E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:
- Biol Psychiatry. 2013 May 1; 73 (9): 827-835.
- E hatisitsoe Inthaneteng 2013 Mar 26. doi: 10.1016 / j.biopsych.2013.01.032
PMCID: PMC3658316
NIHMSID: NIHMS461257
Rajita Sinha, PhD1,2,3 'me Ania M. Jastreboff, MD, PhD4,5
Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Biol Psychiatry
Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.
inahaneloang
Ho imeloa kelellong ho amahanngoa le botenya haholo 'me methapo ea pelo ea khatello ea kelello e fetela haholo le ea taolo ea matla a lijo le matla. Tlhahlobo ena e tla tšohla khatello ea kelello, allostasis, lefu la neurobiology ea khatello ea kelello 'me e kopane le tsamaiso ea neural ea takatso ea lijo le matla a lapeng. Ho imeloa kelellong ke ntho e ka sehloohong e kotsing ea ho tsuba le ho tsuba ho tsuba. Liphetoho tse phahameng tsa khatello ea kelello li ja mekhoa ea phepo 'me li sebelisa lijo tse ngata haholo (HP), tseo hape li eketsang matla a khothatsang a lijo tsa HP le mocheso oa allostatic. Mokhoa oa khatello ea kelello oo khatello ea kelello e amang monehelo ka oona e ka u susumetsang le ho sebelisoa ha lijo tsa HP hammoho le lithethefatsi tse lemalang. Ka matla a khothatsang a lijo tsa HP le ho ja lijo tse ngata ho feta, ho na le maemo a mangata a khatello ea maikutlo le lipotoloho tse fanang ka ts'ehetso e amanang le khatello ea kelello le HP e amanang le lijo hammoho le liphetoho tse amanang le lijo, ho akarelletsa le liphetoho tsa metabolism ea glucose, kutloisiso ea insulin, le lihomone tse ling tse amanang le matla a homeostatsis. Liphetoho tsena tsa meriana li ka boela tsa ama ts'ebetso ea dopaminergic ho susumetsa lijo le tšusumetso ea lijo tsa HP. Mohlala o kopanetsoeng o ts'oanelang ho ts'oaetsoa oo ho phetoang ho hoholo ha khatello ea kelello ho fetola phekolo ea khatello ea kelello le takatso ea lijo, matla a macha a nang le likarolo tse peli tse amanang le mekhoa ea neural e tlatsetsang khatellong ea maikutlo le lijo tse bakoang ke HP lijo tse susumetsang le ho kopanela ho ja lijo tse joalo ho ntlafatsa kotsi ea ho fumana boima ba 'mele le botenya. Litsela tsa nakong e tlang li tla fumanoa ho eketsa kutloisiso ea mekhoa eo khatello ea kelello e ka eketsang kotsi ea boima ba 'mele le botenya.
Botenya le ho lemala: karolo ea bohlokoa ea khatello ea kelello
Ho lemalla joala le lithethefatsi ho tsoela pele ho ba bothata ba bophelo bo botle ba sechaba ka liphello tse senyang tsa bongaka, tsa sechaba le tsa sechaba.1). Ho imeloa kelellong ke ntlha e kotsi ea kotsi e amang bobeli ba ts'oaetso ea lithethefatsi le ho khutlela boitšoarong bo hlephileng, ka hona ho beha koluoa le ho hlaphoheloa ho tsoa ho mafu ana (2Botenya ke lefu la seoa la lefats'e, 'me United States e ka pele ho seoa sena ka karolo ea bobeli borarong ea baahi ba eona ba khetholloang e le ba nonneng kapa ba nonneng haholo (BMI> 25kg / m)2) (3). Tsoelo-pele ea botenya le ho lemala e amana le litšobotsi tsa liphatsa tsa lefutso, tsa tikoloho le tsa batho ka bomong tseo kaofela li tlatsetsang lefung lena (4); (5). Ha litlhaloso tsa nakong e fetileng li lebisa tlhokomelo linthong tsena, pampiri ena e hlahloba karolo ea khatello ea kelello, lijo tsa lijo le tšusumetso ea lijo ka ho tlatsetsa ho ho ja haholo ka botenya.
Khatello ea kelello le allostasis
Ka ho fetisisa feela, khatello ea kelello ke ts'ebetsong eo ntho leha e le efe e thata, e ke keng ea laoloa le e sithabetsang maikutlong kapa ea 'mele kapa liketsahalo tsa liketsahalo li etsa hore ho be le mekhoa e ikamahanyang kapa ea maladaptive e hlokehang ho khutlisetsa homeostasis le / kapa botsitso (6), (2). Mehlala ea khatello ea maikutlo e kenyelletsa likhohlano tsa batho ba bang, ho lahleheloa ke kamano e nang le morero, ho hloka mosebetsi, lefu la setho sa lelapa, kapa tahlehelo ea ngoana. Lintho tse ling tse tloaelehileng tsa khatello ea kelello li kenyeletsa tlala kapa ho hloka lijo, ho hlobaela kapa ho lahleheloa ke boroko, ho kula ho tebileng, ho fetela ho feteletseng kapa hypothermia, liphello tse mpe tsa lithethefatsi le ho tlosa lithethefatsi. Ho ikamahanya le khatello ea maikutlo ho amana le maikutlo a allostasis, e leng bokhoni ba ho finyella botsitso ba 'mele ka phetoho ea sechaba sa ka hare le ho boloka botsitso bo hlakileng boemong bo bocha ba' mele (6); (7)). Ho ea ka McEwen le basebetsi-'moho le eena, ho na le liphetoho tse tsoelang pele tsa sechaba sa ka hare, ho feto-fetoha ha maemo a bophelo, mehopolo, le mesebetsi e le batho ka bomong ba arabelang le ho fetola litlhoko tsa tikoloho (7). Ho imeloa kelellong ho feteletseng, ho thoeng ke ho eketseha boima bo tsitsitseng, ho fella ka "ho roala le ho senya" mekhoa ea tsamaiso ea phetoho e bakoang ke liphetoho tsa likokoana-hloko tse fokolisang mekhoa ea ho fetola khatello ea kelello le ho eketsa ts'oaetso ea mafu (7). Ka hona, maemo a mangata a khatello e ke keng ea laoloa le maemo a ho imeloa kelellong le a sa foleng a etsa hore ho be le moroalo o tsitsitseng o fokolang o etsang hore ho be le mebuso e meholo ea metsoli le ea boits'oaro e tlatsetsang malapaptive boitšoaro le boipheliso ka ntle ho homeostatic range {McEwen, 2007 #4}.
