Opioid-Akuyembekezeratu Chiyembekezero Chosiyanitsa Cholakwika ndi Kudya Kwambiri Monga Kudya M'zakumwa Zoperewera Kwambiri ku Chakudya Chofunika Kwambiri (2007)

Keywords:

kudya zakudya zolimbitsa thupi, kuyerekezera zosiyana, kusiyana kochepa, chakudya chopatsa thanzi OR kudya, kunenepa kwambiri kwina kapena kunenepa kwambiri, kunenepa, kuwonetsetsa kwa hedonic, kuchepa, μ opioid-receptor kapena κ wotsutsana ndi opioid-receptor, bulimia OR bulimic, vuto la kudya, nkhawa, ghrelin, leptin, hormone ya kukula, makoswe aakazi

Pamwamba pa tsamba 

MAU OYAMBA

Kudya kudya ndi khalidwe losazolowereka lodyetsa lomwe limakhala ndi nthawi yofulumira komanso yowonjezera. Zomwe zimayambitsa matenda, zomwe zimayambitsa matenda osiyanasiyana, zimakhala ndi zakudya zokoma kwambiri shuga ndi mafuta komanso 'kutaya mphamvu' (Association of Psychiatric Association, 2000; Corwin ndi Buda-Levin, 2004; Yanovski, 2003). Kudya kwambiri kumakhala kofala kwambiri kwa anthu odzaza kwambiri ndipo, mofananamo, odyera mowa nthawi zambiri amawopsa kwambiri (Pike Et al, 2001; Smith Et al, 1998). Choncho, kudya mowa mwauchidakwa ndi chiopsezo chotengera kulemera kwa thupi (Hudson Et al, 2007). Kusokonezeka kwakukulu pakati pa kudya zakudya ndi dysphoria kwawonetsedwa ndipo chikhalidwe cha chikhalidwe ichi sichingakhale chosatsimikizika (Blazer Et al, 1994; Gluck, 2006).

Zochitika zamakono zolimbitsa thupi zimagogomezera ntchito yothetsera zakudya m'kulimbikitsa kulimbitsa thupi (Howard ndi Porzelius, 1999), ndi zinyama zambiri zomwe zikuwonetsa kuti mbiri ya zakudya zowonongeka, zomwe zimawonetseratu kuchepa kwa tsiku la caloric ration (mwachitsanzo 66% ya kudya tsiku ndi tsiku) (Hagan Et al, 2003) kapena nthawi ya chakudya cha tsiku ndi tsiku (mwachitsanzo 2 h) (Inoue Et al, 2004), ndizofunika kwambiri kuti munthu adye. Komabe, njira ina yodzisankhira bwino ingagogomeze mkhalidwe wokhudzana ndi zakudya, zomwe zimayesedwa kuti azipewa kudya zakudya zolimbitsa thupi, "zakudya zoletsedwa,Kales, 1990; Knight ndi Boland, 1989; Fletcher Et al, 2007; Mitchell ndi Brunstrom, 2005; Gonzalez ndi Vitousek, 2004; Kusakanikirana ndi Amatsenga 2004; Corwin, 2006; Corwin ndi Buda-Levin, 2004). Odyera zakudya amangofuna kudya zakudya zoletsedwa kuti "kudya" kumangokhala kochepa chabe, nthawi zambiri kumakhala kovuta, nthawi zina zimakhala zovuta, mwina zowonongeka ndi mphamvu zochepa.

Zotsatira za zakudya zoletsedwa, zomwe zimayembekezeredwa ndi chakudya chokoma, zimayambitsa kukana njira zina zovomerezeka kwa anthu.Pliner Et al, 1990). Kusintha kotereku pakuvomerezeka kwa chakudya kungawonjezere chiopsezo cha kuchepa kwa thupi ndi matenda odwala chifukwa cha kuchuluka kwa ntchito yomwe imayikidwa pa-hedonic, m'malo mwa zakudya, katundu wa chakudya choletsa kudya (Wardle Et al, 2001). Mwina analog ya ophunzira awa amasintha pakuyanjidwa kwa chakudya, kusiyana kosiyana mu makoswe kumatanthawuza kuti hypophagia ndi yovomerezeka mosiyana kwambiri chifukwa chokhala ndi mwayi wololedwa kwa chinthu chofunika kwambiri nthawi yomweyo musanayambe (kutsutsana mosiyana) kapena kusiyana) chinthucho (Flaherty ndi Checke, 1982; Flaherty ndi Rowan, 1986; Flaherty Et al, 1995). Zotsatira zakusiyanitsa zidaphunziridwa kale pogwiritsa ntchito zochepa (3-5 min) mayankho okoma m'miyeso yolemetsa, koma sanaphunzirebe bwino kuvomereza / kudya chakudya chamasiku ndi tsiku m'maphunziro- kudziwa kulemera kwa thupi.

Choncho, kudya ndi kukana zosakondera, koma mwinamwake wathanzi, zakudya zikhoza kuimira kusintha kwa machitidwe osiyana-siyana omwe amamva bwino ndi zakudya nthawi yambiri. Poyamba, zozizwitsa izi zasankhidwa kuzinthu zosiyana siyana za kuphunzira ndipo sizinaganizidwe chifukwa chogwirizana nawo. Phunziroli linayesa kuyesa malingaliro akuti makoswe okhala ndi chakudya chochepa chokhala ndi chakudya chofunikanso amatha kukhala ndi zakudya monga zakudya zamakono ndi zosiyana zosiyana, kapena hypophagia, zomwe sizivomerezedwa, chakudya choyambirira. Motero, cholinga chachikulu cha phunziroli chinali kuyesa kuganiza kuti kudya mowa kwambiri ndi kuyembekezera zosiyana ndi zosiyana ndizomwe zimagwirizanitsidwa ndi mizu ya etiologic, monga momwe zikuwonetseratu zotsatira zowonjezera chakudya chokoma.

Cholinga chachiwiri cha phunziroli chinali kuyesa malingaliro akuti apadera μ/κ opioid-receptor antagonist nalmefene angachepetse osati kudya kokha monga chakudya chofunika kwambiri, komanso amasiyanitsa kudya chakudya chosafunika kwambiri malinga ndi mbiri ya zakudya. Nalmefene adaneneratu kuti azidzadya zakudya zosiyana ndi zosiyana siyana, kuchepetsa chakudya chowongolera m'nkhani zomwe sizinasangalatse zakudya zakusakaniza, koma kuwonjezeka kwa zakudya zochepa zomwe zimakonda kwambiri chakudya. Bukuli, kufotokoza kwachiwiri kumachokera pa zomwe apeza (1) monga kudya ndi kuyembekezera zosiyana zosiyana zimakhala zofanana ndi zomwe zimayambitsa kudya (Corwin, 2006; Flaherty Et al, 1995) ndi kuti (2) otsutsa opioid-receptor antagonist amalephera kugwirizanitsa (Cooper, 2004; Amatsenga ndi Oyera, 2002).

