya mu zakudya tsiku ndi tsiku, monga mazira, tchizi, mtedza, nthochi, oats, etc., zingathandize kusintha mlingo wa tryptophan mu thupi, kulimbikitsa synthesis wa 5-hydroxytryptophan, potero kuwongolera maganizo boma ndi kuletsa nkhawa kudya. Komabe, ziyenera kudziwidwa kuti tryptophan muzakudya simatengedwa 100% ndikugwiritsidwa ntchito. Panthawi imodzimodziyo, kuwonjezereka kwa mlingo waukulu wa tryptophan (monga kupitirira 500mg/kg) kungayambitse kuwonongeka kwa impso. Chifukwa chake, muzakudya zatsiku ndi tsiku, zowonjezera zowonjezera za tryptophan zitha kukhala, osalimbikitsa kugwiritsa ntchito kwambiri tryptophan supplements.

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Kuphatikiza apo, kuchita masewera olimbitsa thupi pang'ono monga kuthamanga, kusambira, yoga, ndi zina zambiri, kungathandizenso kukulitsa kuchuluka kwa tryptophan ndi serotonin kaphatikizidwe m'thupi, kuthetsa kupsinjika ndikusintha malingaliro. Kugona mokwanira, kukhala ndi maganizo abwino ndi oyembekezera zinthu zabwino, ndiponso kuphunzira kufotokoza zakukhosi moyenerera ndi njira zothandiza kwambiri zothanirana ndi kupsinjika maganizo. Mukakumana ndi zovuta zazikulu zamalingaliro monga kukhumudwa ndi nkhawa, ndikofunikira kupeza chithandizo chamankhwala munthawi yake.

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Pomaliza, phunziroli likuwonetsa momwe amadyera m'malingaliro chifukwa cha kupsinjika kwanthawi yayitali kuchokera pamalingaliro a tryptophan metabolism, ndipo amapereka malingaliro atsopano ochepetsa kupsinjika, kuwongolera kusokonezeka kwamalingaliro ndi kupsinjika kwa thupi. Ngakhale kuti maphunziro owonjezera a kuchuluka kwa anthu amafunikira kuti muwongolere mlingo ndi nthawi ya tryptophan supplementation muzakudya, zotsatira za kafukufukuyu zatipatsa malingaliro atsopano olimbikitsa thanzi lakuthupi ndi m'maganizo kudzera muzakudya. Timakhulupirira kuti kudya zakudya zopatsa thanzi, kuchita masewera olimbitsa thupi moyenera, kugona bwino komanso kuthana ndi nkhawa, titha kuthana ndi zovuta za moyo ndikukhala ndi tsogolo labwino.