Ho imeloa kelellong, tsietsi e sa feleng, le ho eketseha ha kotsing ea ho ba botenya
Ho tšoana le liphello tsa ho imeloa kelellong khafetsa le ho sa foleng ka ho eketseha ho lemalla ho lemala (2), bopaki bo bongata bo fumanoang liphuputsong tsa batho le litsebi tsa bongaka bo bontša hore mokhatlo oa bohlokoa le o motle oa liketsahalo tse sithabetsang tse sa laoleheng le khatello ea kelello e sa feleng e bolela ka botebo, BMI le phaello ea boima (8), (9), (10), (11). Kamano ena e boetse e bonahala e le matla ka ho fetisisa har'a batho ba nang le boima bo feteletseng le ba tsitsitseng ho ja (8), (9), (12). Ho sebelisa tlhahlobo e felletseng ea lipuisano ea khatello ea maikutlo le ho pheta-pheta khatello ea maikutlo meleng ea batho ba baholo ba phetseng hantle (n = 588), re fumane hore matšoao a phahameng a liketsahalo tse sithabetsang le likhatello tse sa feleng (bona Lethathamo 1) ho feta bophelo bohle bo ne bo amahanngoa le tšebeliso e feteletseng ea joala, ho tsuba le BMI e phahameng, ka mor'a ho laola lilemo, morabe, tekano le maemo a maemo a maemo a bophelo (bona Setšoantšo sa 1).
Ha khatello ea kelello e theola boima ba 'mele le BMI, re boetse re hlahloba liphello tsa eona ka basalluse ea basal, insulin le ho hanyetsa insulin. Tlhahlobo ea hoseng ea ho ja lijo tsa mali ea mali (FPG) le "insulin" e ile ea hlahlojoa ka bongata sehlopheng se seholo sa baithaopi ba nang le bophelo bo botle le tlhahlobo ea li-homeostasis (HOMA-IR) e baloang e le letšoao la insulin ho hanyetsa. Re fumane hore ho imeloa kelellong ho amanang le liphetoho tse amanang le BMI liemong tse phahameng tsa tsoekere, insulin le HOMA-IR (Setšoantšo sa 2). Lintlha tsena li bonts'a mekhatlo e matla e pakeng tsa khatello ea kelello e kenyelletsoang le ho se sebetse ha metso ho batho ba phahameng ho bapisoa le lihlopha tse tlaase tsa BMI. Liphuputso tsena li tšoana le lipatlisiso tsa nakong e fetileng tse bontšang liphello tse matla tsa khatello ea kelello ho eketsehileng tšebeliso ea lithethefatsi ho batho ba tloaelehileng ho ba boima ha ba bapisoa le basebetsi ba khanyang kapa ba khathollang (2). Ka kakaretso, liphuputso tsena li bontša hore ho imeloa kelellong le ho imeloa kelellong ho eketsa kotsi ea botenya le hore batho ba nang le li-BMIs tse phahameng ba ka ba kotsing ea ho ja lijo tse amanang le khatello ea kelello le phaello e latelang ea boima.
Matšoenyeho le mekhoa ea ho ja
Ho imeloa kelellong ho matla ho fetola ho ja (13); (10); (9). Le hoja lipatlisiso tse ling li bontša ho fokotseha ha lijo tse kenang ka tlas'a khatello ea maikutlo, khatello ea kelello e matla e ka boela ea eketsa ho ja, haholo ha HP, lijo tse nang le lik'halori li fumaneha (9, 13), (14), (15), (16). Ka mohlala, ka tlaleho ea boinotšing feela, 42% ea liithuti e tlalehile ho eketseha ha lijo le ho imeloa kelellong, 'me 73% ea barupeluoa ba tlalehile keketseho ea ho noa lijo nakong ea khatello ea kelello (17). E 'ngoe ea boraro ho halofo ea lipatlisiso tsa liphoofolo kapa tsa batho ba laboratori li bontša ho eketseha ha lijo nakong ea khatello ea maikutlo, ha tse ling li sa bontše phetoho kapa ho fokotsa ho ja (18), (11). Ka hona, le hoja ho eketseha ha lijo le ho imeloa kelellong ha ho hlahe ho bohle, ka sebele ho ama batho ba bangata. Ho phaella moo, ke habohlokoa ho hlokomela hore lintlha tse 'maloa tsa liteko li ka kenya letsoho ho etsa lipatlisiso ka liphetoho tsena tse fapaneng ka ho ja ho bakoang ke khatello ea kelello (19), (20), (12). Lintlha tsena li kenyelletsa mofuta o tobileng oa khatello ea maikutlo o sebelisetsoang ho sebetsana le khatello ea kelello, bolelele ba khatello ea khatello ea kelello, nako e telele ea ho pepeseha lijo le palo le mofuta oa lijo tse fanoang tekong, hammoho le litekanyetso tsa satiety le tlala qalong ea phapusi ea ho bala. Lintho tsena li ka tlatsetsa ho fapaneng liphellong tsa liteko tsa laboratori tse nang le liphello tsa khatello ea kelello litabeng tsa lijo.