Gawo lachitatu la zolinga zofotokozera ndikutanthauzira khalidwe lokhudzidwa ndi nkhawa ndi zotsatira zokhudzana ndi kusokonezeka kwa zakudya zochepa, zochepa kwambiri zowonjezera zakudya zowonjezera, zomwe zili pansi pano. Kuti mudziwe ngati makoswe omwe amalandira kuchepa kwa chakudya chofunikika adakula kwambiri-monga khalidwe, nkhanizo zinayesedwa pazowonjezereka. Kuti mudziwe ngati makoswe okhala ndi zakudya zoterezi amatha kukhala ochepa kwambiri, kusintha kwa chakudya choyenera, kulemera kwa thupi, kuchepa, ndi kuyendetsa leptin, 'yogwira' ghrelin, ndi kuchuluka kwa mahomoni olemera (GH).

Pamwamba pa tsamba 

ZIDA NDI NJIRA

Ophunzira

Wachinyamata wachinyamata Wistar amadwala (n= 23 126-150 g, masiku 41-47; Mtsinje wa Charles, Raleigh, NC) anali osakwatiwa-omwe ankaloledwa kufika pakhoma, mapepala apulasitiki (19 × 10.5 × 8 masentimita) mu 12: 12 h lita (kutsogolo kwina, 0800 amazimitsa), chinyezi- (60% ), komanso kuyendetsa kutentha (22 ° C) vivarium. Mphuka inali ndi digito yokhala ndi chimanga (Harlan-Teklad LM-485 zakudya 7012: 65% (kcal) makapu, 13% mafuta, 21% mapuloteni, 3.41 kcal / g; Harlan, Indianapolis, IN) ndi madzi ad libitum kwa sabata la 1 zisanayambe kuyesedwa. Ndondomeko zogwiritsidwa ntchito ku National Institutes of Health Guide kwa Care and Use of Laboratory Animals (NIH Publication nambala 85-23, yowonongeka 1996) ndi 'Malamulo a zoweta zinyama' (http://www.nap.edu/readingroom/bookslabrats) ndipo adavomerezedwa ndi Institute Institutional Animal Care and Use of The Scripps Research Institute.

mankhwala

Nalmefene hydrochloride, kapena 17- (cyclopropylmethyl) -4,5α-popoxy-6-methylenemorphinan-3, 14-diol hydrochloride (Mallinckrodt, St Louis, MO) idasungunuka mwatsopano mu saline ya isotonic. Nalmefene amamangirira mwamphamvu κ (K_i= 0.083 nM) ndi μ (K_i= 0.24 nM) opioid receptor subtypes, koma ~ 2 amalamulira mofulumira kuti δ, kusiyana ndi μ or κ, receptors (K_i= 16.1 nM). Momwemonso, nthende ili ndi mdani wamkulu wotsutsa κ ndi μ (KODI₅₀= 18.5 ndi 13 nM, motsatira), koma osachepera δ, subtypes (Bart Et al, 2005; Culpepper-Morgan Et al, 1995; Emmerson Et al, 1994; Michel Et al, 1985).

Kukonda Zakudya

Pofuna kudziwa zakudya zamtundu wina, makoswe (n= 8) adapatsidwa chakudya chokwanira komanso chakudya chokwanira chokwanira, chokoleti chokwanira, chosekemera chapamwamba (50% kcal), zakudya za AIN-76A zofanana ndi zomwe zimagwiritsidwa ntchito mofanana ndi zowonongeka komanso mphamvu yowonjezera (chokoleti-flavored Fomu ya PJPPP: 69.1% (kcal) makapu, 11.8% mafuta, 19.1% mapuloteni, metabolizable mphamvu 3.70 kcal / g; anapangidwa ngati 45-mg yolondola zakudya pellets kuwonjezera kukonda kwake, Cooper ndi Francis, 1979; Zofufuzira Zofufuza Inc., New Brunswick, NJ) (onani Gulu 1). Pambuyo pa kudya ndi kukonda zakudya, zida zodyera zinkawerengedwa ngati% ya chiwerengero cha 24-h (kcal) chomwe chinkadya monga mawonekedwe a chokoleti chokwanira chokoleti, chomwe chinkapezeka kuti chimakonda kwambiri maphunziro onse ( onani Zotsatira) ndipo ndi ziti zomwe zitchulidwa pano kuti ndi 'zakudya zokonda'.

 

Thupi la 1:

 

Kusiyanitsa kosiyana ndi kuyerekezera monga kudya kumakhala pamodzi.

Njira Yodyetsera

Baseline

 

Gulu losiyana la maphunziro (n= 15) inali yotsatiridwa ndi ndondomeko yotsatira ya tsiku ndi tsiku: 15 min min isanayambe mdima, nyama zidasamutsidwa kupita kuchipinda, kuyeza, ndi kuikidwa pamtanda (20 × 25 × 36 cm). Phunziro lililonse lidakhala ndi nthawi zinayi zotsatirazi: (a) 1-h chow kupeza, (b) 2-h chakudya chosowa, (c) 10 min access to chow feeder, ndi (d) 10- Kupita kwa min kwa chow odyetsa osiyana. Makoswe anabwezeredwa mofulumira ku khola la nyumba ndi vivarium ndi chow kupezeka ad libitum. Pa nthawi yoyambira ndi kuyesa, madzi analipo nthawi zonse ad libitum. Phokoso loyera (70 dB) linalipo mu chipinda choyesera. Zomwe 2-h imasungira zakudya (1) zimayambitsa yunifolomu yowonjezera, (2) yowonjezera zofuna zowonongeka, (3) zowonjezera zowonjezereka zogwiritsidwa ntchito kwa 10 ndi zotsatira zotsalira, ndipo (4) kuthandizira kupezeka kwapafupi kwa amakonda zakudya. Kuloledwa kunayesedwa ndi 0.01 g molondola. Zakudya zowonjezera zinkawerengedwa ngati kupuma kwa thupi (mg) pa unit (kcal) mphamvu yowonjezera. Pambuyo pa masabata ~ 2, kudya kwa 10-min feeders kunakhazikika, ndikuyamba kudyetsa chakudya chowonjezereka pamsana woyendetsa masewera ophunzirira masiku onse r=0.97, p<0.01) (Hartz Et al, 2001). Nthawi yoyambayi inasiyanitsa nthawi ya procurement acquisition / acclimation kuchokera ku zakudya zomwe amakonda kudya zomwe zimapangidwanso.

