Sonke siyazi ukuthi ukucindezeleka isikhathi eside kungaholela ochungechungeni lwezinkinga zempilo ngokomzimba nangokwengqondo, njengokukhathazeka, ukucindezeleka kanye neminye imizwelo engalungile, kanye nokuphazamiseka kwesifiso sokudla, ukuphazamiseka kwesisindo nezinye izinkinga ze-metabolic. Abantu abaningi lapho bebhekene nokucindezeleka, bazobonisa ukudla ngokomzwelo (ukudla ngokomzwelo), okungukuthi, ngokudla kakhulu ukuze bakhulule imizwelo emibi ebangelwa ukucindezeleka. Ukudla okungokomzwelo kuvame ukuhambisana nama-kilojoule amaningi, okungenye yezinto eziyingozi yokukhuluphala. Ngakho-ke, iyiphi indlela ukucindezeleka kubangela ukuphazamiseka kwesifiso sokudla? Buyini ubudlelwano phakathi kwe-tryptophan metabolism kanye nokudla okungokomzwelo okubangelwa ukucindezeleka? Ukuze baxazulule lezi zinkinga, abacwaningi baye benza uchungechunge lokuhlola okuningiliziwe.

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I-Tryptophan ingenye yama-amino acid abalulekile emzimbeni womuntu kanye nesandulela se-neurotransmitter 5-hydroxytryptophan (5-HT, eyaziwa nangokuthi i-serotonin) ebuchosheni. Inani elikhulu lezifundo libonise ukuthi ukuphazamiseka kwe-tryptophan metabolism kuhlobene eduze nezifo ezihlukahlukene zengqondo, njengokucindezeleka, ukukhathazeka, i-schizophrenia nokunye. Ngesikhathi esifanayo, i-tryptophan kanye ne-5-HT yayo ye-metabolite nayo ihileleke ekulawuleni ukudla kanye nokulinganisela kwamandla. Ngakho-ke, ngaphansi kwezimo zokucindezeleka okungapheli, ingabe i-tryptophan metabolism iyashintsha? Ingabe lolu shintsho luhlobene nokuziphatha kokudla okubangelwa ukucindezeleka okungavamile? Benale mibuzo engqondweni, abacwaningi benza uchungechunge lwezivivinyo ezinemininingwane.

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Okokuqala, abacwaningi basebenzise amagundane ukuthuthukisa imodeli yokudla engokomzwelo engapheli (CMS). Bafaka amagundane ezingcindezini ezihlukahlukene ezingalindelekile, njengokucindezeleka kokuvalelwa, amakheji anyakazayo, nokugeza kwamanzi abandayo, izinsuku ezingu-21 ezilandelanayo ukuze balingise izingcindezi eziphikelelayo, ezihlukahlukene ekuphileni kwangempela. Imiphumela yabonisa ukuthi ngemva kwezinsuku ezingu-21 zokucindezeleka okungapheli, amagundane abonisa ukukhathazeka okukhulu nokuziphatha okufana nokucindezeleka. Esivivinyweni senkundla evulekile (OFT), isikhathi samagundane eqembu le-CMS ahlala endaweni emaphakathi yenkundla evulekile safinyezwa kakhulu, okubonisa ukuthi izinga lawo lokukhathazeka lenyukile. Ocwaningweni lokulenga umsila (TST), isikhathi somzabalazo samagundane eqenjini le-CMS safinyezwa kakhulu, okuphakamisa umuzwa okhulayo wokuphelelwa ithemba. Ngesikhathi esifanayo, ukudla kwamagundane eqenjini le-CMS kwanda kakhulu, kodwa isisindo sehla kakhulu, okuphakamisa ukuthi ukudla kwabo kanye nemetabolism kuphazamisekile.

