Tlhaloso e Tšoarellang ea Opioid e sa Lebelloang e Tšoanang le ea ho ja Lijo-Ho ja Lijo Tse Nang le Lijo Tse Fokolang Lijo Tse Hahiloeng ka ho Fetisisa (2007)

Keywords:

ho itlopa bolutu, ho ba le phihlelo e fokolang, ho noa lijo kapa ho fepa, ho nona haholo kapa ho ba motenya haholo kapa ho ba le botenya haholoanyane, μ opioid-receptor kapa κ mohanyetsi oa li-opioid-receptor, bulimia OR bulimic, mafu a ho ja, matšoenyeho, ghrelin, leptin, hormone ea ho hōla, likhoto tsa basali

SELELEKELA

Ho itlopa joala ke boitšoaro bo sa tloaelehang ba ho fepa bo khetholloang ke lijo tse tloaelehileng, tse feteletseng. Likokoana-hloko, likarolo tsa ho hlahloba mathata a 'maloa a ho ja, hangata li akarelletsa lijo tse monate tse nang le tsoekere le mafura le' tahlehelo ea taolo '(Mokhatlo oa Mahlale oa Amerika, 2000; Corwin le Buda-Levin, 2004; Yanovski, 2003). Ho ja lijo tse ngata ho atile haholo ho batho ba mafura haholoanyane, empa, ka lehlakoreng le leng, ba jang joala ba atisa ho ba boima haholo (Pike et al a, 2001; Smith et al a, 1998). Ka lebaka leo, ho itlopa joala ke tšoaetso e kotsi ea bothata ba botenya haholo (Hudson et al a, 2007). Taba e kholo pakeng tsa ho ja lijo tse ngata le dysphoria e 'nile ea hlokomeloa' me boemo ba tlhaho ba kamano ena ha boa tsitsa (Blazer et al a, 1994; Gluck, 2006).

Mehlala ea kajeno ea ho ja lijo tse ngata e hatisa bohlokoa ba ho thibela lijo ho ntlafatsa boitšoaro ba ho itlopa joala (Howard le Porzelius, 1999), le mefuta e mengata ea liphoofolo e hlahisang hore histori ea lijo tse thibelang lijo, e behoa ka ho fokotsa khalori ea letsatsi le letsatsi (mohlala 66% ea ho ja lijo tsa letsatsi le leng le le leng) (Hagan et al a, 2003) kapa nako ea ho fumana lijo letsatsi le letsatsi (mohlala 2 h) (Inoue et al a, 2004), ke bohareng ba ho itlopa joala. Leha ho le joalo, mokhoa o mong oa ho nahana o ka 'na oa totobatsa tšobotsi ea boleng ba ho thibela lijo, e leng ho leka ho khaotsa ho ja lijo tse tsoang lijong tse thibetsoeng,Kales, 1990; Knight le Boland, 1989; Fletcher et al a, 2007; Mitchell le Brunstrom, 2005; Gonzalez le Vitousek, 2004; Mahlomola le Maheberu 2004; Corwin, 2006; Corwin le Buda-Levin, 2004). Batho ba jang joala ba thibela lijo tsa 'ho thibela' ho fihlela 'ho khutlela' lijo tse fokolang ho fokolloa feela, hangata ho tloaelehile, ho ba le mekhahlelo ea liaparo, mohlomong ho thibeloa ke thibelo e matla ea matla.

Ho tloaelehile hore ho be le lijo tse thibetsoeng ho phekola lipepa tsa 'thibelo,' tebello ea (ho hlakanyetsoa ka nako e hlakileng) le lijo tse natefisang, tse lebisang ho hana mekhoa e meng e amohelehang ho batho, e hlalosoang ke ba bang e le ho fokotsa (Pliner et al a, 1990). Phetoho e joalo ea ho amoheloa ha lijo e ka eketsa kotsi ea ho fokotsa 'mele le mathata a ho ja ka lebaka la karolo e eketsehileng e behiloeng ho sensory-hedonic, ho e-na le phepo e nepahetseng, thepa ea lijo bakeng sa ho noa lijo (Wardle et al a, 2001). Mohlomong analog ea phetoho ena e ithutoang ka ho amoheloa ha lijo, phapang e fosahetseng ka litoeba e bua ka hypophagia ea ntho e amohelehang ka tsela e sa amohelehang e bakoang ke ho ba le phihlelo ea ho fumana ntho e itseng e khethiloeng hang-hang pele (ho latellana hampe) kapa ho latela phapang) ntho eo (Flaherty le Checke, 1982; Flaherty le Rowan, 1986; Flaherty et al a, 1995). Litlamorao tsa phapang li ithutiloe pejana ho sebelisoa tharollo e fumanehang ka mokhoa o fokolang (3-5 min) tharollo ea likhoto tse thibetsoeng ka boima ba 'mele, empa ha li so ka li ithutoa hantle ho amohela lijo le ho li ja ka lithuto tse ithutoang. ho beha boima ba mmele.

Ka hona, bobeli ba ho ja le ho hana ho fokolloa haholo, empa mohlomong lijo tse ling li ka 'na tsa emela mekhoa e tloaelehileng ea ho itšoara ka tsela e fapaneng le ho ba le phihlelo e fapaneng le ea lijo ho feta nako. Nakong e fetileng, liketsahalo tsena li 'nile tsa aroloa likarolong tse fapaneng tsa thuto' me ha li nahane ka hore na li amana joang. Thuto ea hona joale e ile ea leka ho leka khopolo ea hore likhoho tse nang le phihlelo e fokolang ea lijo tse khethiloeng li ne li tla hlaolela ho ja lijo tse tloaelehileng le ho lebella ho fapana ha maikutlo, kapa hypophagia, e seng e amohelehang, pele ho lijo. Ka hona, sepheo se seholo sa thuto ena e ne e le ho leka khopolo ea hore ho itlopa joala le ho lebella ho fapana ho sa tšoaneng ho na le liketsahalo tse kopantsoeng le metso e arolelanoeng ea etiologic, joalokaha ho bontšitsoe ka morao ho fihlella ha lijo tse monate.

Sepheo sa bobeli sa thuto e ne e le ho lekola khopolo-taba e khethollang μ/κ Mohanyetsi oa li-opioid-receptor o ne a ka fokotsa feela ho ja lijo-thollo tse kang ho ja lijo tse ratoang haholo, empa hape ho fapana ka mokhoa o fapaneng oa ho ja lijo tse sa ratoang ho latela histori ea lijo. Nalmefene o ne a bolelloa ho tloaela ho ja lijo tse latellanang ka tsela e fapaneng, ho fokotsa ho ja lijo tse ling tse sa kang tsa e-ba le khetho ea lijo, empa ho nkoa ho eketseha ha lijo tse sa ratoang tse hlahang lijong tse nang le phihlelo. Tlaleho ena ea bobeli, ho bolela esale pele ho thehiloe ho se fumanoeng (1) ho ja lijo le ho lebella ho fapana ha maikutlo ho fosahetseng ke ho feto-fetoha ho bakoang ke boitšoaro (Corwin, 2006; Flaherty et al a, 1995) le hore (2) bahanyetsi ba li-opioid-receptor ba fokolisa mekhoa e amanang le palatability (Cooper, 2004; Li-geom le Grey, 2002).

Sepheo sa boraro sa merero e hlalosang e ne e le ho hlalosa boitšoaro bo amanang le ho tšoenyeha le liphello tsa ts'ebetso ea likhallelo tse fokolang, tse fokolang haholo ho fumana lijo tse tsoekere, tse nang le phepo tlas'a maemo a hona joale a liteko. E le ho fumana hore na litoeba tse fumanoang li fumaneha hakaalo lijong tse khethiloeng li ile tsa eketseha ho tšoenyeha-joaloka boitšoaro, lihlooho li ile tsa lekoa ho feta-maze. Ho fumana hore na litoebe tse nang le histori e joalo ea lijo li ne li ka 'na tsa e-ba boima haholo, liphetoho tse atlehang ho fepa, boima ba' mele, bohlasoa, le ho potoloha leptin, 'ghrelin' e mafolofolo, le li-hormone tsa ho hōla (GH) li ne li lekantsoe.