kuyezetsa

 

Poyesera, makoswe, ofanana ndi kulemera kwa thupi, chakudya choyenera tsiku ndi tsiku, chakudya choyenera, komanso kudya chakudya nthawi iliyonse ya masewero, adatumizidwa ku gulu la olamulira la 'chow / chow', lomwe linalandira chow kuchokera kwa onse ochepa omwe ali ndi 10 kapena 'chow / gulu' losankhidwa, lomwe linalandiranso chow m'dongosolo loyamba la 10 feeder, koma mmalo mwake adalandira zakudya zomwe amazikonda kwambiri mchigawo chachiwiri cha 10. Mphungu zinayesedwa tsiku ndi tsiku mpaka tsiku la 52, kupatula ngati zinafotokozedwa

Thupi la 2:

Makoswe okhala ndi phokoso lochepa, lochepa kwambiri lofikira zakudya zowonjezera, zowonjezera zakudya zidzawonetsa kuwonjezeka kwa nkhaŵa monga khalidwe.

Mtsinje waukulu kwambiri

Kuti mudziwe ngati makoswe omwe ali ndi vuto lochepa la chakudya chofunika kwambiri anayamba kuwonjezeka nkhawa-monga khalidwe, kuyesedwa kwapamwamba kwa-maze kunachitidwa pansi powala monga momwe tafotokozera poyamba (Zorrilla Et al, 2002). Njira zazikuluzikulu zinalipo peresenti ya nthawi yonse ya mkono ndi zolembera zomwe zinatsogoleredwa kumalo otseguka, zitsimikizirika zoyenera za khalidwe lachisokonezo (Fernandes ndi File, 1996) ndi chiwerengero cha zida zokhoma zitsekedwa, ndondomeko ya zochitika zotsatsa (Cruz Et al, 1994). Mphuno zomwe zafotokozedwa mu 1 zozizwitsa zinayesedwa 3-5 h mu mdima (~ 24-26 h pambuyo pofuna kudya zakudya) tsiku la test 16. Chigawo chodyera nthawi zonse sichinachitike lero.

Thupi la 3:

Chithandizo cha Nalmefene chidzasokoneza chakudya chokwanira malinga ndi zakudya zambiri.

Kuti mudziwe zomwe ntchito ya opioid receptor imapangitsa kuti makoswe adziwe bwino, makoswe adalandira nalmefene (0, 0.01, 0.03, 0.1, 0.3, 1 mg / kg, pang'onopang'ono (sc)) 20 min musanayambe mlimi woyamba wa 10. Nthawi yopititsa patsogolo imeneyi inasankhidwa kuti zitsimikizire ntchito yotsutsa yonse ponseponse kuwonetsera kwa onse odyetsa. Malipoti am'mbuyo amasonyeza kuti zimatengera 15-20 min kuti zotsatira zake zikhale zogonjetsa zowonongeka kuti ziwonedwe mu khola, ndi ntchito yofanana ndi yogwira ntchito ndi ex vivo malo ogwira ntchito amalandira osachepera 1 h (June Et al, 1998; Unterwald Et al, 1997; Landymore Et al, 1992). Mankhwalawa anaperekedwa kwa makoswe omwe anafotokozedwa mu 1 yopanga malemba pogwiritsa ntchito chilembo chokwanira cha Latin ndi 1 mpaka 3 masiku opimitsa mankhwala osapereka mankhwala kuchokera masiku 24 mpaka 37 akutsatira majekesiti atatu a tsiku ndi tsiku a acclimating saline.

Hypothesis 4

Makoswe okhala ndi phokoso lochepa, osakwanitsa kupeza zakudya zowonjezera, zowonjezereka zimakhala zowonongeka.

Kutulutsa leptin, GH, ndi 'yogwira' ghrelin

Kuti mudziwe ngati makoswe omwe ali ndi vuto lochepa la zakudya zopatsa thanzi lakhala lopweteka kwambiri, ndipo amayamba kusintha kwambiri kulemera kwake, makoswe amatha kudya msanga usiku wonse (18 h) ndipo amachepetsa 2-5 h mu mdima wotsatira tsiku la 53 pa ndondomeko ya zakudya. Mphungu zinaphedwa pambuyo pa yunifolomu 18-h mwamsanga pofuna kuchepetsa zomwe zingasokoneze zotsatira zoyipa zodyetsa, kuphatikizapo kusiyana kwa zochitika za mbiriyakale zomwe zimadya panthawi yoperekera kuyesera kapena pakhomo la nyumba. Poyesa makoswe kuti asamayende bwino, kukula kwa kusala kunali kosavuta pa caloric, mofanana ndi zomwe zinkagwiritsidwa ntchito kale kuti ziphunzire zinthu zoterezi mu makoswe (Proulx Et al, 2005; Dzenje Et al, 2006) ndipo zikufanana ndi ndondomeko ya chipatala cha kusala kudya usiku wonse pofuna kuyesa mahomoni awa mwa anthu (Foni Et al, 1998; Sherwin Et al, 1977). Magazi amtengo (~ 5 ml) adatoleredwa m'machubu ozizira okhala ndi 500 μl a 0.5 M ethylenediaminetetraacetic acid ndi 50 μl wamalonda a protease inhibitor (Sigma catalog P8340). Plasma idadzipatula ndi centrifugation (4 ° C, 3000 g, 15 min) ndi kusungidwa pa -80 ° C mpaka kafukufuku wowonongeka ndi immunoassays kwa rat leptin (LincoPLEX), GH ndi Ser³-n-octanoylated ghrelin (acyl-ghrelin) yolumikizidwa ndi ma enzyme (Linco, St Charles, MO). Malire azithunzithunzi anali 12, 500, ndi 33 pg / ml, motsatana. Ma coefficients a intra-assay a kusiyanasiyana ndi <5, <4, ndi 3.5-5.5%, motsatana.

Chidwi

Mitembo inali yotentha (kutentha kwapakati) ndipo inayesedwa kuti imvetsetse kuwonongeka kwa madzi oundana. Matenda a m'mimba amachotsedwa kuti adziwe kulemera kwake. Mankhwala a inguinal (subcutaneous) ndi gonadal (intra-m'mimba / visceral) amaphatikizidwa, kuyeza, ndi kubwerera ku nyama yowonongeka kwa mankhwala. Mafuta onse a thupi, mafuta ambiri, ndi mafuta opanda madzi (FFDM) adatsimikiziridwa kugwiritsa ntchito njira Harris ndi Martin (1984).