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Kamuva, abacwaningi benza ukuhlaziya okuhlosiwe kwe-metabolomic yendlela ye-tryptophan metabolic ku-serum yegundane. Imiphumela ibonise ukuthi okuqukethwe kwe-serum tryptophan yamagundane eqembu le-CMS kwehle kakhulu, kuyilapho i-metabolites engezansi i-5-hydroxytryptamine (5-HT) nokuqukethwe kwe-kynurenine kwanda kakhulu. Ukuhlaziywa okwengeziwe kubonise ukuthi inkulumo ye-mRNA ye-tph1, i-enzyme eyinhloko ekuhlanganiseni kwe-5-hydroxytryptamine, yayilawulwa phansi kakhulu ku-colon tissue yamagundane eqenjini le-CMS, futhi okuqukethwe kwe-5-HT kukholoni nakho kubonise umkhuba ophansi. Lokhu kuphakamisa ukuthi ukucindezeleka okungapheli kuphazamisa i-homeostasis yendlela ye-tryptophane-5-HT ye-metabolic emathunjini amagundane, okuholela ekungalinganini kwamazinga we-peripheral 5-HT.

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Nakuba i-tryptophan ingakwazi ukudlula ngokuqondile umgoqo wegazi-ubuchopho, i-metabolite yayo i-5-HT idlala indima ebalulekile njenge-neurotransmitter ohlelweni lwezinzwa oluphakathi futhi ihileleke ekulawuleni izinqubo eziningi zomzimba ezifana nemizwa, ukuqonda nokudla. Abacwaningi baphinde bahlaziya izinguquko ekukhulumeni kwama-neuropeptides amaningana kanye nama-receptors e-5-HT abandakanyeka ekulawulweni kwesifiso sokudla ku-hypothalamus. Imiphumela yabonisa ukuthi ukucindezeleka okungapheli kulawule ngokuphawulekayo ukubonakaliswa kwesifiso sokudla esikhuthaza ama-neuropeptides njenge-AgRP ne-OX1R, kuyilapho yehlisa ukubonakaliswa kwezinto ezivimbela ukudla njenge-LEPR, MC4R kanye ne-5-HT1B. Lokhu kuphakamisa ukuthi ukuphazamiseka kwendlela ye-tryptophane-5-HT kungase kuholele ekuziphatheni okungavamile kokudla ngokuthinta i-hypothalamic neural circuit.

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Ngakho-ke, ingabe ukwengezwa nge-tryptophan kungasikhulula isimo sengqondo esibangelwa ukucindezeleka okungapheli kanye nokuziphatha okungavamile? Imithamo emibili ye-tryptophan (100mg/kg kanye ne-300mg/kg) yanikezwa amagundane e-CMS nge-gavage yansuku zonke izinsuku ezingama-21. Imiphumela yabonisa ukuthi ngemva kwezinsuku ezingu-21 zokungenelela ngesilinganiso esiphezulu se-tryptophan (300mg/kg), ukuziphatha okunjengokukhathazeka nokucindezeleka kwamagundane ekuhloleni indawo evulekile nokuhlolwa kokumiswa komsila kwathuthukiswa kakhulu, futhi ukudla okungavamile okwandisiwe nokuncipha kwesisindo kwalungiswa. Ucwaningo olwengeziwe lubonise ukuthi ukungenelela komthamo ophezulu we-tryptophan kungavimbela ukulawulwa okuphezulu kwezinto ezikhuthaza ukudla okufana ne-AgRP ne-OX1R ku-hypothalamus ebangelwa ukucindezeleka okungapheli, kuyilapho kubuyisela ukubonakaliswa kwezinto ezivimbela isifiso sokudla njenge-LEPR, MC4R, 5-HT1B kanye ne-5-HT2C. Kuyaphawuleka ukuthi nakuba umthamo ophansi weqembu le-tryptophan (100mg/kg) ungazange ubonise ukuthuthukiswa okuphawulekayo ezinkomba zokuziphatha, kwakunomkhuba wokushintsha kwe-hypothalamic appetite ehlobene ne-gene expression ezingeni lamangqamuzana.

