Isu tose tinoziva kuti kushushikana kwenguva refu kunogona kutungamirira kumatambudziko ehutano hwepanyama uye hwepfungwa, zvakadai sekuzvidya mwoyo, kuora mwoyo uye mamwe manzwiro asina kunaka, pamwe nekusagadzikana kwechido, kurema uye mamwe matambudziko emagetsi. Vanhu vazhinji mukutarisana nekushungurudzika, vacharatidza kudya kwemanzwiro (kudya kwemanzwiro), ndiko kuti, nekudya zvakanyanya kubvisa manzwiro asina kunaka anokonzerwa nekushungurudzika. Kudya kwepfungwa kunowanzo kuperekedzwa nemakoriori akawandisa, inova imwe yenjodzi yekufutisa. Saka, ndeipi nzira iyo kushungurudzika kunokonzera kusagadzikana kwekudya? Ndehupi hukama pakati pe tryptophan metabolism uye kusagadzikana-kukonzeresa manzwiro ekudya? Kuti vagadzirise matambudziko aya, vatsvakurudzi vakaita nhevedzano yekuongorora kwakadzama.

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Tryptophan imwe yeamino acids yakakosha mumuviri wemunhu uye inotangira neurotransmitter 5-hydroxytryptophan (5-HT, inozivikanwawo se serotonin) muuropi. Nhamba huru yezvidzidzo zvakaratidza kuti tryptophan metabolism disorders yakabatana zvikuru nezvirwere zvakasiyana-siyana zvepfungwa, zvakadai sekuora mwoyo, kuzvidya mwoyo, schizophrenia nezvimwe zvakadaro. Panguva imwecheteyo, tryptophan uye metabolite yayo 5-HT inobatanidzwawo mukugadzirisa kwechido uye simba rekuenzanisa. Saka, pasi pemamiriro ekushushikana kusingaperi, tryptophan metabolism inoshanduka here? Shanduko iyi ine chekuita neabnormal stress-induced eating behavior? Nemibvunzo iyi mupfungwa, vatsvakurudzi vakaita rutsva rweongororo dzakadzama.

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Kutanga, vatsvakurudzi vakashandisa mbeva kuti vagadzire chimiro chisingagumi-chinokonzera manzwiro ekudya (CMS). Vakaisa mbeva kune zvakasiyana-siyana zvinyoro zvisingafungidzike zvinonetsa, senge kuvharirwa, kuzunungusa makeji, uye mabhati emvura inotonhora, kwemazuva makumi maviri nenomwe akateedzana kutevedzera zvinoramba zvichinetsa, zvakasiyana siyana muhupenyu chaihwo. Mhedzisiro yacho yakaratidza kuti mushure memazuva e21 ekushushikana kusingaperi, mbeva dzakaratidza kushushikana kukuru uye hunhu hwekuora mwoyo. Muchiedza chevhu rakavhurika (OFT), nguva yeboka reCMS mbeva dzinogara munzvimbo yepakati penzvimbo yakazaruka yakapfupikiswa zvakanyanya, zvichiratidza kuti kushushikana kwavo kwakawedzera. Mukuedza kwekurembera muswe (TST), nguva yekutamburira mbeva muboka reCMS yakapfupikiswa zvakanyanya, zvichiratidza kuwedzera kwekusava netariro. Panguva imwecheteyo, kudya kwemakonzo muboka reCMS kwakawedzera zvakanyanya, asi uremu hwakaderera zvakanyanya, zvichiratidza kuti kuda kwavo uye metabolism zvakakanganiswa.

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Mushure meizvozvo, vaongorori vakaita yakanangwa metabolomic ongororo yeiyo tryptophan metabolic nzira muguva serum. Zvigumisiro zvakaratidza kuti serum tryptophan yeCMS yeboka mbeva yakaderera zvakanyanya, nepo yakadzika metabolites 5-hydroxytryptamine (5-HT) uye kynurenine zviri mukati zvakawedzera zvakanyanya. Kumwe kuongorora kwakaratidza kuti mRNA kutaura kwe tph1, enzyme inokosha mukugadzirwa kwe5-hydroxytryptamine, yakanyanya kuderedzwa mumakonzo emakonzo muboka reCMS, uye zvinyorwa zve5-HT mukoloni zvakaratidzawo kuderera. Izvi zvinoratidza kuti kusagadzikana kusingaperi kunokanganisa homeostasis ye tryptophane-5-HT metabolic nzira mumatumbo emakonzo, zvichikonzera kusaenzana kweparipheral 5-HT mazinga.