Chiwerengero cha Kusanthula

Kusintha kwa gawo loyeserera kudya komanso kuchuluka kwa chakudya kudawunikidwa pogwiritsa ntchito njira ziwiri zowerengera, poyambira ngati covariate. Kuchulukitsa kwakudya tsiku ndi tsiku komanso kunenepa kwa thupi kumawunikidwa pogwiritsa ntchito njira zowunikirira mobwerezabwereza za kusiyanasiyana (ANOVA). M'mitundu yonse iwiri, mbiri yazakudya inali pakati pa maphunziro ndi tsiku mkati mwa maphunziro. Wophunzira t-magwiritsidwe ntchito kutanthauzira kusiyana kwakukulu kwa gulu ndi kuzindikira kusintha kwa chiwerengero cha chakudya chokwanira ndi kulemera kwa thupi.

Kuti mudziwe ngati 'kupeza' kwa kudyetsa-monga kudya (Hagan ndi Moss, 1997) komanso zosiyana ndi zosiyana siyana (woyamba feeder chow hypophagia) zofanana ndi zomwe zimaphatikizapo kuphunzira, zotsatirazi zokhudzana ndi kugwiritsidwa ntchito kwazinthu zinayi zoyenera kudya (Hartz Et al, 2001):

 

Mitengo ndi mafayilo amadzipangira zakudya zowonjezera komanso zowonjezera pambuyo pa zakudya zomwe zimachitika m'mbiri ya anthu ('kuphunzira'). The Hillslope ikufotokoza mlingo ndi valence ya kusintha mavitidwe. The EC₅₀ imafotokoza chiwerengero cha masiku omwe adapitilira mpaka 50% ya kusintha kwakukulu kwa khalidwe.

Kuti mudziwe ngati makoswe amasiyana mosiyana ndi omwe ali ndi chiopsezo choyipa kapena kuyerekezera kudya, njira ziwiri, zotsatira zowonongeka zosagwirizana za mgwirizano weniweni (Kuphulika ndi Kutha, 1979) adachitidwa pazakudya zoyamba zowonjezera za 10 (kcal) za masiku 7 ku 15.

Kugonjetsa kwazitsulo kunagwiritsidwa ntchito kuti mudziwe ngati makoswe omwe ali ndi mwayi wosakwanira wopatsa zakudya adasintha nthawi zonse (r², chiwerengero cha kusiyana kwafotokozedwa) kapena chikhalidwe (kutsetsereka) kwa mgwirizano pakati pa chakudya choyamba ndi chachiwiri. Kugonjetsa kunkagwiritsidwanso ntchito kuyesa mgwirizano pakati pa "binge" (kukula kwa 2 kudya kwa masiku 7-15) ndi khalidwe lofanana ndi nkhawa, monga momwe zimayendera ndi% kutsegula manja.

Zotsatira za Nalmefene pakudya zidawunikidwa pogwiritsa ntchito njira ziwiri zobwereza za ANOVA. Mbiri yazakudya ndi mlingo wake zinali pakati- komanso mkati mwa mitu, motsatana. Kusiyanitsa kwapadera kumatsimikizira ngati zotsatira zamankhwala zimadalira molondola, komanso nalmefene's ED₅₀ Kuchepetsa kudya kwachiwiri (kudya ngati kudya) kuyerekezera kuti akugwiritsa ntchito sigmoidal dose-reaction function. Zotsatira zamankhwala awiriawiri zidatanthauziridwa pogwiritsa ntchito mayeso a Dunnett komanso momwe mbiri ya kadyedwe idapangidwira ndi Student's t-kuyesa. Kuyesedwa kwa Dunnett kunagwiritsidwa ntchito kuti adziwe ngati nalmefene imasinthiratu makoswe amtundu wa chow / okondedwa pamiyeso yamagalimoto oyendetsedwa ndi chow.

Kuti muwone tanthauzo loti hypophagia kwa wodyetsa woyamba atha kuwonetsa kuyankha kolipira kunenepa kwambiri, malumikizidwe a Pearson amawerengedwa pazoyambira komanso zotsalira kwa masiku 7-15. Kusanthula kumeneku kunatsimikizira ngati kulumikizana kosiyanako kulipo pakati pa kusiyanasiyana kwamphamvu ndi thupi limodzi (tsiku lomwelo) kapena pambuyo pake (kutambasulidwa ndi 1 kapena masiku a 2) kusiyanasiyana kwa kudya koyambirira kwa hypophagia (kofanana ndi koyambira) kumzake. Zolumikizana zidachitidwa mosasamala tsiku, pambuyo pa Fisher's Z kusinthika ndi kubwezeretsedwa kuti mupeze pafupifupi r. Chifukwa cha kusemphana kotheka kwa mgwirizano wanzeru wa tsiku ndi tsiku, kuyanjananso kunayanjanitsanso kugwirizana kwa tsiku la 3 tsiku loyendetsa phindu la thupi ndi nthawi ya 3 yomwe imayenda pamasewera a chow hypophagia.

Kukondera, kuchuluka kwa plasma metabolite / mahomoni, ndi njira zowonjezerapo zidawunikidwa pogwiritsa ntchito Wophunzira wopanda wopanikizika kapena wophatikizika t-kuyerekezerani pakati pa- kapena mkati-zofanizira mitu, motero. Mapulogalamuwa anali Systat 11.0 (SPSS, Chicago, IL), SigmaPlot 9.0 (Systat Software, Inc., Point Richmond, CA), InStat 3.0 (GraphPad, San Diego, CA), ndi Prism 3.0 (GraphPad).

Pamwamba pa tsamba

ZINTHU

Kukonda Zakudya

Zomwe zimatanthauza (± SEM) chiwerengero cha 24-h (kcal) chiwerengero cha chokoleti chokondedwa, chokwanira kwambiri cha sucrose pa zakudya za chow chinali 92.2 ± 1.1% (zosiyana: 88.8-97.9%).

Thupi la 1:

Kusiyanitsa kosiyana ndi kuyerekezera monga kudya kumakhala pamodzi.