LISEBELISOA LE MEKHOA

Lihlooho

Mosali ea lilemong tsa bocha ea bitsoang Wistar,n= 23 126-150 g, matsatsi a 41-47; Nōka ea Charles, Raleigh, NC) e ne e le masoabi-e le ho fihla ka mahare a polasetiki (19 × 10.5 × 8 inches) ka 12: 12 h lit (mokoloko o potolohileng, 0800 e khantša), mongobo- (60% ), le ho laola mocheso (22 ° C) vivarium. Li-rats li ne li fihlella li-rodent chow (Harlan-Teklad LM-485 dijo 7012: 65% (kcal) lik'habohaedreite, 13% fat, 21% protein, 3.41 kcal / g; Harlan, Indianapolis, IN) le metsi ad libitum bakeng sa beke ea 1 pele liteko. Mekhoa e tsamaisitsoeng le Mekhatlo ea Sechaba ea Bophelo bo Botle bakeng sa tlhokomelo le tšebeliso ea liphoofolo tsa liphoofolo (NIH Publication nomoro 85-23, e ntlafalitsoeng 1996) le 'Melao-motheo ea tlhokomelo ea liphoofolo tsa laboratori' (http://www.nap.edu/readingroom/bookslabrats) mme ba amoheloa ke Komiti ea Institutional Animal Care le Komiti ea Ts'ebetso ea Scripps Research Institute.

Lithethefatsi

Nalmefene hydrochloride, kapa 17- (cyclopropylmethyl) -4,5α-epoxy-6-methylenemorphinan-3, 14-diol hydrochloride (Mallinckrodt, St Louis, MO) e ne e se e qhibilihile ka saline ea isotonic. Nalmefene e tlama ka hloko ho κ (K_i= 0.083 nM) le μ (K_i= 0.24 nM) li-receptor subtypes, empa ~ 2 e laela ka tlase ho δ, ho feta ho μ or κ, receptors (K_i= 16.1 nM). Ka lebaka leo, motho ea nang le bokooa o na le mohanyetsi ea phahameng oa mohanyetsi κ 'me μ (KEA BONA₅₀= 18.5 le 13 nM, ka ho latellana), empa tlase joalo δ, subtypes (Bart et al a, 2005; Culpepper-Morgan et al a, 1995; Emmerson et al a, 1994; Michel et al a, 1985).

Khetho ea lijo

Ho fumana khetho ea phepo e nepahetseng, litoeba tsa acclimated (n= 8) li fanoe ka mokhoa o ts'oanang oa lijo tsa chow le lijo tse nang le phepo e nepahetseng, ea chokolete, e phahameng-sucrose (50% kcal), lijo tse thehiloeng ho AIN-76A tse ts'oanang le tse ling tse nang le mefuta e meholo le matla a matla a lijo (chocolate-flavored formula PJPPP: 69.1% (kcal) lik'habohaedreite, 11.8% mafura, 19.1% protheine, matla a metaboliza 3.70 kcal / g; e hlophisitsoeng e le 45-mg e nepahetseng ea lijo tsa pellets ho eketsa khetho ea eona, Cooper le Francis, 1979;; Lipatlisiso tsa Lipatlisiso Inc., New Brunswick, NJ) (bona Lethathamo 1). Ka mor'a ho ja lijo le ho rata lijo, lijo tsa lijo li ne li hakanngoa e le karolo ea% ea kakaretso ea 24-h (kcal) e sebelisoang ka mokhoa oa ts'ebetso ea chokolete e phahameng ea sucrose, e fumanoang e khethoa haholo ka lihlooho tsohle ( sheba Liphello) le seo mona ka mor'a moo ho thoeng ke 'lijo tse khethiloeng'.

Hypothesis 1:

Ho fapana ho sa tsotelleng ha lintho tse mpe le ho ja lijo tse kang ho itlopa joala ho hlahella hammoho.

Mokhoa oa ho fepa

Baseline

Sehlopha se seng sa thuto (n= 15) e ne e lumellane le lenane la tlhahlobo la letsatsi le leng le le leng la tlhahlobo ea liteko: 15 min pele ho qala ho potoloha ha lefifi, liphoofolo li isoa ka kamoreng, li lekanngoe, 'me ka bomong li kenngoa ka mekhoa ea khoele (20 × 25 × 36 cm). Lenaneo le leng le le leng la liteko le ne le e-na le linako tse 'nè tse khotsofatsang ka mokhoa o latelang: (a) 1-h chow ho fumana, (b) 2-h ho amoheloa lijo, (c) 10 ho fihlella ho lijo tsa chow, le (d) 10- ho fihlella ho fapaneng ea lijo tse fapaneng. Ka nako eo likotla li ne li khutlisetsoa kahare ea lehae le vivarium e nang le chow e fumanehang ad libitum. Nakong ea motheo le tlhahlobo, metsi a ne a lula a le teng ad libitum. Lerata le letšo (70 dB) le ne le le teng kamoreng ea teko. Lefu la 2-h le hlokahalang (1) le etsa seaparo sa morao-rao, (2) ho eketsa mofuthu oa ho ja, (3) ka nako e khutšoanyane ea tlhahiso ea motheo ea 10 le ho satiation e latelang, le (4) ho fana ka bopaki ba ho fumaneha ho haufi lijo tse khethiloeng. Tlhahlobo e ne e lekanngoa le 0.01 g e nepahetseng. Mokhoa o nepahetseng oa ho fepa o ne o nkoa e le phaello ea 'mele (mg) ka unit (kcal) matla a ho kenya matla. Ho feta libeke tse 'nè tsa 2, lijo tse tsoang ho 10-miners feeders li tsitsitse, ka ho fepa ka lekhetlo la pele ka nako e tloaelehileng ea ho ithuta ho fumana matsatsi a mangata r=0.97, p<0.01) (Hartz et al a, 2001). Nako ena ea motheo e arohane le nako ea ts'ebetso ea ho fumana liphallelo / liphallelo ho tloha ho khethollo ea lijo ea ho ja lijo tse khethiloeng.

Testing

Bakeng sa liteko, likhoto, tse lekaneng bakeng sa boima ba 'mele, lijo tsa letsatsi le leng le le leng, phepo ea phepo, le ho ja lijo nakong ea nako ea tlhahlobo ea lihlopha, li abeloa sehlopheng sa ho laola' chow / chow ', se amohelehang ho tsoa ho ba febeli ba metsotso ea 10 kapa 'chow / sehlopha se khethileng', se ileng sa amoheloa lekhetlo la pele motseng oa pele oa 10, empa ho e-na le hoo se fumane lijo tse khethiloeng motseng oa bobeli oa 10-feed. Li-rats li ile tsa hlahlojoa letsatsi le leng le le leng ho fihlela letsatsing la 52, ntle le ha ho boleloa ka hosele

Hypothesis 2:

Li-rats tse nang le li-intermittent, tse fokolang haholo ho fihlella lijong tsa tsoekere, tse ratoang li tla bontša ho eketseha ho tšoenyeha-joaloka boitšoaro.

Boholo bo boholo ba bo-maze

Ho fumana hore na litoeba tse nang le phekolo e fokolang ea lijo tse khethiloeng li ile tsa eketseha ho tšoenyeha-joaloka boitšoaro, tlhahlobo e phahameng ea bo-maze e ile ea etsoa tlas'a khanya e khanyang joalokaha ho hlalositsoe pele (Zorrilla et al a, 2002). Mehato e ka sehloohong e ne e le karolo ea palo ea nako eohle ea letsoho le lipolelo tse lebisitsoeng matsohong a sabaletseng, ho netefalitsoe boitšoaro bo amanang le ho tšoenyeha (Fernandes le File, 1996) le palo ea litlhaloso tsa letsoho tse koetsoeng, letšoao la mosebetsi oa ho holisa (Cruz et al a, 1994). Lipotlolo tse hlalositsoeng ka khopolo-taba 1 li ile tsa lekoa 3-5 h ho potoloha lefifi (~ 24-26 h ka mor'a hore motho a fumane lijo tsa pele pele) nakong ea tlhahlobo ea 16. Seboka sa kamehla se fepa ha sea ka sa etsoa letsatsing lena.

Hypothesis 3:

Phekolo ea meriana e tla fapana ka tsela e fapaneng le ho ja lijo ho latela histori ea lijo.

Ho fumana hore na mosebetsi oa opioid receptor o phetha karolo efe ka likamano tsa ho fepa ka makhethe, likokoanyana li fumanoe li-nalmefene (0, 0.01, 0.03, 0.1, 0.3, 1 mg / kg, ka tlaasana (sc)) 20 min pele pele ho metsotso ea 10. Lekhetlo lena la ho itšireletsa le ile la khethoa ho tiisa mosebetsi o feletseng oa bahanyetsi ho pholletsa le pontšo ea ba fepa ka bobeli. Litlaleho tse fetileng li bontša hore ho nka 15-20 min bakeng sa phello e phahameng ea litšepe tse tlaase ho hlokomeloa ho rat, e nang le liketsahalo tse tšoanang le tse sebetsang le Ex vivo bolulo bo amohelehang bo bolokiloe bonyane 1 h (June et al a, 1998; Unterwald et al a, 1997; Moholo oa ntlo et al a, 1992). Litlhare li ne li fuoa likhofu tse hlalositsoeng ka khopolo-taba ea 1 li sebelisa sebopeho se feletseng sa square Latin le 1 ho 3 matsatsi a tlhahlobo a sa sebetseng kalafo ho tloha matsatsing a 24 ho ea 37 ho latela liente tse tharo tsa letsatsi le letsatsi tsa acclimating saline.

