Bophelo bo botle ba ho ja lijo tse ngata tse nonneng bo khothalletsa liphetoho tsa nako e telele litabeng tsa lijo le phalliso e kholo (Deltafosb e fokotsa dopamine pontšo) (2009)

Neuroscience. Sengoloa se ngotsoeng; e fumaneha ho PMC Sep 15, 2010.
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inahaneloang

Ho nona le ho nona haholo United States ho ntse ho hola ka bongata ka lebaka la tšebeliso e matla ea lijo tse matlafatsang tse nang le letsoai. Ho tsebahatsa lintlha tse susumetsang likhetho tsa nako e telele tsa macronutrient ho ka hlakisa lintlha tsa thibelo le boits'oaro. Thutong ea rona ea hona joale, re ile ra hlahloba likhetho tsa macronutrient tsa baholo ba litoeba tse pepesitsoeng lijong tse phahameng tsa mafura bekeng ea boraro ea kamora ho pepa. Re ile ra nahana hore tšebeliso ea lijo tse nang le mafura a mangata nakong ea bophelo ba pele e ne e tla fetola mananeo a litsela tsa mantlha litabeng tsa lijo tsa batho ba baholo. Ha e le batho ba baholo, litoeba tsa pele tse senotsoeng li bonts'itse khetho ea bohlokoa ea phepelo e phahameng ea mafura ha e bapisoa le taolo. Phello ena e ne e se ka lebaka la tloaelo ea lijo hobane litoeba tse senotsoeng ke phepo e phahameng ea "carbohydrate" nakong eona ena ea pele li ile tsa sitoa ho bonts'a phapang litakatsong tsa macronutrient joalo ka batho ba baholo. Tekanyo e ntseng e eketseha ea ho ja lijo tse phahameng mafung a litoeba tsa pele tse senotsoeng e ne e ikhethile molemong oa lijo ka ha ho se liphetoho tse fumanoeng bakeng sa tšebeliso ea caloric e felletseng kapa ka katleho. Mekheniki, litoeba tse pepesetsoeng lijo tse nang le mafura a mangata nakong ea bophelo ba pele li ile tsa bonts'a liphetoho tse kholo matšoao a biochemical a dopamine a saenneng bokong ba li-nucleus, ho kenyelletsa le liphetoho maemong a phospho-DARPP-32 Thr-75, ΔFosB, le Cdk5. Liphetho tsena li ts'ehetsa monahano oa rona oa hore le bophelo bo bokhutšoaane ba bophelo bo sa ts'oaneng le lijo tse matlafatsang tse nang le phepo ea nako e telele li bohlokoa li fetoleng mananeo a mahareng a bohlokoa methating ea lijo le moputso. Liphetoho tsena li ka baka khatello e matla ea lijo tse mafura a mangata tse tlatsetsang ho eketseheng ha boima ba 'mele lefats'eng la Bophirimela.

Keywords: dopamine, striatum, macronutrient, nts'etsopele

Lefu la seoa la ho nona haholo United States le ntse le eketseha, lipalo-palo tsa morao-rao li bonts'a hore batho ba baholo ba Amerika ba fetang 60% ha joale ba nonne haholo kapa ba batenya haholo (Ogden et al. 2006). Tloaelo e 'ngoe, e bohlokoa ka ho lekana ke sekhahla se ntseng se eketseha sa botena ba bongoana (Ogden et al. 2002). Bana ba mekheng ea Bophirimela, ntle le bophelo bo ntseng bo eketseha ba ho lula, ba pepesetsoa lijo tse fapaneng tse nang le mafura le lik'hilojule tse ngata tse tlatsetsang ho holiseng botenya. Bana ba batenya ho feta tekano ba ka ba batho ba baholo ba batenya, mohlomong ka karolo e 'ngoe ka lebaka la ho phehella ha mekhoa le mananeo a ho rata lijo a ntlafalitsoeng nakong ea bongoana (Serdula et al. 1993).

Boithuto bo bontšitse hore ho pepesehela litakatso tse itseng tsa tatso nakong ea bongoana le bongoaneng ho ka fetola litakatso tsa lijo ho bana lilemo tse tlang hamorao (Johnson et al. 1991; Kern et al. 1993; Liem le Mennella 2002; Mennella le Beauchamp 2002). Leha ho le joalo, mekhoa eo litlamorao tsa nako e telele joalo e bileng teng ha e so hlakisoe. Ka hona, re ile ra hlahloba litlamorao tsa ho pepesetsoa lijo tsa pele ho lijo tse nang le mafura a mangata ho litakatso tsa batho ba baholo ba macronutrient ka litoeba. Litsuonyana li ile tsa pepesetsoa phepelo e phahameng ea mafura bakeng sa beke e le 'ngoe, ho tloha matsatsing a pelehi 21-28 (P21-28), nako eo li qalang ho ja lijo tse tiileng ebile ha li sa itšetleha ka letamo bakeng sa phepo. Ha o khoesoa, litoeba li ne li khutlisetsoa 'mala o tloaelehileng oa ntlo ebe li hlahlojoa hore na li khetha' mino o mong oa macronutrient le ho ja lijo tse nang le mafura a mangata joaloka batho ba baholo. E ipapisitse le lithuto tse fetileng tse bonts'a phello ea lijo tse matlafatsoang liteisheneng tsa meputso ea boko le liphetoho dopamine sign (Teegarden le Bale 2007; Teegarden et al. 2008), re boetse re hlahlobe matšoao a biochemical maemong a litoeba tsena. Re ile ra nahana hore ho pepesetsoa lijo tse nang le mafura a mangata nakong ea bophelo ba mantlha ho ka etsa hore batho ba natefeloe ke lijo tse matla haholo ha ba se ba le baholo ka liphetoho lipakeng tsa meputso e khothalletsang tšebeliso ea lijo tse matla le tse matlafatsang.