Oyimira 10 min Miners

Monga ananeneratu, makoswe omwe amapeza kuchepa kwa chakudya chofunika kwambiri (chow / chosankha) amapanga hypophagia ya chow kuchokera ku 10-min feeder yoyamba (Chithunzi 1a; Mbiri ya zakudya: F (1,12) = 14.48, p<0.005; Mbiri yazakudya × tsiku: F (14,168) = 2.29, p<0.01) ndi hyperphagia yazakudya zomwe mungakonde kuchokera kwa wodyetsa 10-min wachiwiri (Chithunzi 1b; Mbiri ya zakudya: F (1,12) = 53.96, p<0.001; Mbiri yazakudya × tsiku: F (14,168) = 8.98, p<0.001). Kudyetsa kusintha kumadalira luso, monga zikuwonetsedwera ndi mbiri yazakudya × kulumikizana kwamasana ndipo, makamaka ndikuyenera kwa chakudya kuchokera kwa wodyetsa aliyense kupita ku sigmoidal Associative kuphunzira ntchito (Chithunzi 1c, Gulu 2). Njira ziwirizi sizinali zosiyana zokhazokha, komanso maulendo osiyanasiyana komanso nthawi. Kupeza chakudya chokwanira (kudyetsa 2) kunadutsa ndipo kunayamba kutsogolo kwa chow hypophagia (chakudya chodyetsa 1). Magulu a mbiri ya zakudya amasiyana mosiyana kuchokera tsiku ndi tsiku 2 kwa chakudya cha 2 (amakonda zakudya hyperphagia), koma osati tsiku la 9 la chakudya cha 1 (chow hypophagia). The EC₅₀ chifukwa chodziletsa monga hyperphagia zisanachitike kuti 'zoyembekezera' chow hypophagia ndi masiku 4-5 (Gulu 2).

 

Ngakhale makoswe a chow / chow anadyetsedwa pafupi ndi chakudya choyamba cha ~ 6 kcal, kusonyeza kudya pang'ono (~ 1 kcal) kuchokera kumadyetsa achiwiri (Chithunzi 1b), makoswe ochepetsedwa / okondedwa omwe adakondweretsedwa adayambanso kudya chakudya chachiwiri kwa 34.4 kcal. Motero, 42.9 ± 2.0% ya kudya tsiku ndi tsiku (kapena 45.6 ± 2.7% ya chow / chow kudya tsiku ndi tsiku) ankadyetsedwa mkati mwa 10 min peresenti imodzi ya 45 mg papepala chakudya chilichonse 2.9 ± 0.1 s (zosiyana: 151-259 pellets / 10 min). Mosiyana ndi zimenezi, chakudya choyamba chodyera chochepa chinachepa mpaka 3.4 kcal (61% ya chakudya choyambirira choyamba kudya).

Kulemera kwa thupi ndi chakudya choyamba chogwiritsira ntchito

Mu chow / makoswe okondedwa, kupindula kwakukulu kwa thupi sikunagwiritsidwe ntchito panthawi imodzi kapena kuneneratu kuti hypophagia yochuluka kwambiri poyambira kuyambira masiku 7-15, r= 0.102) kapena mgwirizano wamkati pakati pa izi (pafupifupi r's = 0.022 ndi -0.040 ya 1- ndi 2-day lags, motsatana). Momwemonso, kulemera kwapakati kwa makoswe panthawiyi sikunkagwirizana ndi kukula kwake koyamba kwa hypophagia (pafupifupi r= -0.025).

Kusiyanitsa kwa munthu aliyense ndi kuyerekezana kwa mgwirizano

Mosiyana ndi kusowa kwa ubale wa kulemera kwa thupi kwa odyetsa oyamba hypophagia, intraclass correlation analysis inasonyeza mphamvu, yosasunthika payekha pa kudya kwa makoswe okonda /ICC[2,9] = 0.86, r²= 0.74; F (7,56) = 7.93, p<0.00001) ndi wodyetsa wachiwiri (ICC[2,9] = 0.89, r²= 0.79; F (7,56) = 9.42, p<0.00001). Mosiyana ndi izi, makoswe odyetsedwa ndi chow sanawonetse kusiyana kulikonse pakudya koyambirira (ICC[2,9] = 0.37, r²= 0.14; F (6,48) = 1.61, p= 0.17) ndi kusiyana kwakukulu kwa munthu wodwala chakudya chachiwiri (ICC[2,9] = 0.64, r²= 0.41; F (6,48) = 2.78, p<0.05). Chifukwa chake, atasowa pang'ono, makoswe odyetsedwa / chow adadyetsedwa m'njira yodziyimira payokha payokha. Mosiyana ndi izi, makoswe odyetsedwa okondera adawonetsa mawonekedwe, makulidwe ena enieni a 'choyembekezera' chow hypophagia ndikusankha zakudya za hyperphagia kutsatira mphamvu zochepa.

Ngakhale kudyetsa makoswe a mtundu wa chow / chow anali wodalirika kwambiri komanso wothandizira kwambiri kudyetsa (otsetsereka = 0.78, wodalirika kwambiri kuposa 0, F (1,5) = 11.67, p<0.02), mogwirizana ndi kukonzanso kosalekeza, kunalibe kulumikizana kodalirika pakati pa kudya makoswe amtundu wa chow / okondedwa kuchokera ku chow kupita ku chakudya chodyera (kutsetsereka kosazindikirika kuchokera ku 0, F (1,6) = 1.07, p= 0.34) (onani Chithunzi 1f, kusiyana mu r², z= 2.43, p= 0.01]). Choncho, kudya kwa makoswe okhaokha / osakondwera sanawonetsetse kapena kulimbana ndi mphamvu za 'homeostatic / compensatory' zochepa panthawi ya zakudya / feeders. Nkhani zomwe zinasonyeza kuti chowopsa kwambiri chow hypophagia sizinali zomwe zimasonyeza kuti ndizoopsa kwambiri monga hyperphagia.

Kukonzekera kwa 1-h chow kudya

 

Nkhumba zowonongeka 1-h chow kudya za makoswe okhuta / odyetsedwa omwe adakondweretsedwanso anachotsedwa kwambiri kuyambira kuyambira tsiku la test 11 (Chithunzi 1d; mbiri ya zakudya × kugwirizana kwa tsiku F (14,182) = 2.35, p<0.01). Komabe, kuchepa kwa kudya kwa 1-h chow kudya kunayambanso kuyamba (tsiku la 11 vs tsiku 9) ndipo ndizochepa kwambiri palimodzi (t(7) = - 5.59, p<0.001) ndi mawonekedwe ofanana (t(7) = - 3.00, p<0.01) kuposa kuchepa kwapakati pazakudya zodyetsa zoyambirira zomwe zimawonedwa mu makoswe a chow / omwe amakonda. Chofunika kwambiri, zomwe apezazi ndizogwirizana ndi 'kuyembekezera' kutanthauzira kwa woyamba kudyetsa hypophagia ndipo, monga kusowa kwa kulumikizana ndi kunenepa kwa thupi, zosagwirizana ndikumasulira kwina komwe woyamba kudya hypophagia adachokera kumayankho otsalira a mphamvu ya homeostatic pakudyetsa asanadye kapena kulemera kwambiri phindu.