Hypothesis 4

Li-rats tse nang le li-intermittent, tse fokolang haholo ho fihlella lijo tse tsoekere, li tla ja haholo.

Ho potoloha leptin, GH, le 'mafolofolo' ghrelin

Ho fumana hore na litoeba tse nang le phetoho e fokolang ea lijo tse khethiloeng li na le liphetoho tse ngata tsa fatše le mafura tse bonngoeng ka botenya, likhofu li ne li jeoa ka makhetlo a mabeli (18 h) 'me li fokotseha 2-5 h lefats'eng le lefifi ka mor'a matsatsi a 53 lijong tsa lijo. Li-rats li ile tsa bolaoa ka mor'a seaparo sa 18-h se le seng se lekaneng ho fokotsa ho ka senya liphello tse matla tsa phepo, ho kenyelletsa le lijo tse amanang le histori historing ea ho noa nakong ea ho fepa ha liteko kapa matlong a lehae. Ho fokotsa likhoto 'ho potoloha ho sa sebetse, boholo ba ho itima lijo e ne e le boikokobetso ka lebaka la lik'halori, ho bapisoa le ba sebelisitsoeng pele ho ithuta lintlha tsena tsa endocrine ka likhoto (Proulx et al a, 2005; Drazen et al a, 2006) 'me e tšoana le mekhoa ea kliniki ea ho itima lijo bosiung bo lekaneng ho lekanya lihomone tsena ho batho (Falorni et al a, 1998; Sherwin et al a, 1977). Mali a kutu (~ 5 ml) a ile a bokelloa ka lipompong tse batang tse nang le 500 μl ea 0.5 M ethylenediaminetetraacetic acid le 50 μl ea khoebo ea protease inhibitor cocktail (Sigma catalog P8340). Lero la mali le ne le arotsoe ke centrifugation (4 ° C, 3000 g, 15 min) le ho bolokiloe ho -80 ° C ho fihlela tlhahlobo e hlakileng ea li-immunoassays bakeng sa rat leptin (LincoPLEX), GH le Ser³-n-octanoylated ghrelin (acyl-ghrelin) e amanang le enzyme e amanang le immunosorbent assay (Linco, St Charles, MO). Meeli ea sensitivity e ne e le 12, 500, le 33 pg / ml, ka ho latellana. Li-coefficients tse tloaelehileng tsa "intra-assay" tsa mefuta-futa ke <5, <4, le 3.5-5.5%, ka ho latellana.

Boemo

Litopo li ne li thawed (mocheso oa kamore) ebe li lekanngoa ho fumana hore na metsi a lahleheloa ke metsi afe. Lipampitšana tsa menoana li ile tsa tlosoa ho bona hore na boima ba 'mele bo hokae. Inguinal (subcutaneous) le gonadal (intra-mdom / visceral) liphahlo tsa fatše li ne li arohanngoa, li lekanngoa, ebe li khutlisetsoa setulong sa lik'hemik'hale tlhahlobo. Kakaretso 'mele oa metsi, mafura a mafura le mafura a se nang mafura (FFDM) a ne a ikemiselitse ho sebelisa mokhoa oa Harris le Martin (1984).

Tlhahlobo ea Litekanyetso

Liphetoho lenaneong la liteko tsa ho ja lijo le ho bokella phepelo ea phepelo li ile tsa hlahlojoa ho sebelisoa litlhahlobo tse peli tsa covariance, ka mantlha e le covariate. Keketseho ea ho ja lijo tsa letsatsi le letsatsi le boima ba 'mele li ile tsa hlahlojoa ho sebelisoa mehato e pheta-phetoang ea litekanyo tsa phapang (ANOVA) Mefuteng eo ka bobeli, nalane ea lijo e ne e le sesosa se pakeng tsa lihlooho le letsatsi e le karolo ea lihlooho. Seithuti t-e ne e sebelisetsoa ho hlalosa liphapang tsa sehlopha sa bohlokoa le ho khetholla liphetoho tse amanang le ho ja lijo le boima ba 'mele.

Ho fumana hore na 'ho fumanoa' ho fepa ho fapana le lijo (Hagan le Moss, 1997) le ho ba le phapang e sa lebelloang e fapaneng (ea pele ea ho fepa hypophagia) e tšoanang le mokhoa oa ho ithuta oa ho kopanya, ho latela mokhoa o latelang oa ho fetola mokhoa oa boipheliso o ne o tšoanela ho fepa (Hartz et al a, 2001):

Mokhoa o fokolang oa motsoako le o motlakase o noa ka pele le ka asymptotic ka mor'a phepo ea ho fetola boitšoaro bo bakoang ke histori ('learning'). The Hillslope e hlalosa tekanyo le valence ea mekhoa e metle ea ho itekanya. The EC₅₀ e hlalosa palo ea matsatsi a fetisitsoeng ho fihlela 50% ea phetoho e kholo ea boitšoaro e etsahetse.

Ho etsa qeto ea hore na litoeba li fapane ka tsela e fapaneng joang le maemo a bona a ts'oaetsanoang ka ho lebella phapanyetsano e mpe kapa ho ja lijo tse peli, mekhoa e 'meli,Shrout le Fleiss, 1979) li ne li etsoa ka lekhetlo la pele le la bobeli la 10-feed feed (kcal) ea matsatsi a 7 ho 15.

Ho fetoha ha linomoro ho ne ho sebelisetsoa ho bona hore na litoeba tse nang le phihlelo e fokolang ea lijo tse khethiloeng li bontšitse tloaelo e fetohileng (r², sebopeho sa mefuta-futa e hlalosoa) kapa tlhaho (maralla) ea kamano pakeng tsa lijo tsa pele le tsa bobeli tse kenang lijong. Tlhekefetso e ne e boetse e sebelisetsoa ho hlahloba kamano pakeng tsa boholo ba 'binge' (e leng lijo tse bolelang 'mele oa 2 ho tloha matsatsing a 7-15) le boitšoaro bo kang ba ho tšoenyeha, ka tsela e fapaneng e lekantsoeng ke ho kena ka letsoho.

Litholoana tsa Nalmefene lijong li ile tsa hlahlojoa ho sebelisoa mehato e pheta-phetoang ea li-ANOVA. Nalane ea lijo le tekanyetso li ne li le lipakeng tsa- le kahare ho lihlooho tsa litaba, ka ho latellana. Phapang e fapaneng e ile ea etsa qeto ea hore na litlamorao tsa litekanyetso li ne li its'etleha ka log, hape le nalmefene's ED₅₀ ho fokotsa phepelo ea bobeli ea phepelo (ho ja joalo ka binge) ho hakantsoe ho sebelisa ts'ebetso e kaholimo ea sigmoidal dose. Litlamorao tsa tekanyetso ea lipara li ile tsa tolokoa ho sebelisoa liteko tsa Dunnett le litla-morao tsa nalane ea lijo ke tsa Baithuti t-liteko. Teko ea Dunnett e ne e sebelisetsoa ho fumana hore na nalmefene e tloahelehileng ho ja likhoto tsa chow / tse fepiloeng ka mokhoa o khethiloeng ho maemo a fuoang koloi / chow-fed.

Ho lekola tlhaloso ea hore hypophagia ho feeder ea pele e kanna ea bontša karabelo ea puseletso ho boima bo fetelletseng ba 'mele, likopano tsa Pearson li baliloe ka metheo e nang le likarolo tse tšeletseng le tse lahliloeng ka matsatsi a 7-15. Liphuputso tsena li ile tsa etsa qeto ea hore na ho na le kamano e fapaneng pakeng tsa liphapang tsa boima ba 'mele ka lehlakoreng le leng ka nako e le' ngoe (ka letsatsi le le leng) kapa ka mor'a moo (e lagged ke matsatsi a 1 kapa a 2) phapang ea phepelo ea pele ea hypophagia (e amanang le motheo) ho e 'ngoe. Likamano li ile tsa etsoa ka mokhoa o bohlale ka letsatsi, ka karolelano ho latela ea Fisher Z liphetoho le ho khutlisetsoa morao ho fumana karolelano r. Ka lebaka la ho se tsitsane ha likamano tsa letsatsi le letsatsi, litlhahlobo li boetse li sebelisetsoa ho lumellana le karolelano ea letsatsi ea 3 ea boima ba 'mele ea' mele ka karolelano ea matsatsi a 3 a tsamaeang a chow hypophagia.