Ho na le bopaki ba bohlokoa bo bontšang hore ho ka ba le liphello tse kotsi tse bakoang ke khatello ea kelello ea lijo (mohlala, ho qeta ho ja, ho thibela ho noa, ho betha) le lijo tsa lijo (10). Ho imeloa kelellong ho ka eketsa ho sebelisoa ha lijo tse potlakileng21), lijo tse monateloang (22), lijo tse nang le lik'halori-tse teteaneng le tse ratoang haholo (23), 'me khatello ea kelello e amana le ho ja ho ja lijo tse ngata (12). Liphello tsa khatello ea kelello e ka ba tse fapaneng ha li bapisoa le batho ba feteletseng (8, 24-26). Ho fumanoe hore ho ja lijo tse imetsoeng ke khatello ea kelello ho basali ba mahlomoleng empa ho ja lijo tse imetsoeng ke khatello ea kelello ho bonahala ho e-na le phello e sa lumellaneng ea lijo ho batho ba itšoereng hantle (24). Ho feta moo, liphetoho tsa ho ja li ka 'na tsa ama metabolism ea lik'habohaedreite le kutloisiso ea insulin (27). Basali ba phetseng hantle, ho itlopa joala ho eketsa khase ea khase, karabo ea insulin, le ho fetola mokhoa oa ho thibela leptin (28). Ho fumanoe makhetlo a sa tloaelehang a lijo ho eketsa insulin ho arabela tlhahlobo ea tlhahlobo ka mor'a nako ea lijo tse sa tloaelehang (27). Lipatlisiso tsena li bontša hore khatello ea kelello e ka khothalletsa mokhoa o sa tloaelehang oa ho ja le ho fetola khetho ea lijo le hore ho feteletsa ho feta 'mele le batho ba feteletseng ba ka' na ba e-ba kotsing ea ho ba le liphello tse joalo, mohlomong ka liphetoho tse amanang le boima ba molao tsamaiso ea matla le homeostasis.
Ho ba le methapo ea kutlo ea kelello ea khatello ea kelello le matla a maholo a lapeng
Mokhoa oa ho sebetsana le khatello ea kelello e matla ho bonahala ka litsela tse peli tse amanang le khatello ea kelello. Lekhetlo le le leng ke motsoako oa hypothalamic-pituitary-adrenal (HPA), oo motsoako oa corticotropin-release (CRF) o lokolloang ho tloha ho "core" (PVN) ea hypothalamus, e tsosang sephiri sa adrenocorticotrophin hormone (ACTH) ho tswa ho anterior pituitary, e leng e ntan'o susumelletsa ho khutsuoa ha glucocorticoids (GC) (cortisol kapa corticosterone) ho tswa ho litšoelesa tsa adrenal. Ea bobeli ke tsamaiso ea methapo ea boithaopo, e tsamaisoang ke meriana ea sympathoadrenal (SAM) le tsamaiso ea parasympathetic. Likarolo tse peli tsa litsela tsena tsa khatello ea kelello li boetse li susumetsa li-cytokine tse chesang le ho itšireletsa mafung (2); (6).
Ho lokolloa ha CRF le ACTH ho tloha hypothalamus le anterior pituitary nakong ea khatello ea kelello ho fella ka ho lokolloa ha GC ho tloha adrenal cortex, e leng eona e tšehetsang matla a ho matlafatsa matla a motlakase le gluconeogenesis. Tšusumetso e nang le kutloelo-bohloko e amanang le khatello ea kelello e eketsa khatello ea mali le ho fapanyetsana ha mali ho tsoa pampiring ea moriana ho ea ho mesifa ea masapo le boko. Liphello tse bohloko tsa khatello ea kelello ea CRF le ACTH li felisoa ke maikutlo a mabe a GC, a tšehetsa ho khutlela homeostasis, le tlas'a maemo a joalo a khatello ea kelello, ho na le bopaki bo bongata ba hore ho fokotseha ho e-na le ho eketseha ha lijo (19), (9). Hypothalamus e arabela ho li-GC ka melaetsa e mebe, empa hape le insulin, e tsejoeng ho tsoa liphakeng 'me e kopane le tsoekere ea metabolism le polokelo ea matla (29), (9), le li-hormone tse ling, joaloka leptin e thibelang takatso ea lijo, le ghrelin e khothalletsang takatso ea lijo (5); (9); Currie, 2005). Li-glucocorticoids li eketsa leptin ea plasma le maemo a ghrelin, 'me ghrelin e boetse e eketseha ka khatello ea maikutlo' me e ameha ho laola matšoenyeho le maikutlo (30). Ho feta moo, li-neuropeptide tse ngata tsa hypothalamic, tse kang CRF, propriomelanocortin (POMC), Y (NPY) ea methapo ea orexigen, le peptide e amanang le agouti (AgRP), hammoho le batho ba amohelang melanocortin ba amehang ho laola khatello ea maikutlo, ba boetse ba bapala karolo ea ho fepa (31). Li-glucocorticoids li fetola polelo ea li-neuropeptides tse laolang matla a ho kenngoa ha matla (32), (31). Ka mohlala, li-adrenalecom tse kopanetsoeng li fokotsa ho ja lijo, 'me tsamaiso ea GC e eketsa lijo tsa lijo ka ho susumelletsa ho lokolloa ha NPY le ho thibela ho tlosoa ha CRF (31). Ho feta moo, thibelo ea lijo le lijo tse phahameng tsa mafura li fetola likarabo tsa HPAaxis khatellong ea maikutlo le GC ea liphatsa tsa lefutso sebakeng se seng sa boko bo amehang ho homeostasis le khatello ea matla (33), (20), (18), (34), (35). Ka lebaka leo, hypothalamus ke sebaka se boima mosebetsing oa potoloho hammoho le taolo ea phepo le matla a tekanyo.