Mekhoa ea Boiteko

Liphoofolo le Phatlalatso ea Lijo tsa Pele

Lice li hlahisitsoe C57Bl / 6: 129 ea morao-rao e le karolo ea kolone ea ka tlung. Linokoane tsena li bile sehlopheng sa batho ba tsoakaneng lilemo tse fetang tse leshome (Bale et al. 2000), ka ho kenyelletsa letamo le lecha la gene lilemo tse ling le tse ling tse peli ka ho tsoala ka F1 C57Bl / 6: sefapano sa 129. Ho li-wks tsa 3 tsa lilemo, litter li ile tsa pepesetsoa lijo tse nang le mafura a mangata (Lipatlisiso tsa Diets, New Brunswick, NJ) bakeng sa beke e le 'ngoe. Lijo tse nang le mafura a mangata li ne li na le 4.73 kcal / g mme li na le mafura a 44.9%, 35.1% carbohydrate, le 20% protheine. Literata tse laoloang li ile tsa sala li le holim'a matlo a tloaelehileng (Purina Lab Diet, St. Louis, MO). House chow e ne e na le 4.00 kcal / g mme e ne e na le mafura a 12%, carbohydrate ea 60%, le proteni ea 28%. Nako ena ea ho pepesetsoa lijo li ne li khethoa joalo ka 3 wks ea lilemo, bana ba ja lijo tse tiileng mme ha ba its'epahalle ke mme bakeng sa phepo. Kamora ho khoesoa, litoeba tsohle (n = 16 taolo, 14 ea pele e mafura a phahameng e pepesitsoe) e ile ea bolokoa holima ntlo ho fihlela likhoeli tsa 3. Lithuto tsohle li entsoe ho latela liprotheine tse lumelletsoeng ke Komiti ea Tlhokomelo ea liphoofolo le Tikoloho ea Univesithi ea Pennsylvania, mme lits'ebetso tsohle li entsoe ho latela tataiso ea setheo.

Khetho ea Likhetho tsa Macronutrient

E le ho hlahloba hore na ho pepesetsoa lijo tsa macronutrient tse ntlafalitsoeng pele ho nako ho ka ama likhetho tsa lijo tsa batho ba baholo joang, litoeba tsa khoeli le khoeli tsa 3 li ile tsa hlahlojoa bakeng sa khetho ea khetho ea macronutrient ho feta matsatsi a 10. Liceu li ile tsa lumelloa ho lula ntlong e le 'ngoe ea 1 wk pele ho khethoa. Li-pellets tse boima ba 'mele tse nang le mafura a mangata, lik'habohaedreite tse ngata le lijo tse nang le protheine e ngata li ile tsa beoa mokatong oa likhomo. Lijana tsa litoeba le lijo li ne li imeloa letsatsi le letsatsi. Lijo tse phahameng tsa lik'habohaedreite tse nang le 3.85 kcal / g e nang le mafura a 10%, 70% carbohydrate le protheine ea 20%. Lijo tse phahameng tsa protheine li ne li na le 4.29 kcal / g mme li na le mafura a 29.5%, 30.5% carbohydrate, le protheine ea 40%. Lijo tse nang le mafura a mangata tse sebelisitsoeng li ne li ts'oana le se neng se sebelisoa ho pepesetsoa batho ba pele.

Bakeng sa ho laola litlamorao tsa tloaelo ea ho ja ka lithahasello tsa macronutrient, re boetse ra hlahloba lithaelese tse arohaneng tse senotsoeng ke phepo e phahameng ea nama ea nama ea nama ea kolobe (Dijo tsa Patlisiso, joalo ka ha ho hlalositsoe kaholimo), ho tsoa ho 3-4 wks ea lilemo le ho hlahlojoa bakeng sa khetho ea macronutrient joaloka batho ba baholo (n = 6).

Batho ba baholo ba na le phepo e ngata e phahameng ea ho ja

Kamora ho khethoa ha khetho ea macronutrient, sete sa litoeba (n = 7 taolo, ho pepesetsoa mafura a phahameng a 9) li ile tsa pepesetsoa lijo tse nang le mafura a mangata bakeng sa li-wks tsa 15 e le hore ho hlahlojoe tšebeliso le litlamorao tsa phepo e phahameng ea mafura le nts'etsopele ea monyetla oa botenya ho litoeba tse neng li pepesehetse lijo tsena nakong ea bophelo ba hae ba pele. Lijana li ne li lekantsoe beke le beke nakong ena, 'me lijo tsa 24-hr li ne li lekanngoa nakong ea beke e le' ngoe kamora ho pepeseha ha 6 nako e telele. Qetellong ea nako ea phepo e phahameng ea mafura a mangata, litoeba li ne li etsoa sethethefatsi ka ho latela nakoana ka mora isoflurane anesthesia, 'me ho bokelletsoe lithane tsa adipose, plasma le sebete.