Boikarabello, metabolite ea plasma / methapo ea lihormone, le litekanyo tsa ma-maze li ile tsa hlahlojoa ho sebelisoa Liithuti tse sa sebetsaneng kapa tse kopaneng. t-a bapisoa le lihlooho tse pakeng tsa kapa tse ka hare, ka ho latellana. Lipapali tsa software li ne li le Systat 11.0 (SPSS, Chicago, IL), SigmaPlot 9.0 (Systat Software, Inc., Point Richmond, CA), InStat 3.0 (GraphPad, San Diego, CA) le Prism 3.0 (GraphPad).

LIPOTSO

Khetho ea lijo

Se bolelang (± SEM) sekhahla sa khetho ea 24-h (kcal) bakeng sa lijo tse hahiloeng ka tsokolate tse khethiloeng ka mokhoa o tšoanang, ka lebaka la lijo tsa chow e ne e le 92.2 ± 1.1% (moeli: 88.8-97.9%).

Hypothesis 1:

Ho fapana ho sa tsotelleng ha lintho tse mpe le ho ja lijo tse kang ho itlopa joala ho hlahella hammoho.

Sequential 10-Min Feeders

Joalokaha ho boletsoe esale pele, likhofu tse fumanoang li fumaneha haholo lijong tse khethiloeng (chow / khethiloeng) li thehiloe hypophagia ea chow ho tloha pele ho 10-feeder (Setšoantšo sa 1a;; histori ea lijo: F (1,12) = 14.48, p<0.005; nalane ea lijo × letsatsi: F (14,168) = 2.29, p<0.01) le hyperphagia ea lijo tse khethiloeng ho tsoa ho feeder ea bobeli ea 10-min (Setšoantšo sa 1b;; histori ea lijo: F (1,12) = 53.96, p<0.001; nalane ea lijo × letsatsi: F (14,168) = 8.98, p<0.001). Ho ikatisa ka mokhoa oa phepelo ho ne ho ipapisitse le boiphihlelo, joalo ka ha ho bonts'itsoe ke nalane ea lijo × litšebelisanong tsa letsatsi mme, haholoholo ka mokhoa o motle oa ho noa ho tsoa ho e mong le e mong ho ea ts'ebetsong ea boithuto bo amanang le sigmoidal (Setšoantšo sa 1c, Lethathamo 2). Mekhoa ena e 'meli e ne e se feela litsela tse sa tšoaneng, empa le mekhoa e fapaneng ea lithuto le nako. Ho fumanoa ka ho ja lijo tse nang le ho itlopa joala (ho fepa 2) ho fetisitse mme ho etelle pele ho ea chow hypophagia (ho fepa 1 lijo). Lijo tsa lihlopha tsa histori li ne li fapane ka ho latellana ka letsatsi 2 bakeng sa lijo tse fanang ka 2 (ho khethoa ha hyperphagia), empa ho fihlela letsatsi la 9 bakeng sa ho ja 1 lijo (chow hypophagia). The EC₅₀ bakeng sa ho itlopa joala ho tšoana le hyperphagia pele ho seo bakeng sa 'ho lebella' letsatsi la 4-5 (chow hypophagia)Lethathamo 2).

Le hoja likhoho tse fepehileng / chow tse neng li fepehile li ne li batla li lekanngoa ke motsoako oa pele oa ~ 6 kcal, tse bontšang ho ja haholo (~ 1 kcal) ho tloha ho fepa ka bobeli (Setšoantšo sa 1b), litoeba tse fepehileng / tse fepehileng li ile tsa eketsa lijo tsa bobeli tse ntseng li fepa ka bongata ba bohlokoa ba 34.4 kcal. Ka hona, 42.9 ± 2.0% ea lijo tsa bona tsa letsatsi le leng le le leng (kapa 45.6 ± 2.7% ea lijo tsa letsatsi le letsatsi) li ne li sebelisoa ka har'a 10 min feela ka tekanyo ea e le 'ngoe ea 45 mg pellet ea lijo e' ngoe le e 'ngoe 2.9 ± 0.1 (lebotho: 151-259 pellets / 10 min). Ka lehlakoreng le leng, tlhahiso ea pele ea lijo ea lijo e ile ea fokotseha ho ea ho 3.4 kcal (61% ea motheo oa ho qala ho fepa).

Palo ea boima ba 'mele le pele ea ho iphelisa ka hypophagia

Makhoeng a khefu / a ratang, boima bo bongata ba 'mele ha boa ka ba bolela esale pele hore hypophagia ea pele e tla feta ho feta ho tloha matsatsing a 7-15, joalokaha ho bontšoa ke ho haelloa ke sepakapaka se nang le meeli e mengata r= 0.102) kapa likamano tse sepakapakeng pakeng tsa mehato ena (karolelano r's = 0.022 le -0.040 bakeng sa li-lags tsa 1- le 2-day, ka ho latellana). Ka mokhoa o ts'oanang, boima ba 'mele ba boima ba' mele nakong ena bo ne bo sa amane le boholo ba eona ba "feeder hypophagia" (karolelano r= -0.025).

Phapang ka bomong le tlhahlobo ea correlation

Ho fapana le ho haelloa ke kamano ea boima ba 'mele ho ea pele ho fepa hypophagia, tlhahlobo ea intraclass analysis e bontšitse matla, a tsitsitseng ho arohana ha motho ho kenngoa ha lipoe tse khethiloeng ho tloha ho tse peli tsa pele (ICC[2,9] = 0.86, r²= 0.74; F (7,56) = 7.93, p<0.00001) le feeder ea bobeli (ICC[2,9] = 0.89, r²= 0.79; F (7,56) = 9.42, p<0.00001). Ka lehlakoreng le leng, likhoto tsa chow / chow tse fepehileng ha li bontše phapang pakeng tsa tlhahiso ea lijo tsa pele (ICC[2,9] = 0.37, r²= 0.14; F (6,48) = 1.61, p= 0.17) le mefuta e fokolang ea batho ka bobeli ka ho kenngoa ha lijo (ICC[2,9] = 0.64, r²= 0.41; F (6,48) = 2.78, p<0.05). Kahoo, kamora bohloki bo bobebe, likhoto tsa chow / chow tse fepehileng li ile tsa hana ka mokhoa o batlang o ikemetse ka litšobotsi tse ikhethileng tsa motho ka mong. Ka lehlakoreng le leng, likhoto tsa chow / tse fepehileng ka mokhoa o khethiloeng li bontšitse litšobotsi tse kang tsa batho ba 'lebelletseng' chow hypophagia le lijo tse khethiloeng tsa hyperphagia kamora thibelo e bobebe ea matla.

Le hoja litoeba tse feptjoang ka ho khetheha li ne li sebelisoa haholo ebile li tsamaisana hantle le batho ba fepa (slope = 0.78, e kholo ho feta 0, F (1,5) = 11.67, p<0.02), e tsamaellanang le tlatsetso e tsitsitseng, ho ne ho se na khokahano e tšepahalang lipakeng tsa ho jeoa ha likhoto tsa chow / tse fepehileng ka ho khetheha ho tloha ho chow ho ea ho fepa lijo (moepa o sa tsejoeng ho tloha 0, F (1,6) = 1.07, p= 0.34) (bona Setšoantšo sa 1f, phapang ho r², z= 2.43, p= 0.01]). Ka hona, ho kenngoa ha lipoe tse khethiloeng ka ho khetheha ha hoa ka ha e-ba le tšusumetso e ntle kapa e fokolang ea matla a 'mele homeostatic / compensation' nako e khutšoanyane ho lijo / fepa. Lihlooho tseo tse bontšitseng hore ntho e matla ka ho fetisisa e lebelloang ke hypophagia e ne e se eona e neng e le eona e bontšang li-hyperphagia tse kholo ka ho fetisisa.

Predeprivation 1-h ho noa lijo

Predeprivation 1-h ho noa lijo tsa likhoho tse fepehileng li ne li boetse li hatelloa haholo ho tloha letsatsing la tlhahlobo 11 (Setšoantšo sa 1d;; histori ea lijo tsa lijo × letsatsi ho sebelisana F (14,182) = 2.35, p<0.01). Leha ho le joalo, phokotso ea tlhahiso-pele ea li-chow tsa 1-h e ile ea qala hamorao (letsatsi la 11 vs Letsatsi la 9) le tse nyane haholo ka bobeli (t(7) = - 5.59, p<0.001) le motheo o lekanang (t(7) = - 3.00, p<0.01) ho feta phokotso ea karolelano ea phepelo ea pele ea phepelo e bonoang ka likhoto tsa chow / tse khethiloeng. Habohlokoa, liphuputso tsena li tsamaellana le tlhaloso ea 'tebello' ea phepelo ea pele ea phepelo ea 'mele' me, joalo ka ho ba sieo ha likamano le boima ba 'mele, ho sa lumellaneng le tlhaloso e ngoe ea hore hyperfhagia ea pele e fuoang ke likarabo tse setseng tsa matla a homeostatic ho fepa pele kapa ho nona haholo phaello.