Matšoao a sa feleng le a phahameng a khatello ea kelello e sa phekoleheng a fella ka ho senyeha ha motsoako oa HPA, ka liphetoho ho hlahisa liphatsa tsa lefutso tsa GC (6), (36), e leng eona, e boetse e ama matla a homeostasis le mokhoa oa ho fepa. Ho sebetsa ha nako e sa lekanyetsoang ha axisisi ea HPA ho tsebahala ho fetola methapo ea methapole le ho khothalletsa ho thibela insulin, ka liphetoho tse ngata tse amanang le takatso ea lijo (mohlala, leptin, ghrelin) le ho fepa li-neuropeptides (mohlala, NPY) (37), (38), (39), (40). Ho imeloa kelellong ho sa khaotse ho eketsa li-GC, mme ho khothalletsa mafura a mpa, moo ho nang le insulin, e fokotsa mosebetsi oa axisisi oa HPA (9), (38) (33). Liphuputso tsa motheo tsa saense li bontšitse hore adrenal steroids e eketsa tsoekere le mahlaseli a insulin hammoho le khetho le ho ja lijo tse phahameng tsa caloric (13), (14), (15), (41). Li-GC tse phahameng le ho eketseha ha insulin li na le liphello tse ts'oanang le ho feta ha ho eketseha ha lijo tsa HP lijo le mafura a mpa (23), (9); (42). Matšoao a phahameng a khatello ea makhetlo a mangata a boetse a etsa hore motho a se ke a hlola a e-ba le kutloelo-bohloko, 'me ho eketseha ha khatello ea kelello litabeng tsa boipheliso ho amana le litekanyetso tsa insulin le ho hanyetsa insulin ho bacha le batho ba baholo (43).
Liphello tsa khatello ea kelello lijong tsa lijo, tšusumetso le ho ja
Li-circuit cirpotits tsa hypothalamic li tlas'a taolo ea litsela tsa extrahypothalamic cortico-limbic modulated ke CRF, NPY le litsela tsa noradrenergic. Khatello ea khatello ea maikutlo e qalisoa ka tsela ea amygdala le taolo ea khatello ea kelello e hlaha ka tsela e fokolang ea GC ho hippocampus le libaka tsa mediater prefrontal cortical (mPFC)6). Litlhahiso tsa extrahypothalamic tsa CRF li ameha ka likarabo tse ikhethang le tsa boitšoaro tsa khatello ea kelello, ha ho lokolloa ha NPY orexigenic nakong ea khatello le ho eketsa NPY mRNA mokokotlong oa arpothalamus oa hypothalamus, amygdala le hippocampus, ho eketsa phepo, empa hape ho fokotsa ho tšoenyeha le khatello ea maikutlo (31). Ho imeloa kelellong le li-GC tse ka fetisetsang phetiso ea dopaminergic le ho fumana moputso oa ho fumana moputso le ho kenella liphoofolong tsa laboratori (18), (13) (2). Ho imeloa kelellong ho eketsa ho fumana lijo, ho ja lijo tse phahameng tsa mafura (11), (16), le lijo tse qobelloang ho batla lijo tsa HP (25), le ho khothalletsa mekhoa e itšetlehileng ka moputso (44). Ho imeloa kelellong ho ka 'na ha etsa hore motho a lakatse lijo tse nang le lijo tse nooang, lijo tse hlahisang lijo le lijo tse phahameng tsa HP tse kenang ho batho ba nang le boima bo feteletseng ba batho ba itekanetseng (25).
Ho noa lithethefatsi tse eketsehileng le ho ja lijo tse phahameng ho fetola li-CRF, GC le mesebetsi ea noradrenergic ho eketsa ho matlafatsa litsela tsa meputso (ho kenyeletsa sebaka sa ventral tegmental [VTA], nucleus accumbens [NAc], dorsal striatum le libaka tsa mPFC) tse susumetsang lisebelisoa tsa lithethefatsi le HP lijo le ho eketsa takatso ea lithethefatsi / lijo le ho ja (45), (2), (46). Habohlokoa le ho feta, potoloho ena e susumetsang e feta ka libaka tsa maoto le maikutlo (mohlala, amygdala, hippocampus le insula) e etsang karolo ea ho ba le maikutlo le khatello ea kelello, le ka mekhoa ea ho ithuta le ea mohopolo e amehang tabeng ea ho buisana ka boitšoaro le likamano tsa maikutlo tse hlokang ho fetoha homeostasis (2); (47). Ka mohlala, amygdala, hippocampus le insula li phetha karolo ea bohlokoa ho ngoliseng meputso, thuto le mekhoa e fumanoang molemong oa meputso bakeng sa ho ba le maikutlo a holimo maikutlong le moputso le boikutlo bo ka 'nang ba e-ba teng le ho fana ka moputso oa lijo-thollo (48), (49). Ka lehlakoreng le leng, likaroloana tsa mefuta-futa ea li-prefrontal cortex (PFC) li kenngoa mesebetsing e phahameng ea tsebo le ho laola le ho laola maikutlo, likarabo tsa 'mele, maikutlo, litakatso le takatso (50). Ho imeloa kelellong le ho pheta-pheta ho fetola likarabo tsa moralo le tse sebetsang likarolong tsena tsa bokooa le limbic, ho fana ka motheo oa liphello tsa khatello e sa foleng libakeng tsa cortico-limbic tse fokolang lijo le moputso (51); (52). Liphuputso tsena li lumellana le lipatlisiso tsa boitšoaro le tsa bongaka tse bontšang hore khatello ea maikutlo kapa tšusumetso e mpe e fokotsa ho laola maikutlo, maikutlo a maholo le a boitšoaro, ho eketsa ts'oaetso (2) eo hape, e amanang le ho kopanela ho hoholo ts'ebetsong joala, ho tsuba, le tšebeliso e mpe ea lithethefatsi hammoho le ho ja ho eketsehileng ha lijo tsa HP (23); (53); (54). Ha u ntse u tsepamisa kelello tabeng ea ho lemalla lijo le kamoo ho labalabela lipompong le mafura ho ka eketsang botenya haholo (55), ho tla ba bohlokoa ho nahana hore na ts'oaetsano ea ho lemalla lijo e boetse e mpefalitsoe ke khatello ea kelello e sa foleng.