Chakudya cha kunyumba-cage chow

 

Kunyumba-cage chow kudya za makoswe / zakudyetsedwa-pang'onopang'ono zimachepa pang'onopang'ono (mwadongosolo)Chithunzi 1e; Mbiri ya zakudya: F (1,12) = 100.64, p<0.001; mbiri yazakudya × tsiku: F (14,168) = 12.06, p<0.001), makamaka patsiku lakuyesa la 3.

Kugwiritsa ntchito tsiku ndi tsiku

 

Ngakhale kusintha kwakanthawi pakudya kwakanthawi patsiku, ANOVA sanawulule zovuta zamakedzedwe azakudya kapena mbiri yazakudya × tsiku pakuwonjezera mphamvu zamagetsi tsiku ndi tsiku. Komabe, Student's t-zinthu zinawonetsa kuti mphamvu yowonjezera ya makoswe odyetsedwa / odyetsedwa bwino, koma kwambiri, idapambana kuposa makoswe a chow / chow odyera kuyambira tsiku loyesa 9 (Chithunzi 1g).

Thupi la 2:

 

Makoswe okhala ndi phokoso lochepa, lochepa kwambiri lofikira zakudya zowonjezera, zowonjezera zakudya zidzawonetsa kuwonjezeka kwa nkhaŵa monga khalidwe.

Makoswe a Chow / odyetsedwa omwe adasankhidwa anawonetsa kwambiri kuchepa kwa nthawi yochepa (Chithunzi 2a, kumanzere) ndi kulowa mkati (kutanthauza ± SEM: 21.5 ± 4.6 vs 34.7 ± 4.7%; t(13) = 2.14, p<0.05) manja otseguka a kuphatikiza-maze poyerekeza ndi makoswe odyetsedwa ndi chow / chow, nkhawa ngati nkhawa. Chiwerengero cha zolembera pamanja, gawo loyang'anira zochitika za oyendetsa (Cruz Et al, 1994), sanasinthidwe ndi mbiri ya zakudya (Chithunzi 2a, kumanja). Kukula kwamakoswe komwe kumalumikizidwa kwambiri ndimachitidwe ake ngati nkhawa, akuwonetsedwa pakuphatikizika kwakukulu pakati pa kudya kwa 2 wodyetsa komanso% nthawi yotseguka yamphongo ya chow / makoswe (Chithunzi 2b). Ubalewu umakhala ndi kusiyana kwakukulu pakati pa miyeso iyi (77.4%) ndipo sizinali zofunikira pofufuza ndondomeko za makoswe a chow / chow mosasamala kanthu kuti kunja kunaphatikizidwa (36.5%) kapena kutayidwa (9.2%).

 

Thupi la 3:

 

Chithandizo cha Nalmefene chidzasokoneza chakudya chokwanira malinga ndi zakudya zambiri.

Pansi pa chithandizo cha galimoto, makoswe odyetsedwa / odyetsedwa ankakonda 'kuyembekezera' chow hypophagia (feeder 1) ndipo ankakonda kudya hyperphagia (feeder 2) (Chithunzi 3). Monga ananenedweratu, mankhwala osokoneza bongo amachititsa kuti thupi la 10 min chow lidye kuchokera kwa oyamba kudya malinga ndi zochitika m'mbiri (chakudya chambiri × dose: F (5,65) = 3.60, p<0.01; mlingo: F (5,65) = 3.06, p<0.05). Makamaka, nalmefene yachepetsa kudya makoswe odyetsedwera a chow / chow mu njira yolowera, yodalira mlingo (F (1,30) = 13.35, p<0.001), ndikuchepetsa kwakukulu pamagalimoto omwe awonedwa pamiyeso ya 0.03 ndi 1 mg / kg. Mosiyana ndi izi, nalmefene idakulitsa kwambiri kudya makoswe a chow / okonda kudya pamlingo wa 0.03 mg / kg (Chithunzi 3, kumanzere). Chifukwa chake, kuchepa kwa mlingo wochepa (sc, 0.03 mg / kg) watseka 'kuyembekezera' chow hypophagia.

 

Nalmefene nayenso amasiyanitsa chakudya chochokera kuchigawo chachiwiri malinga ndi zakudya zambiri (zakudya zambiri × dose: F (5,65) = 6.60, p<0.001; mlingo: F (5,65) = 6.28, p<0.001). Makamaka, nalmefene mwamphamvu (ED₅₀= 0.025 mg / kg, r²= 0.97) ndi kudya kwapadera kwa chakudya chofunidwa ndi makoswe a chow / okondedwa omwe ali okonda kudya, muzowonongeka ndi mlingo (F (1,30) = 35.37, p<0.0001), osasintha molondola kudya makoswe a chow / chow ()Chithunzi 3, pakati).

Mogwirizana ndi izi zowonjezera, mankhwala osokoneza bongo amasiyanitsa mosiyana thupi lonse la 20 yomwe idalowa m'magulu awiriwa, omwe amasonyezedwa ndi onse (F (5,65) = 5.31, p<0.0001) ndi kusiyanasiyana kwapadera (F (1,13) = 44.68, p<0.0001) mbiri yazakudya × zotsatira zolumikizana. Nalmefene amachepetsa kwambiri kudya makoswe a chow / okondedwa ndi a chow / chow (log-linear: otsetsereka: -4.05 ± 0.94 vs -0.69 ± 0.32 kcal / mlingo increment, motsatira). Nalmefene nayenso amachepetsa mofulumira thupi lonse la 20 lomwe linalowa mu chow / makoswe okonda (dose: F (5,35) = 8.48, p<0.0001), kuchepetsa kudya kwambiri pa 0.1, 0.3, ndi 1 mg / kg doses, pomwe mlingo wokhawo (1 mg / kg) ndiwothandiza pa makoswe a chow / chow (mlingo: F (5,30) = 2.70, p<0.05). Ponseponse, mlingo waukulu kwambiri wa nalmefene (1 mg / kg) unachepetsa kuchuluka kwa mphindi 20 za makoswe omwe amadyetsedwa / osankhika mpaka pamlingo wopitilira modzidzimutsa pakuwongolera kwamagalimoto a chow / chow-fed (Chithunzi 3, kumanja). Thandizo la Nalmefene silinapangitse zotsatira zowonongeka pa tsiku loyamba kapena lachiwiri lokhala ndi chakudya chamasiku opatsirana.