Home-cage chow ho ja

Lehae la lehae la cage-cage ho ja likhomo tse ratoang haholo-butle-butle li ile tsa theoha butle-butle ka mokhoa o itšetlehileng ka phihlelo (Setšoantšo sa 1;; histori ea lijo: F (1,12) = 100.64, p<0.001; nalane ea lijo × letsatsi: F (14,168) = 12.06, p<0.001), haholo joalo ka letsatsi la 3 la liteko.

Kakaretso ea lijo tsa letsatsi le letsatsi

Leha ho na le liphetoho tse kholo phepong ea lijo tse khethehileng ka letsatsi, ANOVA ha ea ka ea senola litlamorao tse kholo tsa nalane ea lijo kapa nalane ea lijo × letsatsi ka keketseho ea phepelo ea matla a letsatsi ka leng. Leha ho le joalo, ea Student t-botho ba bontšitse hore matla a mangata a ho kenngoa ha matla a likhomo tse khethiloeng ke khefu / a khethiloeng a batla a fokotseha hanyenyane, empa haholo-holo, a fetisitsoe ho feta likhoho tse fepehileng / chow tse qalileng ho tloha letsatsing la tlhahlobo 9 (Setšoantšo sa 1g).

Hypothesis 2:

Li-rats tse nang le li-intermittent, tse fokolang haholo ho fihlella lijong tsa tsoekere, tse ratoang li tla bontša ho eketseha ho tšoenyeha-joaloka boitšoaro.

Likarolo tse khethiloeng tse khethiloeng ke Chow / tse khethiloeng li bontšitse ho fokotseha ha nako e khutšoanyane ka hare ho (Setšoantšo sa 2a, ho le letšehali) le ho kena ho (ho bolela ± SEM: 21.5 ± 4.6 vs 34.7 ± 4.7%; t(13) = 2.14, p<0.05) matsoho a bulehileng a "maze" e phahameng ha e bapisoa le likhoto tsa chow / chow tse fepehileng, phello e kang ea khatello ea maikutlo. Palo ea likenelo tse koetsoeng tsa letsoho, tekanyo ea taolo ea ts'ebetso ea motlakase (Cruz et al a, 1994), e ne e sa fetohe ka histori ea lijo (Setšoantšo sa 2a, ka ho le letona). Boholo ba khoto bo tloaelehileng ba 'ho itlopa joala' bo hokahane ka matla le boemo ba eona ba boitšoaro bo ts'oenyehileng, bo bonts'itsoeng ka khokahano e kholo e pakeng tsa karolelano ea fepa ea 2 le% ea nako e bulehileng ea letsoho ho likhoto tsa chow / tse fepehileng (Setšoantšo sa 2b). Kamano ena e bile le phapang e kholo ea mehato ena (77.4%) 'me e ne e se ea bohlokoa ha ho hlahlojoa likhoto tsa chow / chow ho sa tsotellehe hore na e ka ntle e ne e kenyelelitsoe (36.5%) kapa e arotsoe (9.2%).

Hypothesis 3:

Phekolo ea meriana e tla fapana ka tsela e fapaneng le ho ja lijo ho latela histori ea lijo.

Tlas'a maemo a tšoaroang ke likoloi, likhoto tse fepehileng / tse fepehileng li ne li bontša 'ho lebella' chow hypophagia (feeder 1) le ho khethoa ha hyperphagia (feeder 2) (Setšoantšo sa 3). Joalokaha ho boletsoe esale pele, phekolo e fokolang e ile ea ama ka tsela e fapaneng ea 10-min chow e tsoang ho ea fanang ka lijo ho latela histori ea lijo (ho ja lijo historing / dose: F (5,65) = 3.60, p<0.01; lethal dose: F (5,65) = 3.06, p<0.05). Haholo-holo, nalmefene e fokotse ho ja ha likhoto tsa chow / chow tse fepehileng ka mokhoa o ts'oanang, o itšetlehileng ka tekanyetso (F (1,30) = 13.35, p<0.001), ka liphokotso tsa bohlokoa tse tsoang koloing tse hlokometsoeng litekanyong tsa 0.03 le 1 mg / kg. Ka lehlakoreng le leng, nalmefene e ekelitse haholo ho ja chow ea likhoto tsa chow / tse fepiloeng ka mokhoa o khethiloeng ka tekanyo ea 0.03 mg / kg (Setšoantšo sa 3, ho le letšehali). Ka lebaka leo, tekanyo e tlase ea tekanyo ea mafura (sc, 0.03 mg / kg) e thibetsoe 'ho lebella' chow hypophagia.

Nalmefene e boetse e fapane ka tsela e fapaneng ea phepo e tsoang ho ea fepa ka bobeli ho ea ka histori ea lijo (ho ja lipale × dose: F (5,65) = 6.60, p<0.001; lethal dose: F (5,65) = 6.28, p<0.001). Ka ho khetheha, nalmefene ka matla (ED₅₀= 0.025 mg / kg, r²= 0.97) le ho fokotsa ho kenngoa ha lijo tse khethiloeng ka likhofu tse khethiloeng tse khethiloeng ka mokhoa o nepahetseng, F (1,30) = 35.37, p<0.0001), ntle le phetoho e ts'epahalang ea ho ja likhoto tsa chow / chow tse fepehileng (Setšoantšo sa 3, bohareng).

Tumellanong le liphuputso tsena, phekolo e nepahetseng e boetse e fokolitse ka ho fapana palo e fokolang ea metsotso ea 20 ea lihlopha tse peli, e bontšitsoeng ka kakaretso (F (5,65) = 5.31, p<0.0001) le phapang e fapaneng ea log (F (1,13) = 44.68, p<0.0001) nalane ea lijo × litlamorao tsa tšebelisano ea lethal dose. Nalmefene e fokotsa ka mokhoa o atlehileng ho ja likhoto tsa chow / tse khethiloeng le tsa chow / chow (log-linear: letsoapong: -4.05 ± 0.94 vs -0.69 ± 0.32 kcal / dose increment, ka ho latellana). Nalmefene e boetse e fokolitse ka ho fokotsa palo ea 20 ea metsotso e ntseng e kenngoa ka khetho / ho rata likhoto (tekanyo: F (5,35) = 8.48, p<0.0001), ho fokotsa ho ja haholo ho 0.1, 0.3, le 1 mg / kg tekanyetso, athe ke tekanyetso e phahameng feela (1 mg / kg) e neng e sebetsa ho likhoto tsa chow / chow (dose: F (5,30) = 2.70, p<0.05). Ka kakaretso, lethalofo ea nalmefene e phahameng ka ho fetisisa (1 mg / kg) e fokolitse kakaretso ea metsotso e 20 ea ho ja likhoto tsa chow / tse fepehileng ho isa boemong bo seng bo sa fete ka ts'epahalo ea taolo ea kalafo ea chow / chow-fed (Setšoantšo sa 3, ho le letona). Kalafo ea Nalmefene e ne e sa bontše liphello tsa carryover ka ho qeta lijo tsa pele kapa tsa bobeli ha ho kenngoa lijo ka mor'a matsatsi a kalafo.

Hypothesis 4:

Li-rats tse nang le li-intermittent, tse fokolang haholo ho fihlella lijo tse tsoekere, li tla ja haholo.

Ho rua 'mele le katleho ea phepo

Li-rats / likarolo tse khethiloeng li fumane boima ba 'mele ho feta likhoto tse fepehileng / tse fepehileng (histori ea lijo: F (1,13) = 10.79, p<0.01; nalane ea lijo × letsatsi: F (14,182) = 5.96, p<0.001). Liphapang tse kholo tsa sehlopha li ne li bonahala ka letsatsi 5 (matsatsi a 4 pele ho phapang ea tšebeliso ea matla a bokelloang), e eketseha ho fihlela ka letsatsi la 15 (Setšoantšo sa 4a). Motšehare 15, litoeba tse nang le khethollo / tse fetiloeng li ne li fumane 14.3 g ho feta likhoho tse fepehileng / tse fepehileng ho sa tsotellehe ho noa 92 kcal feela le ho fumana 2.5 feela ho fihlela lijo tsa tsoekere. Ts'enyehelo ena ea boima ho feta matla a ho kenngoa ha matla a bona a bonahatsa keketseho ea ho atleha ho fepa lijo (Setšoantšo sa 4b), e neng e fapane haholo ka histori ea lijo (F (1,12) = 10.14, p<0.01) ka letsatsi 5. Ka letsatsi la 24, likhoto tsa chow / tse fepehileng tse ratoang li ne li le boima bo felletseng ho feta likhoto tsa chow / chow tse fepehileng (Setšoantšo sa 5a), 'me ba ne ba le 11% boima haholo ka letsatsi 53 (ho sa tsotellehe hore ba fumane feela ~ 9 h kakaretso ea ho fumana lijo tse khethiloeng).