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Kunyange zvazvo tryptophan isingagoni kupfuudza zvakananga ropa-brain barriers, metabolite yayo 5-HT inobata basa rinokosha seyeurotransmitter mukati mehutano hwehutano uye inobatanidzwa mukugadzirisa maitiro akawanda ehupenyu akadai semafungiro, cognition uye kudya. Vatsvakurudzi vakaongororazve shanduko mukutaura kweanoverengeka neuropeptides uye 5-HT receptors inobatanidzwa mukugadzirisa chido mu hypothalamus. Mhedzisiro yacho yakaratidza kuti kusagadzikana kusingaperi kwakadzora zvakanyanya kutaura kwechido chekusimudzira neuropeptides senge AgRP uye OX1R, uku ichidzikisira kutaura kwe appetiteinhibiting zvinhu zvakaita se LEPR, MC4R uye 5-HT1B. Izvi zvinoratidza kuti kukanganisa kwetryptophane-5-HT nzira kunogona kutungamirira kune maitiro asina kunaka ekudya nekukanganisa hypothalamic neural circuit.

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Saka, kuwedzeredza ne tryptophan kudzoreredza kusagadzikana-kukonzeresa mafungiro uye maitiro ekudya abnormalities? Mishonga miviri ye tryptophan (100mg/kg uye 300mg/kg) yaipihwa CMS mbeva negavage yezuva nezuva kwemazuva 21. Zvigumisiro zvakaratidza kuti mushure memazuva e21 ekupindira nehuwandu hwe tryptophan (300mg / kg), kuzvidya mwoyo uye kuora mwoyo-kufanana nemafambiro emakonzo munzvimbo yakazaruka yekuedza uye kuedza kwekumiswa kwemuswe kwakagadziridzwa zvakanyanya, uye kuwedzera kusina kujairika kwekudya kwekudya uye kuora kurasikirwa kwakagadziriswa. Zvimwe zvidzidzo zvakaratidza kuti kupindira kwe-high-dose tryptophan kunogona kuvharidzira kukwira-kutonga kwechido chekusimudzira zvinhu zvakadai seAgRP uye OX1R mu hypothalamus inokonzerwa nekusingaperi kushungurudzika, apo kudzorera kutaura kwechido chinodzivisa zvinhu zvakadai LEPR, MC4R, 5-HT1B uye 5-HT2C. Zvakakosha kucherechedza kuti kunyange zvazvo dhigirii yakaderera ye tryptophan (100mg/kg) boka haina kuratidza kuvandudzwa kwakakosha muzviratidziro zvekuzvibata, pakanga paine maitiro ekuchinja mu hypothalamic appetite inoenderana nejini kutaura pa molecular level.

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Zvimwe zvidzidzo zvemamolecular mechanics zvakaratidza kuti 5-HT, nekusunga 5-HT1B uye 5-HT2C receptors pa hypothalamic POMC, AgRP nedzimwe neurons, inhibits AgRP/NPY neurons inosimudzira kudya, inomutsa POMC neurons inodzivisa kudya uye kukurudzira kushandiswa kwesimba, uyezve inoita basa rekudya uye kudzora uremu. Izvi zvinopa zvakakosha mamolekyuli erutsigiro rwekuvandudza kwekudyisa manzwiro ne tryptophan-5-HT nzira.

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Vatsvagiri vakashandisawo mbeva hypothalamic neuron cell line GT1-7 kuti vaenderere mberi nekuona kudzora maitiro e5-HT pane appetite ine hukama neuropeptides. Vakabata GT1-7 maseru ane 10μM yecorticosterone (CORT) kwemaawa makumi maviri nemana kutevedzera kusingaperi kusagadzikana mamiriro. Mhedzisiro yacho yakaratidza kuti kutaura kwechido chekusimudzira majini akadai seAgRP neOX1R kwakanyatso kudzorwa neCORT kurapwa, ukuwo kutaura kwechido kuvharisa majini akadai seMC4R, 5-HT1B uye 5-HT2C yaive yakadzikira. Mushure mekutanga kurapwa ne0.1μM 5-HT kwemaawa maviri, kutaura kusina kujairika kweCORt-induced AgRP nemamwe majini kunogona kudzoreredzwa zvakanyanya, uye kutaura kweMC4R, 5-HT1B uye 5-HT2C kunogona kudzoserwa. Izvi zvakasimbisazve kurongeka kwakananga kwe5-HT pane hypothalamic neurons.

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Pfupiso yedata:

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Migumisiro yekusingaperi kushungurudzika pa tryptophan metabolism homeostasis mumakonzo: Kushungurudzika kusingaperi kwakakonzera serum tryptophan mazinga kuderera (P

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Mhedzisiro yetryptophan pakuda kudya uye kuora mwoyo-kufanana nemaitiro anokonzerwa nekushungurudzika kusingaperi: High-dose tryptophan supplementation yakadzoreredza maitiro asina kujairika ekudya uye kurasikirwa uremu kunokonzerwa nekushushikana kusingaperi (P

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Migumisiro ye tryptophan supplementation pane hypothalamic feeding neurons uye appetite regulators mukusingaperi kushungurudzika mice: Immunohistochemical staining yakaratidza kuti kutaura kwe c-fos uye AgRP munharaunda yeARC ye hypothalamus muboka rekushungurudzika kwekusingaperi kwakawedzera zvakanyanya, asi kutaura kwe LEPR kwakaderera zvikuru (P