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Olunye ucwaningo lwendlela yamangqamuzana lubonise ukuthi i-5-HT, ngokubopha i-5-HT1B kanye ne-5-HT2C receptors ku-hypothalamic POMC, AgRP namanye ama-neuron, ivimbela ama-neurons e-AgRP/NPY akhuthaza ukudla, yenza kusebenze ama-neurons e-POMC avimbela ukudla futhi akhuthaze ukusetshenziswa kwamandla, bese idlala indima yokulawula ukudla kanye nesisindo. Lokhu kunikeza ukusekelwa okubalulekile kwamangqamuzana okuthuthukisa ukondla ngokomzwelo ngendlela ye-tryptophan-5-HT.

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Abacwaningi baphinde basebenzisa i-mouse hypothalamic neuron cell line GT1-7 ukuze baqhubeke nokuqinisekisa umphumela wokulawula we-5-HT kuma-neuropeptides ahlobene nesifiso sokudla. Baphathe amaseli e-GT1-7 ngo-10μM we-corticosterone (CORT) amahora angu-24 ukuze balingise izimo zengcindezi engapheli. Imiphumela yabonisa ukuthi ukubonakaliswa kwesifiso sokudla okuphromotha izakhi zofuzo ezifana ne-AgRP ne-OX1R kwakulawulwa kakhulu ukwelashwa kwe-CORT, kuyilapho ukubonakaliswa kwesifiso sokudla kuvimbela izakhi zofuzo ezifana ne-MC4R, 5-HT1B kanye ne-5-HT2C yayingalawulwa kahle. Ngemva kokwelashwa kusengaphambili nge-0.1μM 5-HT amahora angu-2, inkulumo engavamile ye-CORt-induced AgRP nezinye izakhi zofuzo zingahlehliswa kakhulu, futhi isisho se-MC4R, 5-HT1B kanye ne-5-HT2C singabuyiselwa. Lokhu kuphinde kwaqinisekisa umphumela oqondile wokulawula we-5-HT kuma-hypothalamic neurons.

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Isifinyezo sedatha:

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Imiphumela yokucindezeleka okungapheli ku-tryptophan metabolism homeostasis kumagundane: Ukucindezeleka okungapheli kwabangela ukuba amazinga e-serum tryptophan ehle (P

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Umthelela we-tryptophan ekufuneni ukudla kanye nokuziphatha okufana nokucindezeleka okubangelwa ukucindezeleka okungapheli: I-tryptophan supplementation ye-dose ephezulu ibuyisele ukuziphatha okungavamile kokudla kanye nokulahlekelwa kwesisindo okubangelwa ukucindezeleka okungapheli (P

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Imiphumela ye-tryptophan supplementation kuma-neurons e-hypothalamic feeding kanye nabalawuli besifiso sokudla kumagundane okucindezeleka okungapheli: I-Immunohistochemical staining ibonise ukuthi ukubonakaliswa kwe-c-fos ne-AgRP endaweni ye-ARC ye-hypothalamus eqenjini lokucindezeleka okungapheli kwanda kakhulu, kuyilapho ukubonakaliswa kwe-LEPR kwehle kakhulu (P

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Imiphumela ye-tryptophan endleleni ye-5-HT ye-metabolic ku-hypothalamus yamagundane okucindezeleka okungapheli: I-Serum tryptophan kanye namazinga we-5-HT anyuswe kakhulu ngemva kwe-tryptophan supplementation (P

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Sekukonke, lolu cwaningo luveza ukuthi ukucindezeleka okungapheli kubangela ukuphazanyiswa kwenethiwekhi yokulawula i-hypothalamic appetite ngokuphazamisa indlela ye-tryptophane-5-HT ye-metabolic, ebuye ibangele ukudla ngokomzwelo. Ukwengezwa kwe-tryptophan yangaphandle, ikakhulukazi kumithamo ephezulu (300mg/kg), kubuyisela amazinga amaphakathi we-5-HT, kusebenze i-hypothalamic 5-HT1B kanye nama-receptors angu-5-HT2C, kuvimbela ama-neurons e-AgRP/NPY, kusebenze ama-neurons e-POMC, futhi kuthuthukisa ukuphazamiseka kwemizwelo okuhlobene nokucindezeleka nokuziphatha okungavamile kokudla.