Boemo le boemo ba endocrine

Boima bo feteletseng ba 'mele e ne e le ka lebaka la keketseho ea 57% ea mafura a mafura (Setšoantšo sa 5b, ho le letšehali). Ka lebaka leo, likhofu tse fepehileng / tse fepehileng li ne li le mafura, joalokaha ho hlalosoa ke keketseho e khōlō ea mafura a 'mele, ho se na phetoho karolong ea boima ba' mele e entsoeng ke FFDM (Setšoantšo sa 5b, ka ho le letšehali) le ho fokotsa metsi% (e bolelang ± SEM: 71.9 ± 0.8 vs 74.3 ± 0.7%, p<0.05). Tlhatlhobo ea mafura e bontšitse keketseho e kholo ea li-subcutaneous (inguinal; keketseho ea 41%) mme haholoholo visceral (gonadal; 76% keketseho) depo tsa mafuraSetšoantšo sa 5, ho le letona).

Plasma, likarolo tse khethiloeng tse khethiloeng ke 60% li phahameng leptin-immunoreactivity, 47% e tlaase GH-immunoreactivity, le 59% e tlaase e nang le ghrelin-immunoreactivity, ha e bapisoa le likhoto tse fepehileng /Setšoantšo sa 6a-c). Joalokaha ho ne ho lebeletsoe, plasma leptin-immunoreactivity e amana haholo le boima ba mafura ka hare ho (rs = 0.82 le 0.86 bakeng sa lihlopha tsa khefu / tse khethiloeng le tse khethiloeng, ps <0.05) le ho pholletsa le lihlopha (r= 0.91, p<0.001) (Setšoantšo sa 6d) hammoho le ka gonadal (r= 0.85, p<0.001) le masisa a mafura a inguinal (r= 0.78, p

TŠOHLOA

Lipoe tse tšehali tse nang le mokhoa o boima oa ho ja lijo tse ngata haholo, li ja lijo tse nang le phihlelo-li itšetlehile ka ho ba le phihlelo ea ho ja le ho nahana ka tsela e sa tloaelehang. Liphetoho tse amanang le boitšoaro ba ho fepa e ne e le li-dissociable ho tloha ka nako e itseng, ho batho ka bomong, le ka tekanyo ea bona ea phepelo ea pharmacological-karabo ho mohanyetsi oa li-opioid-receptor, ho fana ka maikutlo a hore ba emela mekhoa e fapaneng e fokolang-e susumelletsoeng ke li-etiologies. Li-rats tse nang le mokhoa o fokolang oa ho fihlela lijo tse ratoang haholo li boetse li bontšitse ho eketseha ho tšoenyeha ho tšoenyehileng 'me ka potlako e ile ea e-ba matla haholo.

Ho ja lijo-thollo joaloka ho ja ho ile ha hlaha ka potlako (EC₅₀= Matsatsi a 3.2) ka ts'ebetso ea ho hōla ha lintho, e lumellanang le ho tloaela ho ithuta, ho kopanya lihlopha (Hartz et al a, 2001). 'Binges' e ne e le ea bohlokoa, e leng karolo ea halofo ea caloric ea letsatsi le leng le le leng 'me e ne e le ~ 7 e kholo ho feta caloric ho noa e neng e khona ho boloka likhoka-laola-bolokolohi likhoka tse pepenene nako e khutšoanyane (2 h) nako. Nakong ea matsatsi a pele a 8 ea teko (ha ts'ebetso ea hypophagia e ne e e-s'o ntlafatsoe), 'li-binges' li etsahetse le hoja litoeba li ne li sa tsoa ja lijo tse ling tse sa ntseng li e-na le lihlahisoa tse ngata tse tsoang ho ea fepa pele. Matsatsing a latelang, tekanyo ea tebello ea tebello ea hypophagia ha e e-s'o fihlele tekanyo ea ho ja lijo tse ngata. 'Binges' e ne e fokotsoa ka tekanyo ea tekanyo ea li-dose ka tekanyo e fokolang haholo ea li-nalmefene (ho ea ka tse atisang ho sebelisoa libukeng), khethollo μ/κ mohanyetsi oa li-opioid-receptor o kopanyang ho noa joala ethanol ka joala (Mason et al a, 1994, 1999) le e fokotsang ho sebelisoa le ho iketsetsa 'monate' oa lijo tse monate ho batho (Li-yoom et al a, 1990; Li-geom le Grey, 2002; Yeomans le Wright, 1991). Li-rats li ile tsa ja ka potlako ka har'a li-binges (~ 2.9 s / 45 mg pellet ntle le ho fokotsa nako e sa jeng), ka potlako ho feta litoeba tse bolokiloeng ad libitum lijong tse tšoanang tse khethiloeng (litemoso tse sa hatisoang). Liphuputso ka kakaretso li fana ka maikutlo a hore karolo ea hedonic ho liphetoho tse kang ho itlopa joala. Ho khahlisang ke hore tšekamelo ea ho hlahisa lijo tse kang ho itlopa joala e ne e le tšobotsi e tsitsitseng, e ikhethileng ea motho ka mong, e nang le boitsebiso bo ikarabellang bakeng sa 79.7% ea phapang ea boholo bo tloaelehileng ba likarolo tsa 'ho itlopa joala'.

Le hoja ho ja lijo-thollo tse kang ho ja lijo tse hlahisitsoeng ka mokhoa o thibelitsoeng, ho ja lijo tse khethiloeng, litlhapi tse fetiloeng ke khethollo li ile tsa fokotsa ho ja lijo tse sa khethiloeng malapeng a tsona le ka ho ba le pele ho nako le postdeprivation (likarolo tsa pele) . Ho qala ha li-hypophagia tsena ho fapane, ka ho ts'oanela ho ts'oaroa ka matlong a ntlo (letsatsi la 3) pele ho tse fanang ka lijo tsa pele (letsatsi la 9) le linako tsa tlhahlobo tsa pele ho letsatsi (11) ka nako ea libeke tsa 1. Lithuto li ne li sa reretsoe ho khetholla mekhoa e ikarabellang bakeng sa ho fokotsa matlo a lehae kapa ho ja lijo tsa predeprivation. Leha ho le joalo, liphuputso tse 'maloa li tšehetsa tlhaloso ea hore chow hypophagia ea ho fepa ka lekhetlo la pele e ne e le mokhoa oa ho lebella phapang e mpe (Flaherty le Checke, 1982; Flaherty le Rowan, 1986; Flaherty et al a, 1995) mme eseng matla a matšeliso a homeostatic bakeng sa ho fumana boima bo boima, satiety e sa feleng, kapa phapang e fapaneng e latellanang. Ntlha ea pele, ho ne ho se na kamano e fapaneng kapa e neng e le teng pakeng tsa phapang pakeng tsa boima ba 'mele le boholo ba chow hypophagia (ho fapana le liphapang tse matla tse bonoang ka chow hypophagia). Ntlha ea bobeli, pele ho ts'ebetso ea ho fokotsa lijo e qalile matsatsi a 2 pejana 'me e ne e le kholo ho feta hypophagia nakong ea pele ho nako ea pele. Tlhaloso ea homeostatic ea matla e ne e tla bolela esale pele le boholo bo ts'oanang (haeba e sa lebelo kapele le boholo bo boholo ba anorexia nakong ea pele ho nako ea pele ho ts'ebetso), haeba hypophagia e lekanngoa e ne e tšehetsoa ka mokhoa o hlakileng ka ho fana ka lipuo pele. Ntlha ea boraro, ho ne ho se na ho se lumellane ho fapaneng pakeng tsa tekanyo ea pele ea phepo ea hypophagia le boholo ba likhaoana tsa bobeli tsa ho fepa. Ntlha ea bone, pele ea ho fepa hypophagia (EC₅₀= Matsatsi a 7.5) a hlahisitsoe ~ matsatsi a 4-5 ka mor'a ho ja lijo tse kang ho ja. Tumellanong le liphello tsa hona joale, phapang e lebelloang e sa lebelloang bakeng sa tharollo e ntle e amohelehang e hlaha ntle le boima ba 'mele kapa liphetoho tsa caloric, ha tharollo ea histori e atleha ka tharollo e eketsehileng ea saccharin (Flaherty le Rowan, 1986). Leha ho le joalo, mokhoa o ka khonehang oa ho sebelisa matla a homeostatic matla a ho fetola moputso oa ho amoheloa ha lijo lenaneong la hona joale o ke ke oa khelosoa. Ka mohlala, litekanyetso tsa leptin le ghrelin, li-hormone tse laoloang ke takatso ea lijo tse laolang moputso oa li-neurocircuitry (Hommel et al a, 2006; Abizaid et al a, 2006; Hao et al a, 2006; Shizgal et al a, 2001) e fapane ka lebaka la histori ea lijo 'me mohlomong e fetotsoe pele ho e-ba le phapang ea' mele ea pele. Tlhahlobo ea nako e telele ea leptin le ghrelin kapa maemo a phekolo ea meriana ea liketso tsa bona e ka thusa ho hlakisa monehelo leha e le ofe oa matla ana a matla a homeostatic a ho laola ho ea ka tebello ea ho ithuta hypophagia lenaneong lena la hona joale.

