Sonke siyazi ukuba uxinzelelo lwexesha elide lunokukhokelela kuluhlu lweengxaki zempilo yengqondo kunye nengqondo, ezifana nokuxhalaba, ukudandatheka kunye nezinye iimvakalelo ezimbi, kunye nokuphazamiseka kokutya, ukuphazamiseka kwesisindo kunye nezinye iingxaki ze-metabolic. Abantu abaninzi xa bejamelene noxinzelelo, baya kubonisa ukutya ngokweemvakalelo (ukutya ngokweemvakalelo), oko kukuthi, ngokutya kakhulu ukukhulula iimvakalelo ezimbi ezibangelwa luxinzelelo. Ukutya ngokweemvakalelo kudla ngokukhatshwa ziicalories ezigqithisileyo, nto leyo yenye yezinto ezibeka umngcipheko wokutyeba ngokugqithiseleyo. Ke, yeyiphi inkqubo apho uxinzelelo lubangela ukuphazamiseka kokutya? Yintoni ubudlelwane phakathi kwe-tryptophan metabolism kunye nokutya okubangelwa uxinzelelo? Ukucombulula ezi ngxaki, abaphandi baye benza uthotho lohlolisiso oluneenkcukacha.

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I-Tryptophan yenye yee-amino acids ezibalulekileyo emzimbeni womntu kunye ne-precursor ye-neurotransmitter 5-hydroxytryptophan (5-HT, eyaziwa ngokuba yi-serotonin) kwingqondo. Inani elikhulu lezifundo libonise ukuba i-tryptophan metabolism disorders inxulumene ngokusondeleyo neentlobo zezifo zengqondo, ezifana nokudakumba, ukuxhalaba, i-schizophrenia njalo njalo. Ngelo xesha, i-tryptophan kunye ne-5-HT yayo ye-metabolite nayo ibandakanyeka ekulawuleni ukutya kunye nokulinganisela kwamandla. Ke, phantsi kweemeko zoxinzelelo olungapheliyo, ngaba i-tryptophan metabolism iyatshintsha? Ngaba olu tshintsho lunxulumene noxinzelelo olungaqhelekanga kwindlela yokuziphatha yokutya? Benale mibuzo engqondweni, abaphandi baqhube uthotho lweemvavanyo ezineenkcukacha.

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Okokuqala, abaphandi basebenzisa iigundane ukuphuhlisa imodeli engapheliyo yokutya okubangelwa uxinzelelo lwengqondo (CMS). Baye babeka iimpuku kwiintlobo ezahlukeneyo zoxinzelelo olungalindelekanga, olufana noxinzelelo lokuvalelwa, iikheji ezishukumayo, kunye neebhafu zamanzi abandayo, kangangeentsuku ezingama-21 ezilandelelanayo ukulinganisa uxinzelelo oluqhubekayo, olwahlukeneyo ebomini bokwenyani. Iziphumo zabonisa ukuba emva kweentsuku ezingama-21 zoxinzelelo olungapheliyo, iimpuku zibonise ukuxhalaba okubalulekileyo kunye nokuziphatha okunje ngoxinzelelo. Kuvavanyo lwendawo evulekileyo (OFT), ixesha leqela le-CMS leempuku ezihlala kwindawo ephakathi kwibala elivulekileyo lancitshiswa kakhulu, libonisa ukuba izinga labo lokuxhalaba liye landa. Kuvavanyo lokuxhoma umsila (TST), ixesha lomzabalazo leempuku kwiqela le-CMS lancitshiswa kakhulu, libonisa ukwanda kokungabi nathemba. Ngelo xesha, ukutya okudliwayo kweegundane kwiqela le-CMS kwanda kakhulu, kodwa ubunzima buyancipha kakhulu, bubonisa ukuba ukutya kwabo kunye nemetabolism kuphazamisekile.