Lijo tsa lijo, moputso oa lijo, tšusumetso le ho ja
Li-cue tsa lijo tse hlakileng haholo li tloaelehile tikolohong ea hona joale ea botenya. Ho ipapisa le li-cue tsena tsa lijo tsa HP ho ka eketsa ho ja lijo le ho tlatsetsa ho boima ba 'mele (49). Lijo tse joalo li khotsofatsa, li susumelletsa boko ho putsa litsela, 'me, ka mekhoa ea ho ithuta / maemo, ho eketsa monyetla oa ho ja lijo tsa HP le ho li sebelisa (56), (57), (58). Liphoofolo le batho ba ka ba boemong ba ho batla lijo le ho ja lijo tsena tsa HP, haholo-holo mohoong oa litlhahiso kapa 'cues' tse amanang le lijo tsa HP tse tikolohong (55), (59), (57). Keketseho e joalo ea maemo le lipapali tse amanang le ho eketsa ho kenngoa ha lijo tsa HP li etsa hore ho be le mekhoa e metle ea litsela tsa boipheliso, e leng se etsahalang ka ho eketseha ha lijo tsa HP tsena, 'me ho etsa hore ho be le ho "batla" le ho batla lijo tsa HP, tse tšoanang le ts'ebetso ea ts'ireletso e hlahang ka ho eketsa ho noa joala le lithethefatsi (60). Lipatlisiso tse ngata tsa liphoofolo le lipatlisiso tse ntseng li hōla tsa batho ba nang le neuroimaging hona joale li bontša ka ho hlaka hore liphallelo tsa bokooa li na le mekhoa e mengata le ho eketsa phetiso ea dopaminergic le tlhahiso ea lijo ea HP, e nang le ho eketseha ha lijo le ho susumetsa lijo (61), (62), (63), le ho feta boikarabello ba boko ba libaka libaka le ho lakatsa lijo har'a batho ba nang le BMI e phahameng (64), (65), (66), (67).
Ha ho sebelisoa haholo lijo tsa HP, liphetoho tse nang le lik'habohaedreite le mafura a metabolism, kutloisiso ea insulin le li-hormone tsa lijo tse fetolang matla a lehae a homeostasis li boetse li susumetsa meputso ea li-neural libaka tse amehang ka ho eketseha ha mahlahahlaha, ho batla le ho susumetsa lijo (68), (57), (69), (70), (71), (72), (73). Ho etsa mohlala, batho ba phetseng hantle ba nang le phepo ea phepo ea mali ea mali ea plasma ba etsa hore ho be le khutso ea insulin, e leng ho nolofalletsang likokoana-hloko hore li hlahise liphatsa tsa lefutso; ho thahasellisang ho kenngoa ha insulin e 'nile ea bontšoa ho thibela takatso ea lijo le ho fepa (74); (75); (76); (77); (78). Leha ho le joalo, boemong bo phahameng bo sa foleng ba insulin le ho hanyetsa insulin, joalokaha ho hlokomeloa ho batho ba bangata ba nang le botenya, ba ka khothalletsa lijo le ho ja lijo hape ba fetola mesebetsi ea dopaminergic libakeng tsa moputso tse kang VTA, NAc le dorsal striatum (78), (79), (80), (81). Ka mokhoa o ts'oanang, leptin le ghrelin li susumetsa phetiso ea dopaminergic liphuthehong tsa moputso oa boko le ho batla boitšoaro ho liphoofolo, le ho etsa hore batho ba fumane meputso ea bokooa (69), (70), (71), (73). Ho hanyetsa insulin le T2DM li boetse li amahanngoa le liphetoho mosebetsing oa lipotoloho tsa moputso oa mongobo le karabo ea bona ho lijo tsa lijo (82), (79), (80). Re sa tsoa bontša ho eketseha ha limbic le ho hlasela habonolo ho khatello ea kelello le lijo tse ngata ho feta batho ba omeletseng (81) (bona Setšoantšo sa 3). Ho feta moo, mosebetsi o phahameng oa insulin le dorsal striatum o amana le litekanyetso tse phahameng tsa insulin, ts'oaetso ea insulin le ka takatso ea lijo ha barupeluoa ba pepesehela maemo a lijo tse ratang haholo (81). Ka kakaretso, liphuputso tsena li tšehetsa khopolo ea hore ho ka ba le liphetoho tse amanang le tse amanang le liketsahalo tsa motlakase le tsa mahlaseli a nang le tšusumetso e kopanelang haholo ho ama tlala, ho khetha lijo le khethollo, ho susumetsa lijo tsa HP le ho ja lijo tse ngata tsa HP.