Bofetoheli le plasma leptin

Ha ho etsoa mahetla, litoeba li ne li lekantsoe 'me lisele tsa "adipose" tse sootho le li-depo tse tšoeu tsa reipose tse tšoeu li ile tsa tlosoa hape tsa beoa. Mali a kutu a ile a bokelloa ka meqomong e nang le 50 mM EDTA le centrifuged bakeng sa 10 min ho 5000 rpm le 4 ° C ho arohana le plasma. Plasma e ne e bolokiloe ka -80 ° C ho fihlela e ts'oaroa. Maemo a Leptin a ne a khethiloe ke radioimmune assay (Pato ea Lipatlisiso, St. Charles, MO). Ho sebelisitsoe sampole e mashome a mahlano ea plasma ka mohlala, 'me mehlala eohle e ne e etsoa ka likopi tse peli. Boikutlo ba tlhaselo eo e ne e le 0.2 ng / ml, mme li-corafficients tsa intra- le interassay tsa phapang e ne e le 7.2% le 7.9% ka ho latellana.

Tlhahlobo ea biochemical

Ha ho etsoa sehlabelo, boko bo ile ba tlosoa ka potlako, ventral striatum (e ka bang 0.5 - 1.75 mm ho tloha bregma, botebo ba 3.5 - 5.5 mm) ea aroloa (Teegarden le Bale 2007), 'me lithane li hoamme hanghang ho naetrojene ea metsi. Li-blots tsa Bophirimela (n = 4 taolo, n = 5 ponahallo e phahameng ea mafura) e entsoe joalo ka ha ho hlalositsoe pele ho sebelisoa phosphatase inhibitor cocktail (P2850 Sigma, St. Louis, MO) ho boloka boemo ba phosphorylation (Bale et al. 2003; Teegarden le Bale 2007). Li-antibodies tse sebelisitsoeng e ne e le FosB (1: 200; Santa Cruz Biotechnology, Santa Cruz, CA), Cdk5 (1: 500; Santa Cruz Biotechnology), phospho-DARPP-32 Thr 75 (1: 200; Theknoloji ea ho saena sele, Danvers, MA) , phospho-DARPP-32 Thr 34 (1: 500; PhosphoSolutions, Aurora, CO), DARPP-32 e felletseng (1: 500; R&D Systems, Minneapolis, MN), le receptor opioid (1: 500; Abcam, Cambridge, MA). OsBFosB e ne e khethollotsoe ho FosB e bolelele bo felletseng ka boima ba 'mele (Nestler et al. 2001). Lirosa tsohle li ile tsa nkuoa mme tsa khethoa hape bakeng sa β-actin bakeng sa tloaelehileng (1: 1000; Sigma, St. Louis, MO). Blots e ile ea hlahlojoa ho sebelisoa software ea IPLab (Teegarden le Bale 2007). Litholoana tsa methapo ea kutlo bakeng sa liprotheine tsa sepheo li ile tsa aroloa ka boleng ba β-actin kahare ho sampole ka 'ngoe ho lokisa bakeng sa ho jarolla phoso.

Lipalo-palo li

Lintlha tsohle li ile tsa hlahlojoa ho sebelisoa t-teko ea moithuti ka kalafo ea pele ea lijo e le phapano e ikemetseng. Lintlha tsohle li hlahisoa e le moelelo ± SEM.

Results

Khetho ea Likhetho tsa Macronutrient

Ho fumana hore na ho pepesetsoa lijo tsa pele ho ama likhetho tsa batho ba baholo tsa lijo joang, litoeba tse pepesetsoeng phepelo e phahameng ea mafura ho tsoa li3-4 wks ea lilemo li ile tsa hlahlojoa bakeng sa khetho ea khetho ea macronutrient bakeng sa matsatsi a 10 ho qala ka likhoeli tsa 3. Khetho ea lijo tse nang le mafura a mangata (tse tlalehiloeng e le liperesente tsa likhalori tse felletseng e le lijo tse phahameng tsa mafura; Setšoantšo sa 1A) e ne e le kholo ho litoeba tse neng li pepesitsoe ke phepo e mafura nakong ea bophelo ba pele (P <0.05). Ho khetha lijo tse phahameng tsa protheine ha hoa ka ha fetoloa haholo ke ho pepeseha ha lijo tsa pele ho nako (P = 0.17). Litoeba tse neng li pepesitsoe lijo tse mafura haholo li ne li ja lijo tse fokolang haholo ho feta taolo (P <0.05). Karolelano ea phepelo ea likhalori tsa letsatsi le letsatsi lipakeng tsa taolo le litoeba tsa pele tse mafura a mangata li ne li sa fapana (Setšoantšo sa 1B). Ha ho ja lijo tsa letsatsi le letsatsi ho hlalosoa e le ligrama tsa lijo tse jeoang, ho ne ho boetse ho se na phapang ea bohlokoa lipakeng tsa lihlopha (taolo = 3.29 ± 0.13 g / letsatsi, mafura a phahameng a pele a senotsoe = 3.15 ± 0.14 g / day).