Joalo tabeng ea ho itlopa joala, litsuoa ka bomong li boetse li fapane ka mokhoa o fapaneng ka tekanyo eo li hlahisitseng ho lebella phapang e fosahetseng ka eona, ka likarabo tsa boitsebiso bakeng sa 74.3% ea phapang pakeng tsa lijo tsa pele. Leha ho le joalo, bohlokoa haholo, leha ho le joalo, tšobotsi ena e ne e sa tsamaisane le ea morao-rao ho feta ho ja lijo tse kang binge. Hape, ha ho na le lisebelisuoa tse nang le lisebelisoa tse fapaneng le tsa monophasically tse fokotsoang ho itlopa lijo-joaloka ho ja le ED₅₀ ea 0.025 mg / kg le haufi le ho tloaeleha ha lijo tsa phepo ea 1 mg / kg, mohanyetsi oa li-opioid o thibelitse ho lebella phapang pakeng tsa sekhahla se le seng feela (0.03 mg / kg).

Tlhokomelo ea tlhaho ea hypophagia ea ho qala ho fepa e ntlafalitsoe ka lebaka la ho eketseha ha lipolelo, ho lumellana le mokhoa oa ho ithuta, oa ho kopanya (Hartz et al a, 2001). Bopaki bona ba ho tloaelana, ho ithuta ho fetoha ha bo lumellane le mekhoa e mengata ea litsela tse ling, ho kenyelletsa hore ho ne ho se na maemo a mangata ho feta nako, hore thuto e ne e sa kopane le tlhaho (mohlala, ho hlohlelletsa kapa ho tloaela ho ja lijo kapa mekhoa ea teko) kapa tse ngata tse sa ithutoang litloaelelo (mohlala, fetola ka boholo ba mpa, phetoho e seng ea Pavlovia ka matla a matla a hormone a homeostatic). Likhopolo tse 'maloa li ka' na tsa sebetsa e le boitsebiso bo tsitsitseng ba ho fumaneha ha lijo lijo tse atamelang, ho kenyeletsa le experimenter, tikoloho ea tlhahlobo, nako ea ho hanela, esita le sehlahiswa sa pele sa lijo (chow). Ha e le hantle, hyperphagia e ne e fokotsoe haholo (10.9 kcal, kapa 34%, tlaase, p<0.001) haeba phepelo ea pele e ne e sa hlahisoe, e tsamaellanang le karolo e fumanoeng bakeng sa tšusumetso ena ho hlophiseng kapa ho nolofalletsa ho ja lijo tse ratoang (data e sa bontšitsoeng). Ho sebetsana le litšitiso tse joalo ho tla ba molemo ho khetholla lipakeng tsa likarolo tse se nang maemo le maemo a khethiloeng a lijo tsa hyperphagia le likaroloana tsa methapo ea kutlo.

Ho joalo, a μ/κ mohanyetsi oa li-opioid-receptor, ho fokotsoa ka tsela e fapaneng ea ho itlosa bolutu ka lijo tsa hyperphagia ho lumellana le litlaleho tsa nakong e fetileng ea hore tsamaiso ea opioid e sa feleng e boloka taolo ea hedonic, ho e-na le phepo e nepahetseng, ho kenya letsoho ho batho le liphoofolong (Olszewski le Levine, 2007). Liphuputso tse 'maloa tse fetileng li tšehetsa khopolo ea hore li-receptor tse nang le li-opioid tse nyenyane li etsa hore likarabo tsa boitšoaro li be le likarabo tse khotsofatsang, ho kenyelletsoa ho sebelisoa ha lijo tse khethiloeng ka makhetlo a mangata (Kelley et al a, 2002). Nalmefene e ka 'na ea e-ba le mokhoa o fokolang oa ho ja ka ho thibela li-receptor tsa opioid sebakeng sa ventral tegmental, ka hona ho thibela li-interneurons tsa GABAergic tse thibelang likokoana-hloko tse lumellanang le dopamine neurons le ho fokotseha ha dopamine sekhethong sa nucleus accumbens (Taber et al a, 1998; MacDonald et al a, 2003, 2004). Nalmefene e ka 'na eaba o ile a nka bohato ka ho thibela μ-opioid receptors nucleus accumbens shell kapa ventral pallidum (Woolley et al a, 2006; Ward et al a, 2006), likaroloana tsa tšebelisano ea methapo ea kokoana-hloko bakeng sa ho matlafatsa litakatso tsa lijo tse khethollang, lintho tse sebelisoang hampe, le meputso e meng (Smith le Berridge, 2007; Kelley et al a, 2005).

Phapang e fapaneng e sa lebelloang e 'nile ea hlalosoa ka tsela e fapaneng le e kang: tekanyetso (eo bohlokoa ba hedonic ea boleng ba pele bo fokotsehang ka lebaka la litšoantšiso tsa histori kapa tsa ho bapisa ho monate haholoanyane), ho thibela (moo litoeba li ithutang hore monate o khethiloeng haholo o atametse le ka tsela e lumellanang ho thibela ho ja ka mokhoa o sa rateheng, oa ho ipolaea, o motle), kapa oa tlhōlisano ea boitšoaro (moo ho behoang boikutlo bo lebeletsoeng ho sitisa ho kenngoa ha lijo pele) (Flaherty et al a, 1995). Le hoja boitsebiso ba hona joale bo sa khetholle ka ho hlaka pakeng tsa litlhaloso tsena, li fana ka maikutlo a tlaleho ea hedonic, e seng ea matla ea homeostatic ea ho lebella phapang e fosahetseng. Ntlha ea pele, ho na le tebello ea ho ipolaea e ileng ea e-ba teng ho sa tsotellehe 2 e fetileng ea lijo tse hlokang lijo, ka mor'a moo e ka 'nang ea lebella hore liphoofolo li amohele lijo tse nang le matla. Tlhaloso ena e lumellana le ho hlokomoloha hore lijo tse lahleheloang ke lijo li eketsa kutloisiso ea bothata (Hunt et al a, 1988; Kauffman et al a, 1995).

Ntlha ea bobeli, tekanyo e le 'ngoe e tlaase ea nalmefene (0.03 mg / kg) e thibelitse ho lebella ho ts'oana le phetoho, ha ho ntse ho fokotseha monophasia ho ja lijo tsa likhoho tse e-s'o ka tsa e-ja lijo tse khethiloeng. Liketso tsa ho khetholla ha li-chow li ja ka ho tšehetsa tšehetso ea histori ea phepo ea maikutlo ea hore li-opioids li boetse li kenya letsoho ho motsoalle ea ithutang, mekhoa e khotsofatsang e tlatsetsang ho amoheloa le ho khethoa lijo (Barbano le Cador, 2006; Jarosz et al a, 2006; mesifa et al a, 2004). Sephetho sena se fapane le maikutlo a atileng ao bahanyetsi ba li-opioid-receptor ba nang le eona feela ke anorectic ka bobeli (haholo-holo bakeng sa lijo tse monate) kapa mokhoa o tloaelehileng oa ho hlahisa lijo tse hlahisang 'intrinsic' hedonic (Cooper, 2004; de Zwaan le Mitchell, 1992).