Bopaki bo ntseng bo eketseha bo fana ka maikutlo a hore li-hormone tse amehang takatsong ea lijo le matla a maholo (mohlala, leptin, ghrelin, insulin) li ka boetse tsa phetha karolo ea ho lakatsa, ho fumana moputso le ho batla ho qobella joala le lithethefatsi (49); (57); (58); (68); (69); (72); (71) Mekhatlo ena e entse hore ho be le thahasello ho hlahloba khopolo ea "ho fetisetsa lithethefatsi", kapa ho nkela "ho lemalla" ho hong, tabeng ena lijo tse itseng, tse ling tse kang joala kapa lintho tse ling (83). Ka mohlala, phuputso ea morao-rao e fumane hore tšebeliso ea joala e eketsehile ka mor'a ho lahleheloa ke boima ba 'mele bo potlakileng, bo boima joalokaha ho bonahala ho bakuli ba etsoang opereishene ea bariatric (84). Ka hona, lipatlisiso tsa nakong e tlang mabapi le ho khoneha ho matlafatsa lijo le lithethefatsi tse lemalang batho ba tlokotsing li ka fana ka leseli ka lits'ebetso tse hlahisang liketsahalo tsena.
Boikoetliso ba 'mele le metsoako ea khatello ea kelello: tšusumetso ea ho lakatsa lijo le ho ja
Ho eketsa litekanyo tsa boima ka holimo ho mekhoa e metle ea bophelo bo botle le ho ja lijo tse ngata tsa HP, ho tlisa liphetoho meleng ea metabolism, insulin kutloisiso le lihomone, ho laola takatso ea lijo le matla a maholo a matla (85), (57), (58). Joalokaha ho bontšitsoe likarolong tse fetileng, lintlha tsena tsa ts'ebetsong ha li susumetse feela litlhoko tsa mahlaseli a marang-rang ho ama tšusumetso, empa li boetse li ama lipotoloho tsa hypothalamic, ho sebelisana le khatello ea kelello e holimo le matla a tsamaiso ea matla a tsamaiso. Kahoo, ha ho makatse hore ebe boima bo eketsehileng, insulin ho hanyetsa le ho ja lijo tse phahameng li amahanngoa le likarabo tse fokolang tsa GC ho li sithabetsang le ho fetoloa likarabo tsa li-catecholamine tse ikemetseng le tse ling tsa limela (43), (20), (33) (34). Joalokaha ho boletsoe pejana, likarolo tse phahameng tsa khatello ea kelello le li-glucocorticoids li eketsa tsoekere le likokoana-hloko tsa insulin hape li khothalletsa hore motho a se ke a ts'oaetsoa ke insulin. Ka mokhoa o ts'oanang, likokoana-hloko tse sa foleng tsa insulin li bontšitsoe ho fokotsa likarabo tsa li-HPA le ho eketsa moelelo o bonolo oa kutloelo-bohloko (43), (86), (42), (87). Ho phaella moo, bopaki bo bontša hore khatello ea kelello e ama maemo a tsoekere le mefuta e fapaneng ho bakuli ba nang le mofuta oa 1 le 2 lefu la tsoekere (88), (89), (90), ha ghrelin, e leng ka tsela e bontšang litsela tse fanang ka moputso e khothalletsa takatso ea lijo le ho fepa (71), e boetse e ameha ka moputso o bakoang ke khatello ea kelello le ho batla lijo (30) (73). Ka hona, liphetoho tse amanang le boima ba motlakase ka lintlha tse behiloeng li ka 'na tsa eketsa mojaro o feteletseng oa boipelaetso ka ho eketseha ha molumo oa molumo oa boipheliso le ho fetola mesebetsi ea axisisi ea HPA (18), (91), (40), (6).
Tumellanong le mosebetsi ona oa pele o bontšang BMI le khatello ea kelello e amang lijo le moputso, re sa tsoa bontša hore khatello ea kelello e matla e eketsa ts'ebetso ea amygdala le karabo ea orbito-frontal cortex e fokolang ka lebese la milkshake khahlanong le kamohelo e sa pheleng, empa phello ena e ne e lekantsoe ke maemo a phahameng a cortisol le ka BMI e holimo (92). Re boetse re bontša hore ho na le boikokobetso ba hypoglycemia bo ka etsang hore ho be le meputso ea boko le limbic (hypothalamus, striatum, amygdala, hippocampus le insula), ka mokhoa o khethehileng oa lijo tsa HP, e leng se amanang le likarolo tsa cortisol tse ntseng li eketseha, ha li ntse li fokotseha ts'ebetso, phello e amanang le lebelo la tsoekere (93). Ha hypoglycemia e bonolo e ka nkoa e le khatello ea kelello ea meleng, liphihlelo tsa rona li bontša hore tšebeliso ea li-glucose e ka hlaha ka tsela e fapaneng bokong le ho imeloa kelellong, ka lebaka la ho susumetsoa ke matla le pontšo ea matsoho ka pel'a majoe a lijo empa ho fokotseha ha mongobo oa boits'oaro le mekhoa ea boipheliso . Ho feta moo, mekhoa ena ea neural e ne e le e tsotehang ho batho ba nang le bokooa ba phetseng hantle ba fanang ka maikutlo a hore liphetoho tse joalo li etsahala ka boima ba 'mele, mohlomong ho beha tsela ea boikokobetso bo amanang le boima bo amanang le boima bo amanang le khatello ea HP. Phuputso ena e kopantsoe le bopaki bo qotsitsoeng pejana e fana ka ts'ehetso e tsotehang ea neuroendocrine-metabolism-reward which e tlas'a maemo a tloaelehileng a bophelo bo botle, e hokahanya maemo a bophelo le a kelello a ho fepa le matla a homeostasis, empa ka maemo a eketsehileng a kotsi le ho ikamahanya le litsela tsena, lipotoloho tsa tsamaiso ea mekhoa ena e ka 'na ea "tlatlapuoa", e leng ho khothalletsang ho eketseha ha lijo tsa HP lijo le ho ja.