Setšoantšo sa 1 

Ho pepesetsoa bophelo bo bonyane ha motho a sa le monyane ho ja lijo tse nang le mafura a mangata ho fella ka ho eketseha ha mafura nakong ea ho ba motho e moholo. (A) Litoeba li fumane lijo tse nang le mafura a mangata kapele pele li khoesoa (HF ea pele) li qetile karolo ea likhalori tsa tsona ka bongata ...

Boima bo boholo ba 'mele bo ne bo sa fapana haholo pakeng tsa lihlopha tsa kalafo pele kapa kamora khetho ea macronutrient (Setšoantšo sa 1C). Bokhabane ba caloric bo ile ba baloa ha boima bo ntse bo fumanoa (g) / khalori e sebelisitsoeng (kcal) nakong ea teko. Ho ne ho se na phapang ea katleho ea caloric pakeng tsa lihlopha ha u ntse u khetha likhetho tsa macronutrient (Setšoantšo sa 1D). Sena se fana ka maikutlo a hore le ha ho pepesetsoa lijo tsa mafura a mangata ho eketsa ho rata ha batho ba baholo bakeng sa lijo tse phahameng tsa mafura, ha ho lebise phetohong ea ho ja kapa ho atleha ha caloric ka botlalo.

Bakeng sa ho laola litlamorao tsa tloaelo ea ho ja ka ho rata lijo tsa nako e telele, sehlopha sa litoeba se arohaneng se fumane phepo e phahameng ea carbohydrate ho tsoa ho 3-4 wks ea lilemo. Litoeba tsena ha lia ka tsa bontša liphetoho likhethong tsa macronutrient bakeng sa lik'habohaedreite tse ngata kapa mafura a mangata a amanang le taolo (Setšoantšo sa 1E), e ts'ehetsa phello e matla e amanang le phepo e phahameng ea mafura lits'ebetsong tsa boko tse laolang likhetho tsa lijo.

Lijo tse phahameng tsa Fat

Litsuonyana li ile tsa pepesetsoa lijo tse matla tse sa feleng tsa mafura le ho ja lijo, boima ba 'mele, maemo a phahameng le maemo a plasma leptin. Ho ne ho se na phapang e kholo karolelanong ea lijo tsa letsatsi le letsatsi, boima ba 'mele ba ho qetela, kapa katleho ea khalori nakong ea phello e phahameng ea lijo.Feiga. 2A-C). Ha ho na liphapang ka tekanyo e lekanang ea mafura a 'mele lipakeng tsa lihlopha kamora likhoeli tsa 3 lijong tse phahameng tsa mafura (Setšoantšo sa 2D). Ho feta moo, ho ne ho se na phapang lipakeng tsa lihlopha tse maemong a plasma leptin kamora ho ja haholo mafura a mangata (Setšoantšo sa 2E).

Setšoantšo sa 2 

Ha ho na phapang e ileng ea bonoa lipakeng tsa lihlopha bakeng sa lijo le boima ba 'mele nakong ea khoeli ea 3 ea khoeli le khoeli ea ho pepeseha mafura a mangata. (A) Takatso ea khalori ea letsatsi le letsatsi e ne e sa tšoane lipakeng tsa taolo (Ctrl) le litoeba tse phahameng tsa mafura a pele (a HF) ea mantlha ha litoeba li le ...

Biochemistry ho Ventral Striatum

Kamora ho pepesetsoa phepo e sa foleng ea mafura a mangata, matšoao a biochemical a ho bontša moputso a ile a hlahlojoa ho litoeba tsena. Litoeba tse pepesitsoeng phepelo e phahameng ea mafura nakong ea bophelo ba pele li bontšitse maemo a phahameng haholo a sengoloa sa sengoloa ΔFosB (P <0.05; Setšoantšo sa 3A). ΔFosB e bontšitsoe hore e susumetsa polelo ea cyclin-based kinase 5 (Cdk5) (Bibb et al. 2001). Tumellanong le mofuta ona, litoeba tsa pele tse nang le mafura a mangata li pepesitse litoeba hape li bonts'a maemo a phahameng a Cdk5 ho striatum (P <0.05; Setšoantšo sa 3B). Cdk5 phosphorylates protheine dopamine le phamphone e laoletsoeng ea cAMP, boima ba molek'hule 32 kDa (DARPP-32) ho threonine 75 (Bibb et al. 1999). Litoeba tse pepesitsoeng phepo e mafura haholo nakong ea bophelo ba bongoana le tsona li bontšitse maemo a phahameng haholo a phospho-DARPP 32 Thr 75 (P <0.05; Setšoantšo sa 3C). Litoeba tsena li boetse li bonts'a mokhoa o seng oa bohlokoa bakeng sa phokotso e tšoanang ea phosphorylation ea DARPP-32 ho Thr 34 (P <0.10; Setšoantšo sa 3D). Maemo a liprotheine tse felletseng tsa DARPP-32 ho striatum ha aa ka a fetoloa ke kalafo ea phepo ea pele (P = 0.78; Setšoantšo sa 3E). Ts'ebetso ea ts'ebetso ea opioid ho striatum e boetse e amana le tšebeliso e matla ea lijo tse matlafatsang. Ka ho khetheha, receptor ea mu opioid e hokahane haholo le ts'ebeliso e eketsehileng ea lijo tse ratoang. Ka hona, re fuputse maemo a receptor ea 'mu sebakeng sena (Zhang et al. 1998). Maemo a ne a sa fapana pakeng tsa taolo le litoeba tsa pele tsa mafura a senotsoeng (P = 0.90; Setšoantšo sa 3F).