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Lo mphumela wocwaningo unokubaluleka okusebenzayo okubalulekile. Empilweni yanamuhla esheshayo, enengcindezi ephezulu, abantu abaningi babhekene nezinkinga zemizwa ezibangelwa ukucindezeleka kanye nokuphazamiseka kwesisindo. Ucwaningo luye lwabonisa ukuthi ukucindezeleka kwesikhathi eside kubangela ukuba izinga le-tryptophan lomzimba linciphe, i-5-hydroxytryptamine synthesis yehla, bese iholela ochungechungeni lwezinkinga ze-neuroendocrine, okuholela ekucindezelekeni, ukukhathazeka neminye imizwelo engalungile, kanye ne-hyperappetite, ukukhuluphala kanye nezinye izinkinga ze-metabolic. Lolu cwaningo lwembula indima eyinhloko ye-tryptophan kanye ne-metabolite yayo i-5-hydroxytryptophan ku-axis yokulawula i-stress-emotion-appetite, inikeza imibono emisha nezindlela zokukhulula ukucindezeleka nokuthuthukisa ukuphazamiseka kwemizwelo nokuphazamiseka kwesisindo.

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Ngokusekelwe kokutholakele, abacwaningi banikeza izincomo ezithile zokudla ukusiza abantu babhekane kangcono nokucindezeleka. Okokuqala, isengezo esifanele sokudla okucebile kwe-tryptophan ekudleni kwansuku zonke, njengamaqanda, ushizi, amantongomane, ubhanana, oats, njll., kungasiza ekuthuthukiseni izinga le-tryptophan emzimbeni, kukhuthaze ukuhlanganiswa kwe-5-hydroxytryptophan, ngaleyo ndlela kuthuthukise isimo somzwelo futhi kuvimbele ukudla ukucindezeleka. Kodwa-ke, kufanele kuqashelwe ukuthi i-tryptophan ekudleni ayimuncwa futhi isetshenziswe ngo-100%. Ngasikhathi sinye, ukufakwa kwethamo elikhulu lesikhathi eside se-tryptophan (okungaphezu kuka-500mg/kg) kungabangela ukulimala kwezinso. Ngakho-ke, ekulinganiseni kokudla kwansuku zonke, ukwesekwa okulinganiselwe kwe-tryptophan kungaba, ungakhuthazi ukusetshenziswa ngokweqile kwezithako ze-tryptophan.

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Ngaphezu kwalokho, ukuvivinya umzimba okusesilinganisweni njengokugijima, ukubhukuda, i-yoga, njll., nakho kungasiza ekwandiseni izinga le-tryptophan ne-serotonin synthesis emzimbeni, kukhulule ingcindezi futhi kuthuthukise isimo sengqondo. Ukulala ngokwanele, ukuba nesimo sengqondo esiqondile nesokuba nethemba, nokufunda ukuveza imizwa ngendlela enengqondo konke kuyizindlela eziphumelelayo zokubhekana nokucindezeleka. Lapho ubhekene nezinkinga ezingathi sína ezingokomzwelo ezifana nokucindezeleka nokukhathazeka, kuyadingeka ukufuna ukwelashwa kwengqondo okuqeqeshiwe kusenesikhathi.

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Ekuphetheni, lolu cwaningo lwembula indlela yokudla okungokomzwelo okubangelwa ukucindezeleka okungapheli ngokombono we-tryptophan metabolism, futhi inikeza umbono omusha wokukhulula ukucindezeleka, ukuthuthukisa ukuphazamiseka kwemizwelo kanye nokuphazamiseka kwesisindo. Nakuba ucwaningo olwengeziwe lwabantu ludingeka ukuze kwandiswe umthamo kanye nobude besikhathi se-tryptophan supplementation ekudleni, imiphumela yalolu cwaningo isinikeze imibono emisha yokuthuthukisa impilo engokomzimba nengqondo ngokulawula ukudla. Sikholelwa ukuthi ngokudla ukudla okulinganiselayo, ukuvivinya umzimba okusesilinganisweni, ukulala kahle kanye nokubhekana nesimo esingokomzwelo esihle, singabhekana ngokuzolile nokucindezela kokuphila futhi samukele ikusasa elingcono.