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Emva koko, abaphandi benza uhlalutyo lwemetabolomic ekujoliswe kuyo kwindlela ye-tryptophan metabolic kwiserum yemouse. Iziphumo zibonise ukuba umxholo we-serum tryptophan yeegundane zeqela le-CMS zancipha kakhulu, ngelixa i-metabolites ephantsi kwe-5-hydroxytryptamine (5-HT) kunye neziqulatho ze-kynurenine zanda kakhulu. Uhlalutyo olongezelelweyo lubonise ukuba ukubonakaliswa kwe-mRNA ye-tph1, i-enzyme ephambili kwi-synthesis ye-5-hydroxytryptamine, yayilawulwa kakhulu kwi-colon tissue yeegundane kwiqela le-CMS, kunye nomxholo we-5-HT kwikholoni ubonise ukuhla. Oku kuphakamisa ukuba uxinzelelo olungapheliyo luphazamisa i-homeostasis ye-tryptophane-5-HT ye-metabolism kwindlela yamathumbu emathunjini, okubangela ukungalingani kwe-peripheral 5-HT amanqanaba.

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Nangona i-tryptophan ayinakudlula ngokuthe ngqo umqobo wegazi-ingqondo, i-metabolite yayo i-5-HT idlala indima ebalulekileyo njenge-neurotransmitter kwinkqubo ye-nervous central kwaye ibandakanyeka ekulawuleni iinkqubo ezininzi ze-physiological ezifana ne-mood, cognition and eating. Abaphandi bahlalutya ngakumbi utshintsho kwintetho yee-neuropeptides ezininzi kunye ne-5-HT receptors ezibandakanyekayo kulawulo lokutya kwi-hypothalamus. Iziphumo zibonise ukuba uxinzelelo olungapheliyo lulawule kakhulu ukubonakaliswa kwe-appetitepromoting neuropeptides ezifana ne-AgRP kunye ne-OX1R, ngelixa kunciphisa ukubonakaliswa kwezinto ezinokuthi zithintele ezifana ne-LEPR, MC4R kunye ne-5-HT1B. Oku kuphakamisa ukuba ukuphazamiseka kwendlela ye-tryptophane-5-HT kunokukhokelela ekuziphatheni okungaqhelekanga kokutyisa ngokuchaphazela i-hypothalamic neural circuit.

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Ke, ngaba ukongeza nge-tryptophan kunokukhulula imo engapheliyo ebangelwa kuxinzelelo kunye nokutya okungaqhelekanga? Iidosi ezimbini ze-tryptophan (100mg / kg kunye ne-300mg / kg) zalawulwa kwiigundane ze-CMS nge-gavage yemihla ngemihla yeentsuku ze-21. Iziphumo zibonise ukuba emva kweentsuku ze-21 zokungenelela kunye nedosi ephezulu ye-tryptophan (300mg / kg), ukuxhalaba kunye nokuziphatha okunjengokudakumba kweegundane ekulingweni kwebala elivulekileyo kunye novavanyo lokumisa umsila kwaphuculwa kakhulu, kwaye okungaqhelekanga kokunyuka kokutya kunye nokulahlekelwa kwesisindo kwalungiswa. Uphononongo olongezelelweyo lubonise ukuba i-dose ephezulu ye-tryptophan ingenelelo inokuthintela ukunyuswa kwe-appetite ekhuthaza izinto ezifana ne-AgRP kunye ne-OX1R kwi-hypothalamus ebangelwa uxinzelelo olungapheliyo, ngelixa libuyisela ukubonakaliswa komdla wokuthintela izinto ezifana ne-LEPR, i-MC4R, i-5-HT1B kunye ne-5-HT2C. Kuyaphawuleka ukuba nangona i-dose ephantsi ye-tryptophan (100mg / kg) iqela alizange libonise ukuphucuka okuphawulekayo kwizibonakaliso zokuziphatha, kukho umzila weenguqu kwi-hypothalamic appetite ehambelana ne-gene expression kwinqanaba le-molecular.

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Uphando olongezelelweyo lwe-molecular mechanism lubonise ukuba i-5-HT, ngokubophelela i-5-HT1B kunye ne-5-HT2C i-receptors kwi-hypothalamic POMC, i-AgRP kunye nezinye ii-neurons, inqanda i-AgRP/NPY neurons ekhuthaza umdla, isebenze i-neurons ye-POMC evimbela ukutya kunye nokukhuthaza ukusetyenziswa kwamandla, kwaye emva koko idlala indima ye-appet ekulawuleni ubunzima. Oku kubonelela ngenkxaso ye-molecular mechanism ebalulekileyo ekuphuculeni ukondla ngokweemvakalelo nge-tryptophan-5-HT indlela.