Setšoantšo sa 3 

Matšoao a dopamine a tšoaeang ka har'a ventral striatum a ile a fetoloa ka litoeba tse pepesitsoeng ho ja lijo tse phahameng tsa mafura bophelong ba pele (HF ea pele). (A) Bophahamo ba ntlha ea sengoloang ΔFosB e ne e phahamisitsoe haholo litulong tsa litoeba tsa batho ba baholo ...

Puisano

Boithuto ba likhetho tsa lijo ho masea le ho bana bo bontšitse hore ho pepesehela litatso tse fapaneng ho ka lebisa ho amoheloeng le litakatso tsa litatso tsena bophelong ba kamoso.Liem le Mennella 2002; Mennella le Beauchamp 2002). Ha bana ba ntse ba pepesetsoa lijo tse nang le mafura a mangata haholo bongoaneng, ho bohlokoa ho tseba hore na ho pepesetsoa lijong tse itseng ka nako ena ho ka ama lijo tseo o li ratang nakong ea ho ba motho ea moholo, hape ho ba le seabo se ka etsang hore ho be le lijo tse matlafatsang tse matlafatsang. Thutong ea hajoale, re ithutile hore na ho pepesehela lijo tse nang le mafura a mangata joang nakong ea periweaning (3-4 wks ea lilemo), ha litoeba li ja lijo tse matla ebile li sa itšetleha haholo ka letamo bakeng sa phepo, li ka ama likhetho tsa batho ba baholo ba macronutrient, lijo, le phaello ea boima ba 'mele.

Tlhahlobong ea letsatsi le letsatsi ea ho khetha li-macronutrient tsa 10 tsa letsatsi, lijo tse phahameng tsa mafura li bonts'itse khetho e kholo haholo ea lijo tse phahameng tsa mafura joalo ka batho ba baholo, tse lekantsoeng ka tekanyo ea karolelano ea caloric ea letsatsi le letsatsi. E le taolo ea tloaelo ea ho ja, litoeba tse senotsoeng phepelong e phahameng ea lik'habohaedreite nakong ea bophelo ba pele li sa bonts'a phapang litakatsong tsa batho ba baholo ba macronutrient, li fana ka tlhahiso ea hore liphetoho tse ratoang ke batho ba baholo ha se lebaka la boiphihlelo ba pele le lijo. Liphetoho lijong tsa bo-mme li amahantsoe le litakatso tse fetotsoeng bakeng sa li-macronutrients, ka liprotheine tse tlase le lijo tse nang le mafura a mangata li eketsa ho rata lijo tse mafura a mangata lilemong tsa pele, le ha phapang ena e fokotseha le lilemo (Bellinger et al. 2004; Kozak et al. 2005). Le ha ho le joalo, mekhoabo ana a etsahala nakong ea boitšisinyo ba mmele le morusu ha boko bo ntse bo ntlafala ka hona ha ho na monyetla oa ho ikarabella bakeng sa litlamorao tse bonoang mona. Ho khahlisang, ho pepesetsoa ha mofuta o monate oa tsoekere (Froot Loops cereal) e tsoang P22-27 e bontšitsoe ho eketsa tšebeliso ea ntho ena ho ba motho e moholo.Silveira et al. 2008). Leha ho le joalo, liqeto tse tsoang mosebetsing ona li boetse li fana ka maikutlo a hore liphetoho tsa ts'ebeliso li bakoa haholo ke phihlello e fokolang e fanoeng le tikoloho e ncha eo lijo li hlahisitsoeng ho eona ho feta phetoho efe kapa efe eo likhoto li e ratang. Ka ho sebelisa phepo e felletseng e nang le limatlafatsi tse ngata e hlahisitse ad libitum tikolohong ea li-cage tsa lapeng, re atlehile ho lekola liphetoho likhethong tsa lefatše tsa lijo. Hobane nako ea tlhahiso ea lijo e etsahetse morao haholo nts'etsopele, ha ho na monyetla oa hore liphetoho ho li-wiring tsa neural ho fepa le ho putsa lipotoloho li ikarabella bakeng sa liphetoho tse bonoang boitshwarong, le hore mekhoa e meng, joalo ka liphetoho tsa epigenetic, e kanna ea ba teng.