Kakaretso le mekhoa e khethiloeng
Litsela tse fanang ka bopaki tse hlahisitsoeng li fana ka maikutlo a hore mangata a mangata a lijo tsa HP le maemo a phahameng a khatello ea kelello a ka fetola boitšoaro ba 'mele' me a ama litsela tsa boko / litsela tse amehang tabeng ea ho batla le ho batla lijo tsa HP. Likarabo tse joalo tsa boitšoaro li ka ntlafatsa ntlafatso ea boima ba 'mele le mafura a' mele. Bopaki bo ntseng bo eketseha bo tšehetsa mekhoa e amanang le boima ba lik'hemik'hale tsa boitšoaro ha ho sebelisoa metsolic, neuroendocrine le li-neural (cortico-limbic-striatal), ho etsa hore lijo le lijo li be teng tlas'a maemo a lijo tsa HP le tse ling tse amanang le khatello ea kelello. Ka lebaka leo, ho na le mokhoa o motle oa hore na lijo tsa HP, lijo tsa lijo le khatello ea khatello ea kelello li ka fetola tsela efe ea boipheliso, ea khatello ea kelello le ea boipheliso bokong le 'meleng ho ntšetsa pele tlhahiso ea lijo tsa HP le ho ja (bona Setšoantšo sa 4). Joalokaha ho hlalositsoe likarolong tse fetileng, li-hormone tse amohelang khatello ea kelello (CRF, GCs) le lisosa tsa motsoako (insulin, ghrelin, leptin) ka bobeli li susumetsa phetoho ea boko bo fetotsoeng, le maemo a amanang le boima ba 'mele (liphetoho tse sa foleng), lintlha tsena li ka khothalletsa maemo a phahameng a HP tšusumetso ea lijo le phepo, ka bokhoni ba mosebetsi oa moputso oa boko. Kahoo, a ts'ebetso ea ho fepa lijo e ka 'na ea etsoa hore ho na le mekhoa e amanang le boima ba metsoako ea metsolic, neuroendocrine le cortico-limbic e tsoelang pele e khothalletsang HP lijo ho susumetsa batho le ho ja lijo tse kotsing. Ts'ebetso e joalo ea ts'ehetso e ntseng e eketseha khafetsa ea lijo tsa HP le ts'ehetso ea lijo, e tla boela e khothalletse phaello ea boima bo tlang, e leng se ka khonang ho potoloha ha maemo a amanang le boima ba 'mele ka khatello ea maikutlo le mekhoa ea metsolico, le ho eketsa ts'ehetso ea bokooa litsela tse amanang le lijo tsa HP lits'ebeletso kapa khatello ea kelello, ho khothalletsa HP lijo motsoako le ho ja. Ho phaella boima ba 'mele le BMI, ho fapana ha liphatsa tsa lefutso le motho ka bomong ho fetela ho tlōla, ho ja mekhoa ea ho itšireletsa, insulin ho hanyetsa, khatello e sa foleng, le mefuta e meng ea kelello ho ka ntlafatsa ts'ebetso ena.
Litsela tsa nakong e tlang
Le ha ho ntse ho e-na le tlhokomelo ea saense e ntseng e hōla ka litšebelisano tse rarahaneng pakeng tsa khatello ea kelello, matla a ho leka-lekanya, melao ea phepo ea lijo, le moputso oa lijo le tšusumetso le liphello tsa bona lefats'eng la botenya haholo, ho na le likheo tse kholo kutloisisong ea rona ea likamano tsena. Lipotso tse 'maloa tsa bohlokoa li ntse li sa arajoe. Ka mohlala, ha ho tsejoe hore na liphetoho tse amanang le khatello ea kelello ka cortisol, ghrelin, insulin le leptin, li susumetsa khatello ea HP lijo le ho ja. Haeba ho imeloa kelellong ho fokolisa likarabo tsa li-axis tsa HPA, joalokaha ho bontšoa lipatlisisong tse fetileng, liphetoho tsee li ama tšusumetso ea lijo le ho ja joang? Ho tla ba molemo ho hlahloba haeba liphetoho tse amanang le boima ba khatello ea kelello, li-neuroendocrine le likarabo tsa lik'hemik'hale li fetola HP lijo tse susumetsang le ho ja, le hore na liphetoho tse joalo li bolela esale pele hore na boima ba 'mele bo tla ba joang le ho nona haholo. Ho khetholla lits'ebetso tse khethehileng le ho ntlafatsa mehato ea ho hlahloba ho feto-fetoha ha maemo a amanang le khatello ea kelello le ho lemalla lijo ho ka thusa ho tataisa tlhokomelo e nepahetseng ea tlhokomelo ea meriana hammoho le ho lebisa tlhokomelo ea likarolo tse itseng tse ts'oaetsanoang tsa bophelo bo botle ba sechaba. Ho phaella moo, bopaki ba liphetoho tse sa tšoaneng tse etsahalang ka khatello ea kelello le mekhoa ea metsoako ha li bua ka lijo tse mafura haholo, le khatello ea kelello e sa foleng, le hore na li amahanngoa joang le ho ja lijo le ho fumana boima ba 'mele, e tla ba ntho ea bohlokoa ho utloisisa karolo e hatellang le ho feto-fetoha ha metsoako ka tšusumetso ea lijo, ho ja haholo le ho fumana boima ba 'mele.