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Abaphandi baphinde basebenzise i-mouse ye-hypothalamic neuron cell line GT1-7 ukuqhubela phambili nokuqinisekisa isiphumo solawulo lwe-5-HT kwi-neuropeptides enxulumene nomdla. Baphatha iiseli ze-GT1-7 nge-10μM ye-corticosterone (CORT) kwiiyure ezingama-24 ukulinganisa iimeko zoxinzelelo olungapheliyo. Iziphumo zibonise ukuba ukubonakaliswa komdla wokukhuthaza izakhi zofuzo ezifana ne-AgRP kunye ne-OX1R yayiphezulu-ilawulwa ngonyango lwe-CORT, ngelixa ukubonakaliswa komdla wokuthintela izakhi zofuzo ezifana ne-MC4R, i-5-HT1B kunye ne-5-HT2C yayilawulwa phantsi. Emva kokunyangwa kwangaphambili nge-0.1μM 5-HT kwiiyure ze-2, ukubonakaliswa okungaqhelekanga kwe-CORt-induced AgRP kunye nezinye iijini zinokuguqulwa kakhulu, kwaye inkcazo ye-MC4R, 5-HT1B kunye ne-5-HT2C inokubuyiselwa. Oku kuqinisekisile ngakumbi umphumo wokulawula ngokuthe ngqo we-5-HT kwi-hypothalamic neurons.

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Isishwankathelo sedatha:

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Iziphumo zokuxinezeleka okungapheliyo kwi-tryptophan metabolism homeostasis kwiigundane: Uxinzelelo olungapheliyo lwabangela ukuba amanqanaba e-serum tryptophan anciphise (P

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Umphumo we-tryptophan kwi-appetite kunye nokuziphatha okunjengokudakumba okubangelwa kukuxinezeleka okungapheliyo: I-tryptophan supplementation ye-dose ephezulu ibuyisele ukuziphatha okungaqhelekanga kokutya kunye nokunciphisa umzimba okubangelwa uxinzelelo olungapheliyo (P

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Iziphumo ze-tryptophan supplementation kwi-hypothalamic feed neurons kunye nabalawuli be-appetite kwiigundane ezixinzelelekileyo ezingapheliyo: I-Immunohistochemical staining ibonise ukuba ukubonakaliswa kwe-c-fos kunye ne-AgRP kwingingqi ye-ARC ye-hypothalamus kwiqela loxinzelelo olungapheliyo kwanda kakhulu, ngelixa ukubonakaliswa kwe-LEPR kwancipha kakhulu (P

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Iziphumo ze-tryptophan kwi-5-HT ye-metabolic pathway kwi-hypothalamus yeegundane ezixinzelelekileyo: I-Serum tryptophan kunye ne-5-HT amanqanaba anyuswe kakhulu emva kokuxhaswa kwe-tryptophan (P

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Ngokubanzi, olu pho nonongo lubonisa ukuba uxinzelelo olungapheliyo lubangela ukuphazamiseka kwenethiwekhi yokulawula i-hypothalamic appetite ngokuphazamisa i-tryptophane-5-HT ye-metabolic pathway, ebangela ukuba idle ngokweemvakalelo. Ukongezwa kwe-tryptophan yangaphandle, ngokukodwa kwiidosi eziphezulu (300mg / kg), kubuyisela amanqanaba e-5-HT aphakathi, kusebenze i-hypothalamic 5-HT1B kunye ne-5-HT2C receptors, inqanda i-AgRP/NPY neurons, isebenze i-POMC neurons, kwaye iphucula ukuphazamiseka kwemizwelo ehambelana noxinzelelo kunye nokuziphatha okungaqhelekanga kokutya.