Thupi la 4:

 

Makoswe okhala ndi phokoso lochepa, osakwanitsa kupeza zakudya zowonjezera, zowonjezereka zimakhala zowonongeka.

Kupindula kwa thupi ndi chakudya choyenera

 

Makoswe a Chow / odyetsedwawo amapeza thupi lolemera kuposa makoswe a chow / chow (chakudya chambiri: F (1,13) = 10.79, p<0.01; mbiri yazakudya × tsiku: F (14,182) = 5.96, p<0.001). Kusiyanitsa kwakukulu kwamagulu kudawonekera patsiku 5 (masiku 4 masiku asanakwane mphamvu zowonjezera), kuwonjezeka patsiku la 15 (Chithunzi 4a). Patsiku 15, makoswe odyera / odyetsedwa omwe anapatsidwa anali a 14.3 kwambiri kuposa makoswe a chow / chow odyetsedwa ngakhale kuti anali atangowonjezera 92 kcal kwambiri ndipo analandira 2.5 yekha kupeza chakudya cha dzuwa. Phindu lolemera powonjezera mphamvu zowonjezera mphamvu likuwonetsa kuwonjezeka kwa kuwonjezeka kwa chakudya chokwanira (Chithunzi 4b), zomwe zinali zosiyana kwambiri ndi mbiri ya zakudya (F (1,12) = 10.14, p<0.01) patsiku 5. Pofika masana 24, makoswe oyamwa / okondedwa omwe amayeza amalemera kwambiri kuposa makoswe odyetsedwa / chow (Chithunzi 5a), ndipo anali 11% olemera patsiku la 53 (ngakhale atalandira kokha ~ 9 mpata wokwanira wa zakudya zomwe amakonda).

 

Chidziwitso ndi chikhalidwe cha endocrine

 

Kulemera kwa thupi kwakukulu kwakukulu chifukwa cha kuwonjezeka kwa 57% mu mafuta ambiri (Chithunzi 5b, kumanzere). Choncho, makoswe odyetsedwa / odyetsedwa anali olemera kwambiri, monga momwe akufotokozera kuwonjezeka kwakukulu kwa% mafuta a thupi, osasinthika ndi chiwerengero cha kulemera kwa thupi komwe kunawerengedwa ndi FFDM (Chithunzi 5b, kumanzere) ndi kuchepa kwa madzi% (kutanthauza ± SEM: 71.9 ± 0.8 vs 74.3 ± 0.7%, p<0.05). Kusanthula kwamafuta pad kuwonetsa kuwonjezeka kwakukulu kwa ma subcutaneous (inguinal; kuwonjezeka kwa 41%) ndipo, makamaka, visceral (gonadal; 76% yowonjezera) malo osungira mafuta (Chithunzi 5, kumanja).

Mphuno ya pulasitiki, makoswe ochepetsedwa / odyetsedwawo amasonyezanso 60% yapamwamba leptin-immunoreactivity, 47% yochepa GH-immunoreactivity, ndi 59% low acylated ghrelin-immunoreactivity, poyerekeza ndi makoswe a chow / chow (Chithunzi 6a-c). Malingana ndi kuyembekezera, plasma leptin-immunoreactivity imagwirizana kwambiri ndi mafuta onse mkati mkati (rs = 0.82 ndi 0.86 kwa magulu a chow / omwe amakonda / ps <0.05) komanso m'magulu onse (r= 0.91, p<0.001) (Chithunzi 6d) komanso ndi gonadal (r= 0.85, p<0.001) ndi misala yamafuta inguinal (r= 0.78, p<0.01).

Pamwamba pa tsamba 

KUKANGANANI

Amphaka achikazi omwe ali ndi mwayi wambiri wopeza zakudya zabwino kwambiri, zakudya zamtundu wa sucrose wambiri amadalira zodziwa zambiri, kudya zakudya zolimbitsa thupi komanso zakudya zina zosayenera. Zomwe zimagwirizanitsa ndi khalidwe la kudyetsa zinali zosasokonezeka kwa wina ndi mzake pakapita nthawi, pa anthu onse, komanso mu mankhwala awo a mankhwala-kuyankhidwa kwa wotsutsana ndi opioid-receptor, posonyeza kuti amaimira njira zosiyana-siyana zomwe zimakhudzidwa ndi zolemba zina. Makoswe okhala ndi chakudya chosafunika kwambiri amasonyezeranso kuwonjezeka kwa nkhaŵa ngati khalidwe ndipo mwamsanga anafika povuta kwambiri.

Kudya mofanana ndi kudya kunakula mofulumira (EC₅₀= Masiku a 3.2) pa ntchito yowonjezera, yogwirizanitsa ndi wophunzira, wothandizana nawo (Hartz Et al, 2001). 'Binges' inali yaikulu, imawerengera pafupifupi theka la caloric tsiku kudya ndipo anali ~ 7 kupitirira kuposa caloric kudya amene anatha kusunga chow-kusunga makoswe ochepa nthawi (2 h) nthawi. Pa masiku oyambirira a 8 a kuyesedwa (pamene chow hypophagia anali asanayembekezere), 'mabango' adachitika ngakhale kuti makoswe anali atangodya kumene kusakaniza zochuluka za chow kuchokera pa odyetsa oyamba. Pa tsiku lotsatira, mlingo wa chiyembekezero chow hypophagia sudzafika pa mlingo wa kudya mopitirira. 'Binges' inadalitsidwa ndi mlingo wodalirika ndi mlingo wochepa kwambiri wa zovuta (zofanana ndi zomwe zimagwiritsidwa ntchito m'mabuku), μ/κ Otsutsana ndi opioid-receptor omwe amalepheretsa kumwa mowa wambiri mowa mwauchidakwa (Mason Et al, 1994, 1999) ndi zomwe zimachepetsanso kugwiritsidwa ntchito ndi "zosangalatsa" za chakudya chokoma mwa anthu (Achiyese Et al, 1990; Amatsenga ndi Oyera, 2002; Amayi ndi Wright, 1991). Mphaka idadya mofulumira m'mabinges (~ 2.9 s / 45 mg pellet popanda kuwononga nthawi yopanda kudya), mofulumira kuposa makoswe ad libitum pa zakudya zomwezo zomwe amakonda (zosasindikizidwa). Zomwe zapezazi zikuwonetsa kuti gawo la hedonic pazomwe zimadya ngati chakudya. Chosangalatsa ndichakuti, chidwi chokhala ndi chizolowezi chodya mopitirira muyeso chinali chikhalidwe chokhazikika, chazokha, chokhala ndi chidziwitso cha nkhaniyi kwa 79.7% ya kusiyanasiyana kwakukula kwakanthawi kwakanthawi kopezeka.