Hape ho na le bobebe ba dintlha ka mekhoa e ka etsang hore ho se ke ha e-ba le boima ba 'mele kapa ho khutla ha lijo tsa HP le ho fumana boima ba' mele, 'me ho na le phekolo e matla ka ho fetisisa bakeng sa sehlopha se seng sa batho. Sebaka sa ho lemalla lithethefatsi se fana ka lintlha tsa bohlokoa ho feto-fetoha ha neurobiological tse khothalletsang ho lemalla ho tsuba le ho hlōleha kalafo. Ha ho hlōleha ho boloka boima ba 'mele ho buisitsoe ka taba ea ho khutlela maladaptive boitšoaro (94, 95), ho ka etsahala hore mekhoa e tšoanang e ka 'na ea khanna ho ja lijo tse ngata tsa HP le ho fumana boima ba' mele, empa lithuto tse tobileng tabeng ena ha li fumanehe. Hape ho na le boitsebiso bo bongata ba liphetoho tsa metsolico le liphello tsa bona tse amanang le moputso le khatello ea kelello ea methapo ea pelo e ka 'nang ea e-ba le mefuta e sa tšoaneng ea boima bo boima, ho kenyeletsa ho lahleheloa ke boima ba' mele, ho lahleheloa ke boima ba 'mele kapele ka "lijo tse senyehileng", kapa mekhoa e sa tšoaneng ea ho buuoa ka bariatric . Ho phaella moo, mafu a mangata a amanang le khatello ea kelello, a kang ho feto-fetoha ha maikutlo le ho tšoenyeha, a amahanngoa le botenya le T2DM, 'me ho thahasellisang, meriana ea maemo a joalo (ke hore ho na le batho ba nang le bothata ba ho imeloa kelellong) ho eketsa kotsi ea ho fumana boima ba' mele, empa ho na le bopaki bo fokolang ba ho hlaka mekhoa ea motheo ea liketsahalo tsena. Boemong ba T2DM, taolo e matla ea glycemic le phekolo e ngata ea insulin hangata e khothalletsa boima ba 'mele. Ha hyperinsulinemia, insulin ho hanyetsa, kapa liphello tsa nako e telele tsa insulin ho hanyetsa li ka 'na tsa e-ba le tšusumetso-ho fumana meputso e nang le mekhoa e metle le ho lakatsa lijo ho batho ba bangata, ba sa hanyetseng insulin, ho tla ba molemo ho etsa lipatlisiso tsa mekhoa ea phekolo e ka' nang ea se ke ea khothalletsa HP lijo ho lakatsa le ho noa ho fokotsa boima bo eketsehileng ho batho bana ba kotsing.
Qetellong, ho na le khatelo-pele e ncha tabeng ea boits'oaro le bo-pharmacologic tsamaiso ea botenya empa ha e tsebe hantle kamoo li amanang le khatello ea kelello, khatello ea metabo le moputso ho batho ba kotsing. Ka mohlala, bopaki ba morao-rao bo bontša hore ho boima boima ho amana le khatello e tlase ea khatello ea kelello le bokhoni bo molemo ba ho sebetsana le khatello ea kelello96); (97). Ha khatello ea kelello e khothalletsa lijo le ho ja lijo tsa ho itlopa joala, mehato ea ho fokotsa khatello ea kelello e ka ba molemo mefuteng e sebetsang ea ho laola boima ba 'mele, le lithuto tse ling tsa ho fokotsa khatello ea kelello ea ho itšoara ka matla le T2DM li bontša liphello tse ntle ho ntlafatsang khatello ea kelello, takatso ea lijo le mosebetsi oa physiologic (98, 99). Leha ho le joalo, lipatlisiso tse joalo li sa le monyenyane 'me li hloka tlhokomelo e kholo nakong e tlang. Hape, meriana e sebelisoang ho sebelisa lithethefatsi hampe le eona e nkoa e le mehato e ka khonehang bakeng sa tahlehelo ea boima ba 'mele (100). Ha e le hantle, lipatlisiso tsa nakong e tlang bakeng sa ho eketsa kutloisiso ea rona ea mekhoa ea methapo ea boitšoaro e bakoang ke khatello ea kelello, lithethefatsi le botenya e tla ba melemo e kholo ho nts'etsopele ea phekolo ea morao-rao ho thibela khaolo ea lijo tsa HP, ho ja le ho fumana boima ba 'mele.
lumela hore baa fokola
Mosebetsi ona o ne o tšehetsoa ke NIDDK / NIH, 1K12DK094714-01, le Mokhoa oa Tsela oa NIH bakeng sa Lipatlisiso tsa Lipatlisiso tsa Lichelete tse tloaelehileng UL1-DE019586, UL1-RR024139 (Yale CTSA), le PL1-DA024859.
Mongolo o botlaaseng ba leqephe
Boitlhotlhollo ba Mohoeletsi: Ena ke faele ea PDF ea mongolo o ngotsoeng ka letsoho o sa amoheloang o amoheletsoeng bakeng sa ho hatisoa. Joaloka tšebeletso ho bareki ba rona re fana ka phetolelo ena ea pele ea mongolo o ngotsoeng ka letsoho. Mongolo o ngotsoeng ka letsoho o tla ba le ho kopitsa, ho kenya lihlopha le ho hlahloba bopaki bo hlahang pele o hatisoa ka mokhoa oa oona oa ho qetela. Ka kopo hlokomela hore nakong ea mekhoa ea tlhahiso ea lihlahisoa e ka fumanoa e ka amang litaba, le litsebiso tsohle tsa molao tse sebetsang koranteng e amanang le eona.
Litlhaloso tsa lichelete: Dr. Sinha o setsi sa Scientific Advisory Board bakeng sa Embera Neutotherapeutics. Ania Jastreboff o thusa ManPower ea fanang ka bo-rakhoebo bakeng sa Pfizer New Haven Clinic Research Unit.
References