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Esi siphumo sophando sinokubaluleka okusebenzayo okubalulekileyo. Kubomi banamhlanje obukhawulezayo, obunoxinzelelo olukhulu, abantu abaninzi bajongene nemiba yeemvakalelo ebangelwa luxinzelelo kunye nokuphazamiseka kobunzima. Uphononongo lubonise ukuba uxinzelelo lwexesha elide lubangela ukuba izinga le-tryptophan lomzimba lihle, i-5-hydroxytryptamine synthesis iyancipha, kwaye emva koko ikhokelele kuthotho lweengxaki ze-neuroendocrine, ezikhokelela ekudakaleni, ukuxhalaba kunye nezinye iimvakalelo ezimbi, kunye ne-hyperappetite, ukutyeba kunye nezinye iingxaki ze-metabolic. Olu pho nonongo lubonisa indima ephambili ye-tryptophan kunye ne-metabolite yayo ye-5-hydroxytryptophan kwi-axis yokulawula i-stress-emotion-appetite, ukubonelela ngeengcamango ezintsha kunye neendlela zokunciphisa uxinzelelo kunye nokuphucula ukuphazamiseka kwemizwelo kunye nokuphazamiseka kwesisindo.

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Ngokusekwe kwiziphumo, abaphandi banikezela ngeengcebiso ezithile zokutya ukunceda abantu bajongane ngcono noxinzelelo. Okokuqala, isongezelelo esifanelekileyo sokutya okutyebileyo kwe-tryptophan kwisidlo semihla ngemihla, njengamaqanda, itshizi, amandongomane, iibhanana, i-oats, njl., kunokunceda ukuphucula inqanaba le-tryptophan emzimbeni, ukukhuthaza ukuhlanganiswa kwe-5-hydroxytryptophan, ngaloo ndlela kuphuculwe imeko yeemvakalelo kunye nokuthintela uxinzelelo lokutya. Nangona kunjalo, kufuneka kuqatshelwe ukuba i-tryptophan ekutyeni ayi-100% ifunxa kwaye isetyenziswe. Kwangaxeshanye, ixesha elide idosi eyongezelelweyo ye-tryptophan (efana nangaphezulu kwe-500mg/kg) inokubangela umonakalo kwizintso. Ke ngoko, kwibhalansi yokutya yemihla ngemihla, ukongezelela okuphakathi kwe-tryptophan kunokuba, musa ukukhuthaza ukusetyenziswa ngokugqithisileyo kwezongezo ze-tryptophan.

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Ukongeza, ukuzilolonga okuphakathi okunje ukubaleka, ukuqubha, i-yoga, njl. njl., kunokunceda ukwandisa inqanaba le-tryptophan kunye ne-serotonin synthesis emzimbeni, ukunciphisa uxinzelelo kunye nokuphucula imo. Ukulala ngokwaneleyo, ukuba nesimo sengqondo esikhuthazayo nokuba nethemba, nokufunda ukuchaza iimvakalelo ngendlela esengqiqweni zonke ziindlela ezisebenzayo zokuhlangabezana noxinezeleko. Xa ujongene neengxaki ezinzulu zeemvakalelo ezifana nokudakumba kunye nokuxhalaba, kuyimfuneko ukufuna unyango lwengqondo yobuchwephesha ngexesha.

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Ukuqukumbela, olu phononongo lubonisa indlela yokutya ngokweemvakalelo okubangelwa kukuxinezeleka okungapheliyo ukusuka kumbono we-tryptophan metabolism, kwaye ibonelela ngombono omtsha wokuphelisa uxinzelelo, ukuphucula ukuphazamiseka kwemizwelo kunye nokuphazamiseka kobunzima. Nangona uphando lwabemi olongezelelweyo lufuneka ukwandisa umthamo kunye nobude be-tryptophan supplementation ekutyeni, iziphumo zolu phononongo zisinike imibono emitsha yokukhuthaza impilo yomzimba nengqondo ngolawulo lokutya. Sikholelwa ukuba ngokutya okunesondlo, umthambo ophakathi, ukulala kakuhle kunye nokumelana neemvakalelo ngendlela eyakhayo, sinokujamelana ngokuzolileyo noxinzelelo lobomi kwaye samkele ikamva elingcono.