Leha ho na le keketseho e lekanang ea ho ja lijo tse phahameng tsa mafura a hlokometsoeng litoeba tse sa bonoang, ho ne ho se na phapang lipakeng tsa karolelano ea caloric ea letsatsi le letsatsi kapa ho nona ka boima nakong ea khetho ea likhetho tsa macronutrient. Limpho li ja lijo tse nang le mafura a mangata haholo ka ho fokotsa lik'hilojule tse ngata haholo ka ho fokotsa lijo tse matlafatsang tse nang le macronutrient, haholo-holo lijo tse phahameng tsa lik'habohaedreite. Ka kakaretso, liphetho tsena li fana ka maikutlo a hore ts'usumetso ea ho pepesetsoa batho ba pele e ho khethoa feela, mme eseng ho ja lijo kapa metabolism ka kakaretso. Ho kanna ha eba bolelele ba teko ea khetho ea macronutrient bo boholo bo eketsehile, phapang ea boima ba 'mele le katleho ea caloric e ka be e ile ea hlaha ka lebaka la keketseho e telele ea ho ja mafura. Leha ho le joalo, nakong ea phello e matla ea lijo tse mafura tse ngata, ha rea ​​ka ra bona ho se tšoane lipakeng tsa lihlopha tsa batho ba jang, ho nona, kapa ho rata maemo, ho ts'ehetsa ka ho hlaka phello ea ho pepeseha hoa bophelo ba mantlha ho latela khetho ea lijo.

Mekheniki, re fuputse lisosa tse ka bang teng molemong oa ho rata lijo tse mafura haholo. Nako eo tlhahiso ea lijo e hlahang thutong ea hona joale e entse hore ho se be le monyetla oa hore litlamorao tse tobileng ho hypothalamus li ikarabelle bakeng sa phenotype. Ho potoloha ha motsoako oa arcuate, setsi sa mantlha se laolang lijo, se thehiloe haholo bekeng ea bobeli ea bophelo, ka likhokelo tse tšoanang le tsa phoofolo e moholo ke P18 (Bouret et al. 2004). Tlhaloso ea li-peptide tse ka sehloohong tsa orexigenic le anorexigenic, neuropeptide Y (NPY) le pro-opiomelanocortin (POMC), le tsona li fetoha nakong ea kholo ea pelehi kamora ho pepa, ho fihla maemong a batho ba baholo ho potoloha beke ea boraro ea bophelo (Ahima le Hileman 2000; Grove et al. 2003; Leibowitz et al. 2005). Li-neuron tse arcuate li fetoha leptin le ghrelin lipakeng tsa libeke tse peli le tse nne kamora ho hlaha (Mistry et al. 1999; Proulx et al. 2002). Boholo ba lithuto tse mabapi le litlamorao tsa phepo e nepahetseng mantlha li kenyelletsa manong a lijo nakong ea ho emara le / kapa ho nyekeloa, e le hore li ka holisa nako ena ea polasetiki ho "rodent hypothalamus". Ka beke ea bone ea bophelo, ha tlhahiso ea rona ea mafura a mangata e qalile, nts'etsopele ea hypothalamic e phethehile haholo. Leha ho le joalo, ho na le bopaki bo itseng ba polasetiki e fokolang ho hypothalamus ea batho ba baholo (Horvath 2005; Kokoeva et al. 2005). Re ke ke ra tseba hore na ho ka ba le tlatsetso e fe ea liphetoho tse joalo mofuteng oa rona oa qetello.