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Migumisiro ye tryptophan pa 5-HT metabolic pathway mu hypothalamus yekusingaperi kushungurudzika mice: Serum tryptophan uye 5-HT mazinga akawedzerwa zvakanyanya mushure me tryptophan supplementation (P

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Kakawanda, chidzidzo ichi chinoratidza kuti kusagadzikana kusingaperi kunokonzera kukanganisa kwe hypothalamic appetite regulatory network nekuvhiringidza tryptophane-5-HT metabolic nzira, iyo inokonzera kudya kwemanzwiro. Kuwedzerwa kwetryptophan yekunze, kunyanya mumatareji akakwirira (300mg/kg), inodzorera mazinga epakati e5-HT, inomutsa hypothalamic 5-HT1B uye 5-HT2C receptors, inhibits AgRP/NPY neurons, inomutsa POMC neurons, uye inovandudza kushungurudzika-kune hukama hwepfungwa uye kusagadzikana kwekudya maitiro.

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Mhedzisiro iyi yetsvagurudzo ine kukosha kwakakosha kunoshanda. Muhupenyu hwanhasi hwekumhanya-mhanya, hwekunetsekana kwakanyanya, vanhu vazhinji vakatarisana nekushushikana-kukonzeresa nyaya dzepfungwa uye uremu kusagadzikana. Zvidzidzo zvakaratidza kuti kushushikana kwenguva refu kunokonzera kuti tryptophan yemuviri iderere, 5-hydroxytryptamine synthesis iderere, uye zvino inotungamira kune dzakatevedzana neuroendocrine kusagadzikana, izvo zvinotungamira mukuora mwoyo, kufunganya uye mamwe manzwiro asina kunaka, pamwe ne hyperappetite, kufutisa uye mamwe matambudziko emetabolic. Ichi chidzidzo chinoratidza basa repakati re tryptophan uye metabolite yayo 5-hydroxytryptophan mu-stress-emotion-appetite regulation axis, ichipa mazano matsva uye nzira dzekubvisa kushushikana uye kuvandudza kusagadzikana kwemafungiro uye kuora mwoyo.

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Kubva pane zvakawanikwa, vaongorori vanopa mamwe mazano ezvekudya kubatsira vanhu kurarama zviri nani nekushushikana. Chekutanga pane zvese, iyo yakakodzera yekuwedzera ye tryptophan yakapfuma chikafu mukudya kwezuva nezuva, senge mazai, chizi, nzungu, mabhanana, oats, nezvimwewo, inogona kubatsira kuvandudza mwero we tryptophan mumuviri, kukurudzira synthesis ye5-hydroxytryptophan, nekudaro kuvandudza mamiriro emanzwiro uye kudzivisa kushushikana kwekudya. Nekudaro, zvinofanirwa kucherechedzwa kuti tryptophan muchikafu haisi 100% inotorwa uye inoshandiswa. Panguva imwecheteyo, yenguva yakareba yakakura yekuwedzera yekuwedzera ye tryptophan (yakadai seinopfuura 500mg/kg) inogona kukonzera kukuvara kweitsvo. Naizvozvo, muchiyero chemazuva ese chekudya, ine mwero yekuwedzera ye tryptophan inogona kunge iri, usatsigirire kushandiswa kwakanyanya kwetryptophan supplements.

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Uye zvakare, kurovedza muviri zvine mwero sekumhanya, kushambira, yoga, nezvimwewo, kunogonawo kubatsira kuwedzera nhanho ye tryptophan uye serotonin synthesis mumuviri, kubvisa kushushikana uye kugadzirisa manzwiro. Kurara zvakakwana, kuva nemafungiro akanaka uye ane tariro, uye kudzidza kutaura manzwiro ane musoro inzira dzinoshanda dzokukunda nadzo kunetseka. Paunenge uchitarisana nezvinetso zvakakomba zvepfungwa zvakadai sekuora mwoyo uye kufunganya, zvinodikanwa kutsvaga kurapwa kwehunyanzvi hwepfungwa nenguva.

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Mukupedzisa, chidzidzo ichi chinoratidza nzira yekudya kwemanzwiro kunokonzerwa nekushungurudzika kusingaperi kubva pakuona kwe tryptophan metabolism, uye inopa maonero matsva ekuderedza kushungurudzika, kuvandudza mafungiro emafungiro uye kuora mwoyo. Kunyangwe zvimwe zvidzidzo zvehuwandu zvichidikanwa kukwirisa dosi uye nguva yekuwedzera tryptophan mukudya, mhedzisiro yechidzidzo ichi yakatipa mazano matsva ekusimudzira hutano hwemuviri nepfungwa kuburikidza nekudya. Tinotenda kuti kuburikidza nekudya kwakadzikama, maekisesaizi ari pakati nepakati, kurara kwakanaka uye kugadzirisa manzwiro akanaka, tinogona kutarisana nedzvinyiriro yeupenyu takadzikama uye kugamuchira ramangwana riri nani.