Likhoto tse fumaneng phihlello e fokolang haholo ho tsoekere, lijo tse ratoang haholo ka boithatelo li bontšitse boits'oaro bo ts'oanang le ho tšoenyeha letsatsi le le leng kamora ho fihlella ha bona haufinyane lijong tse ratoang. Boholo ba rat ea ho itlopa joala bo ne bo amana haholo le boits'oaro bo latelang ba boits'oaro. Hore na boits'oaro bo ts'oanang le khatello ea maikutlo bo bakiloe ke nalane ea nako e telele ea lijo kapa ho tlohela ka matla (Cooper, 2004) ho ja lijo tse khethiloeng ha li hlake hantle. Ho fihleloa ha lijo lijo ka bobeli 'me ha ho bonolo hore li-hypophagia tsa morao-rao li ikarabelle ka ho eketseha ha matšoenyeho-joaloka boitšoaro hobane ho hlophisoa ha lijo ho hlophisitsoe ho eketsehileng ho hlahloba matsoho a bulehileng ho feta-maze, e leng phello e tšoanang le ea anxiolytic (Inoue et al a, 2004). Ka tsela e ts'oanang, ho ba botenya ha ho bonolo ho ikarabella ka ho eketseha ho tšoenyeha-joalo ka boitšoaro hobane lintja tse khotsofatsang le tse ngata haholo ha li fapane le boitšoaro ba metso-bohloko (Chaouloff, 1994) 'me kahobane ho khethoa lijo tse nang le phepo e ngata haholo le tse bakoang ke lijo tse bakoang ke lijo, ha li itšetlehe feela ka maikutlo a fapaneng tšimong (Levin et al a, 2000). Potso ea bohlokoa bakeng sa thuto ea nakong e tlang ke hore na boitšoaro bo kang ba matšoenyeho bo bontšoang ke likhoho tse khethiloeng ke khefu / khethollo li tsoa ho fumana lijo tse khethiloeng ka bobeli, ho fapana le mokhoa o fokolang haholo oa ho fihlella. Leha ho le joalo, liphello li bontša hore likhoho tse nang le phihlelo e feteletseng ea lijo tse khethiloeng li ne li sa bontše feela ho ja lijo, empa hape li tšoenyehile haholo ka boitšoaro, ho fumanoa ho fapana le ho tšoenyeha ha mathata a ho ja joala le botenya ka lehlakoreng le leng ho tse ling (Gluck, 2006; Kessler et al a, 1994; Specker et al a, 1994).

Likokoana tse fokolang ho ja lijo tse khethiloeng li fumane boima ba 'mele le mafura a sa amaneng le matla a mangata a sebelisoang, liphihlelo tse ke keng tsa baloa ka nako eohle ea phihlelo eo ba e filoeng ho lijo tse khethiloeng (~ 9 h). Lijo li ne li e-na le mafura, liprotheine le lik'habohaedreite tse tšoanang, ka hona ho se tšoane ha lihlopha tsa macronutrient ha ho hlalose liphello. Ho sa tsotellehe ho ja 8.3% matla a mangata, likhoto tse fokolang ho fumana lijo tse khethiloeng li fumane 71.3% boima ba 'mele bo fetang matsatsi a 15. Qetellong ea thuto, litoe tse khethiloeng ke khetho / khethollo li ne li fumane 88% boima ba 'mele bo eketsehileng, ka lebaka la ho eketsoa ha mafura a' mele, ho eketsang kotsi ea lefu la pelo le mafu a metabolism (Hantle, 1993; Wajchenberg, 2000). Ntho e matlafatsang ea ho ja lijo tsa likhoho tse ratoang haholo li ka bakoa ke li-sucrose tse nang le lijo tse khethiloeng (Kanarek et al a, 1987; Kanarek and Orthen-Gambill, 1982) hammoho le tloaelo e fumanoeng ea ho ja meroalo e matla ea matla ka mor'a linako tsa boithati tsa hypophagia (Batista et al a, 1997). Mokhoa ona oa ho iphelisa oa 'lijo-o fepehileng' oa phepo e tsitsitseng ea lijo o sitisitsoe esale pele ka mokhoa o le mong oa lijo / li-binge tse kholo tse jang mefuta ea dieters e meng le bakuli ba nang le mathata a ho ja le, ka likarabo tse kholo tsa insulin (Calderon et al a, 2004; Taylor et al a, 1999), e ka khothalletsa lipogenesis.

Li-rats tse fumanoang li fokolloa haholo ho fumana lijo tse khethiloeng li bile li fetohile liphetoho tsa endocrine tse bonoang ke botenya ba batho, ho kenyeletsa le ho eketseha ha leptin (Nahana et al a, 1996) mme o fokotseha ho potoloha Ser³-n-octanoylated ghrelin maemo. Leptin, ea ob sehlahisoa sa liphatsa tsa lefutso, ke 16-kDa, haholo-holo tšoeu e hlahisoang ke li-hormone tse tsamaeang tse tšoeu (adipose)Bates le Myers, 2003; Guha et al a, 2003; Pico et al a, 2003) e sebetsang e le letšoao le fanang ka maikutlo a fosahetseng ho laola matla a tekanyo ea matla. Ka li-store tse ngata tse ntseng li eketseha, ho potoloha litekanyetso tsa leptin ho eketsa ho thibela takatso ea lijo le ho sebelisa matla a ho sebelisa matla (Bates le Myers, 2003). Ka hona, thuputsong ea hona joale, litekanyetso tsa leptin li eketsehile 'me li kopantsoe ka matla le boima ba mafura a mangata (Nahana et al a, 1996; Maffei et al a, 1995). Ho fapana le leptin, ghrelin, ligname ea 28, e setseng ka mor'a phetolelo e fetoletsoeng ka morao-phetolelo, e sebelisoang ka mor'a hore e amohelehe ka GHSR1a, e na le hormone e ngata e tsoang ka mpeng, e nang le anabolic e eketsehileng ka matla a se nang matla a ho bonts'a tsamaiso ea methapo ea methapo . E fuoa pharmacologically, Ser³-nmofuta o motsoako oa ghrelin ke orexigenic mme o fokotsa matla a ho sebelisoa ha matla le tšebeliso ea mafura e le matla a tsamaiso ea matla a matla, e lebisang boemong bo boima le bofokoli bo nang le bolaoli bo sa feleng (Nakoana et al a, 2006; Tschop et al a, 2000; Wortley et al a, 2005). Hobane leptin le ghrelin ka ho latellana li eketsehile 'me li fokotsehile linthong tse nang le khefu / khethollo, ho nona haholo le ho fokotsa lijo ho ka' na ha hlahisoa ho sa tsotellehe matla a ho leka-lekaneng, ho lula malapeng ho ea ho boima ba lihomone tse peli (ho tšoana le ho ja botenya ba motho) lokolloa.

Botenya ba motho bo 'nile ba amahanngoa le ho fokotseha ha likhahla tsa serum GH, tse bontšang ho fokotseha halofo ea bophelo, palo ea liketsahalo tsa sekhukhu, le tlhahiso ea letsatsi le letsatsi (E fokotseha et al a, 1999). Likarolo tse khethiloeng ke Chow / tse fepehileng li ile tsa bontša le ho fokotsa 47% ho potoloha GH. Ho latela mokhoa o ka 'nang oa e-ba le pathophysiologic, maemo a fokotsehang ka likhahla tsa GH (mohlala, botsofali, lefu la GH le ho ba motenya haholo) le kotsi ea lefu la pelo (Gola et al a, 2005; Hoffman, 2005).

Ka kakaretso, likhoto tse nang le mokhoa o fokolang oa ho fumana lijo tse phahameng haholo, lijong tse ratoang haholo li entsoe ka mokhoa oa ho ja le ho lebella phapang e sa thabiseng, e leng ntho e ka khonehang ea ho amoheloa ke lijo, ho liphoofolo tsa basali tsa Wistar. Bana ba ithutileng, ho ba le bothata-ba susumelletsehang ho fokotsa lijo ba ne ba itšetlehile ka li-opioid 'me ba ikarola ka nako le batho ba bang. Palo e le 'ngoe e tlaase ea sekhahla se sireletsehileng se thibile ho lebella phapang e fosahetseng' me e fokotseha butle-butle 'me e fokotseha butle-butle' ho itlopa lijo, 'hoo e ka bang tlhahiso ea caloric e tloaelehileng. Li-rats tse fokolang ho fumana lijo tse tsoelang pele tsa sugary li bontšitse ho eketseha ho tšoenyeha joaloka boitšoaro le matšoao a morphometric le li-hormonal tsa botenya ba mafura a visceral. Liphello li tšehetsa khopolo ea hore lijo tse thibetsoeng haholo li ka 'na tsa e-ba le karolo ea ho ntlafatsa ho ja lijo tse ngata, lijo tsa lijo, botenya le mathata a amanang le eona.

Notes

Tlhaloso / likhohlano tsa thahasello

Bangoli ba phatlalatsa hore ha ho lintoa tse thahasellisang.

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