Likhetho tsa lijo tse matlafatsoang li hokahane haholo le lits'ebetso tsa moputso, ka lijo tse ratoang haholo li na le litlamorao tse kholo ho lokollotsoeng ha dopamine (DA) ho li-nucleus accumbens, le liphetoho mesebetsing ea DA e lebisang phetohong ea boitšoaro ba ho fepa (Blum et al. 2000; Colantuoni et al. 2001; Colantuoni et al. 2002; Cagniard et al. 2006). Ntle le moo, mananeo a phepo ea phepo ea pele kapa ho pepesetsoa tlhoko e putsang ea litoeba a bontšitsoe ho ama tšebetso ea nako e telele ea sistimi ea DA (Sato et al. 1991; Zippel et al. 2003; Kelley le Rowan 2004). Re kile ra tlaleha hore ho tlohela lijo tse nang le mafura a mangata ho ka ba le litlamorao tse telele le tsa nako e telele tsamaisong ea DA (Teegarden le Bale 2007; Teegarden et al. 2008). Kahoo, thutong ea hona joale re fane ka maikutlo a hore pontšo ea moputso e ka fetoloa litoeba tse pepesetsoeng lijong tse phahameng tsa mafura nakong ea bophelo ba hae ba pele. Ho etsa tlhahlobo ea maikutlo ana, litoeba li ile tsa etsoa sehlabelo ka mor'a ho pepesetsoa mafura a mangata le ho tšoaea matšoao a bontšang moputso ho li-ventral striatum. Re fumane hore litoeba li pepesetsoa phepelo e phahameng ea mafura nakong ea bophelo ba pele li ne li na le lintlha tse phahameng haholo tsa phetisetso ea criptionFosB maemong a morao a latelang ho pepesetsoa mafura a mangata ka lebaka la ho ba motho e moholo. ΔFosB e kenyellelitsoe molemong oa ho pepesehela lithethefatsi tsa tlhekefetso le meputso ea tlhaho (Nestler et al. 2001; Teegarden le Bale 2007; Wallace et al. 2008). ΔFosB e nang le bothata bo boholo ba "dynorphin" e nang le "spinyal" e nang le "dynorphin" e khothatsang haholo e fana ka sepheo se eketsehileng sa ho fumana moputso oa lijo ka lebaka la ho se sebetse hantle ha lets'oaetso la DA.Olausson et al. 2006; Teegarden et al. 2008). Mosebetsi oa rona o bonts'itse hore litoeba tsena li kotsing e kholo ea ho tlosoa ke phepo e phahameng ea mafura hape li bonts'a liphetoho tse kholo ho matšoao a DA a latelang ho pepesetsoa mafura a mangata (Teegarden et al. 2008). Re boetse re hlokometse keketseho e kholo ea "cyclin-based kinase 5" (Cdk5) le dopamine le cAMP e laoloang ke phosphoprotein, boima ba molek'hule 32 kDa (DARPP-32) phosphorylated ho threonine 75, hammoho le mokhoa oa phokotso e tsamaellanang ea 32 Thr 34. Ts'ebetsong ea ho supa boiphihlelo bo latelang ba moputso le ho nyoloha ha ΔFosB, maemo a Cdk5 a qala ho nyoloha (Bibb et al. 2001). Joalo ka taolo e mpe ea li-neurotransication tsa DA le thabo ea neuronal (Chergui et al. 2004; Benavides et al. 2007), Phdk5 phosphorylates DARPP-32 ho threonine 75 (Bibb et al. 1999). Ho khahlisang, phosphorylation ea DARPP-32 setsing sena e bonts'a tšebetso ea D1 DA receptor ka thibelo e tobileng ea protheine kinase A le inhibits phosphorylation ho Thr 34 (Benavides le Bibb 2004). Ka kakaretso, mehato ena ea biochemical e khothaletsa phello ea phokotso ea phetisetso ea matšoao a DA ka striatum nakong ea ho pepesetsoa lijo tse phahameng mafung a litoeba tse neng li kile tsa pepesetsoa ho tsoa lijong tsa mafura a mangata nakong ea bophelo ba hae. Re nahana ka hore ho fokotseha ha letšoao la DA ho bonoang nakong ea ho pepesetsoa lijo tse mafura a mangata ho kanna ha tlatsetsa ho khethoeng ha mafura a mangata nakong ea khetho e kholo ea macronutrient. Nakong ea ho pepesehela mafura a mangata a mafura a mangata, ho ka etsahala hore tšebeliso e lekanyelitsoeng ke tšebeliso ea caloric e felletseng, ka hona ha ho liphapang tsa boitšoaro tse ileng tsa bonoa. Lintlha tsa rona li tsamaellana le litlaleho tsa bongaka tse fanang ka tlhahiso ea ho fokotsa matšoao a DA ho bakuli ba batenya haholo (Wang et al. 2001). Keketseho ea khetho ea lijo tse phahameng tsa mafura botsofaling e kanna ea ba karabelo e tlatselletsang ke setho e le ho fetolela modumo oa dopaminergic (Blum et al. 2000; Wang et al. 2004; Teegarden et al. 2008).

Mochini o fetotseng liphetoho tsena ho saena dopamine o sa ntse o lokela ho hlakisoa. Ho bohlokoa ho hlokomela hore liphetoho tse hlahisitsoeng ke opioid signaling in the ventral striatum li boetse li hokahane haholo le liphetoho phepong e bonolo le ho lets'oao la dopaminergic. Haholo-holo, ho hlohlelletsoa ha 'mele oa opioid receptor ho lebisa keketseho e matla ea ho ja lijo tse nang le mafura a mangata (Zhang et al. 1998), le ho pepesetsoa lijo tse nang le mafura a mangata ho ka fetola sesupo sa opioid (Blendy et al. 2005; Jain et al. 2004). Leha ho le joalo, ha rea ​​ka ra bona ho se tšoane ka maemo a 'mele oa "opioid receptor" pakeng tsa taolo le lijo tsa mafura a mantlha tse senotsoeng. Le ha hona ho sa fane ka karolo ea lipalo tsa li-receptor signature kapa lintlha tse ling tsa opiodergic, datha ea rona e bonts'a hore phetoho ea khetho ea lijo e bakoa ke liphetoho dignamine signature tse sa amaneng le liphetoho maemong a li-receptor tsa mu opioid.

Ka rat, li-neuron tsa dopamine li tsoaloa ho pota letsatsi la embryonic 12 (E12) mme li qala ho atolosa lits'ebetso ho E13. Ho sibolloa ha striatum ho fetela bekeng ea pelehi ea kamora ho ts'oaroa, 'me tlhophiso e ntse e tsoela pele bonyane ho fihlela bekeng ea boraro ea pelehiVan den Heuvel le Pasterkamp 2008). Ka hona, paradigm ea phepelo ea lijo thutong ea hona joale ha e na monyetla oa ho fetola sebopeho sa mantlha sa mesolimbic dopamine system. Liphetoho maemong a mafura a acid nakong ea nts'etsopele le bophelo ba kamora nako li ka ama maemo a DA le DA receptor karolong e ka pele ea likhoto tse kholo (Delion et al. 1994; Delion et al. 1996; Zimmer et al. 1998), le tšebeliso ea 'mele ea lijo tse nang le phepo e phahameng ea bo-mme li ka fetola tšebetso ea sistimi ea DA ho bana ba baholo, mohlomong e lebisang ho nyahameng ha dopamine receptors (Naef et al. 2008). Leha lijo tse sebelisitsoeng thutong ea rona ea hona joale li ne li na le mafura a mangata, menyetla e ntse e le teng ea hore phapang e poteletseng ea mafura a ja e ka fetola liphetoho tsa nako e telele tsa DA. Ntle le moo, litlamorao tsa nts'etsopele tse tobileng tse ka bonoang mefuteng ea phetisetso ea lijo tsa bo-mme li ka se be le boikarabello bakeng sa liphetho tsa hona joale ka lebaka la nako ea morao ea tlhahiso ea lijo, ho fana ka maikutlo a hore mekhoa ea epigenetic e ka bapala karolo. Plasticity ho li-nucleus accumbens e boetse e bonoa ka mor'a kalafo e nang le lithethefatsi tsa tlhekefetso. Cocaine, nikotini le amphetamine li eketsa letsoalo la lesapo sebakeng sena (Robinson le Kolb 2004). Liphetoho tsena li nka likhoeli tse ngata kamora ho pepesetsoa lithethefatsi, mme li ka susumetsoa ke boiphihlelo bo le bong feela.Kolb et al. 2003). Re kile ra bonts'a hore ho ikhula lijong tse phahameng tsa mafura ho batho ba baholo ho hlahisa phetoho maemong a sithabetsang le meputso tseleng ea litoeba (Teegarden le Bale 2007). Ka hona, ho a khonahala hore ho pepesetsoa le ho khutla hoa lijo tsena nakong ea bophelo ba pele ho bophelo ho hlahisa litlamorao tse ts'oanang tse ntlafatsang li-circuits tsena. Kamora nako, mokhethoa e mong oa ho tsamaisa phetoho ea nako e telele ho polelo ea gene ke molaoana oa epigenetic. Ho qhekella ho ja lijo le hona ho ka lebisa ho lenaneo la nako e telele la polelo ea liphatsa tsa lefutso ka liphetoho ho methapo ea methapo ea methapo kapa histone acetylation. Liphetoho ho methylation ea liphatsa tsa lefutso tsamaisong ea DA li hokahane le mathata a kelello le khatello ea maikutlo hammoho le bokhoba ba tahi (Abdolmaleky et al. 2008; Hillemacher et al. 2008). Le ha lithuto tsena li sa sebetsane ka kotloloho le litlamorao tsa phepelo e phahameng ea mafura holim'a polasetiki ea DA system, li phahamisa monyetla o makatsang oa hore ts'ebetso ea sistimi ena e ka fetoloa nako e telele ke moputso oa tlhaho nakong ea bophelo ba pele. Mechine ena e ka hlahlojoa ka ho eketsehileng lithutong tse tlang.

Qetellong, thuto e teng hona joale e bonts'a hore ho pepesetsoa lijo tse matlafatsang tse mafura haholo nakong ea bophelo ba pele ho sa natefeloa ke ho tloaela lijo. Ka tekano, ho fetisoa ha lets'oao la DA maemong a litoeba tsena ho ka etsa hore ho be le khetho e matla bakeng sa phepelo e phahameng ea mafura boitekong ba ho etsa maemo a DA maemong. Boitsebiso bo fana ka tlhahiso ea hore ho pepesetsoa lijo tse matlafatsang tse nang le phepo e ngata nakong ea bophelo ba pele ho bophelo ho ka lebisa phetolelong e telele ea sistimi ea moputso, e tlohelle setho se le kotsing eseng feela bakeng sa litloaelo tse mpe tsa ho ja empa mohlomong le mathata a mang a tsamaiso ea moputso.

lumela hore baa fokola

Re leboha K. Carlin ka thuso ea ho ikatisa ka liphoofolo le ho alima. Mosebetsi ona o tšehelitsoe ke The University of Pennsylvania Institute of Diabetes, Obesity, and Metabolism, DK019525.

Lethathamo la Maqakabetsi

  • P
  • letsatsi la pelehi
  • Cdk5
  • cyclin e itšetlehileng ka kinase 5
  • DARPP-32
  • dopamine le cyclic adenosine monophosphate e laoletsoeng phosphoprotein, boima ba molek'hule 32 kDa
  • Monate
  • threonine
  • NPY
  • neuropeptide Y
  • POMC
  • pro-opiomelanocortin
  • DA
  • dopamine
  • E
  • letsatsi la embryonic

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.

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