Ngakhale kuti kudya monga kudya kumapangidwira zakudya zopanda malire, zakudya zopatsa thanzi, makoswe ochepetsedwa / ochepetsedwa amachepetsa kudya zakudya zosafunika kwambiri m'nyumba zawo zapakhomo komanso poyerekeza ndi nthawi yotsatila (gawo loyamba). . Kuyamba kwa ma hypophagias ameneŵa kunasiyana, ndi chow hypophagia m'nyumba ya khola (tsiku 3) yomwe idatsogoleredwa ndi oyambira oyambirira (tsiku 9) ndi nthawi yowonongeka (tsiku la 11) panthawi ya 1 sabata. Maphunziro sanapangidwe kuti azitha kusiyanitsa njira zothandizira kuchepetsa ngongole kapena chakudya chokonzekera. Komabe, zofukufuku zingapo zimathandizira kutanthauzira kuti chow hypophagia pa odyetsa oyamba anali mawonekedwe osaganizira zosiyana (Flaherty ndi Checke, 1982; Flaherty ndi Rowan, 1986; Flaherty Et al, 1995) komanso osati mphamvu ya homeostatic malipiro owonjezera kulemera, kupitirira malire, kapena kusiyana kosiyana. Choyamba, panalibe mgwirizano wofanana kapena woyembekezereka pakati pa kusiyana kwa kulemera kwake ndi kukula kwa chow hypophagia (mosiyana ndi kusiyana kwakukulu komwe kumawoneka mu chow hypophagia). Chachiwiri, choyamba chodyetsa chow hypophagia chinayamba masiku a 2 kale ndipo chinali chachikulu kwambiri kuposa hypophagia pa nthawi yoyamba yowonongeka. Nzeru za homeostatic zikananeneratu kuti zimakhala zofanana ndi kukula kwake (ngati sizikufulumira komanso kukula kwakukulu) za anorexia panthawi yoyamba yowonongeka, ngati chiwerengero chodziwika bwino chapadera chikaperekedwa mwachangu poyambira. Chachitatu, panalibe mgwirizano wosiyana pakati pa mlingo wa choyamba chodyera chowombera ndi kukula kwa mapiko odyetsa achiwiri. Chachinayi, choyamba chodyetsa hypophagia (EC₅₀= Masiku a 7.5) apangidwa ~ masiku 4-5 pambuyo pa kudya monga kudya. Mogwirizana ndi zotsatira zowonongeka, kuyerekezera kosaganizira molakwika chifukwa cha yankho lovomerezeka losavomerezeka limapezeka popanda kulemera kwa thupi kapena kusintha kwa caloric, pamene njira yothetsera mbiriyo ikupambana ndi njira yowonjezera yosakaniza (Flaherty ndi Rowan, 1986). Komabe, njira yothetsera mphamvu ya homeostatic yomwe ingathandize kuti pakhale chakudya chovomerezeka mu phunziro lino silingatheke. Mwachitsanzo, m'magulu a leptin ndi ghrelin, mavitamini ovomerezeka a homeostatic mahomoni omwe amatsogolere mphotho ya neurocircuitry (Hommel Et al, 2006; Abizaid Et al, 2006; Hao Et al, 2006; Shizgal Et al, 2001) amasiyana chifukwa cha zochitika zambiri komanso mwinamwake kusinthidwa kusanayambe kusiyana kwa kulemera kwa thupi. Kufufuza kwa nthawi yaitali za ma leptin ndi ghrelin kapena kugwiritsidwa ntchito kwa mankhwala kuchitapo kanthu kungathandize kufotokoza zopereka zilizonse za mphamvu zotere za homeostatic zowonongeka kuti zikhale zoyembekezereka pulogalamu yopita kuchipatala.

Mofanana ndi kumwa mowa, makoswe amodzimodzi amasiyana mofanana ndi momwe amachitira zosiyana zosiyana, ndi chiwerengero cha zizindikiro za 74.3% za kusiyana kwa kudya koyamba. Chofunika kwambiri, komabe, chikhalidwe ichi sichinali chokhudzana ndi chiwerengero chomwe chimakhala chosagwirizana ndi nthawi yomwe ikukhalapo kusiyana ndi kudya zakudya zolimbitsa thupi. Komanso, pamene vuto logwiritsira ntchito log-line logly linearly ndi monophasically kuchepetsa kudya-monga kudya ndi ED₅₀ ya 0.025 mg / kg ndi pafupi kuyimitsa chakudya chokwanira pa 1 mg / kg mlingo, wotsutsana ndi opioid analetsa kusiyana kosayembekezereka pokhapokha pa mlingo umodzi (0.03 mg / kg).

Chow kuyembekezera chow hypophagia kuchokera kwa odyetsa oyamba akukula chifukwa cha sigmoidal logistic kukula ntchito, zogwirizana ndi ophunzira, njira yogwirizana (Hartz Et al, 2001). Umboni uwu kwa munthu wothandizana nawo, wodziwa kusintha kwake ndi wosagwirizana ndi zifukwa zambiri zomwe zingakhalepo, kuphatikizapo kuti panalibe kusintha kwa nthawi, kuti kuphunzira kunali kosagwirizana ndi chirengedwe (mwachitsanzo, kuteteza kapena kuzoloŵera zakudya kapena zovuta) kapena ena osaphunzira kusintha (mwachitsanzo kusintha kwa kukula kwa mmimba, kusintha kosasintha kwa Pavlovian mu mphamvu ya homeostatic hormone action). Zambiri zingakhale zogwiritsidwa ntchito ngati zowonongeka za chakudya chofunika kwambiri, kuphatikizapo experimenter, malo oyesa, nthawi yoperewera, kapenanso chowonetserako choyamba cha feeder (chow). Inde, hyperphagia inali yotsika kwambiri (10.9 kcal, kapena 34%, zochepa, p<0.001) ngati wodyetsa woyamba sanaperekedwe, mogwirizana ndi gawo lomwe adapeza polimbikitsanso pokonza kapena kuwongolera kudya komwe akukonda (zomwe sizinawonetsedwe). Kuwongolera zoyeserera zoterezi zitha kukhala zothandiza kusiyanitsa pakati pazinthu zopanda chiyembekezo ndi zomwe zili ndi chakudya cha hyperphagia ndi magawo awo amitsempha.

Ndime, a μ/κ Otsutsana ndi opioid-receptor, omwe amalephera kuchepetsa zakudya monga hyperphagia ndizovomerezeka ndi zochitika zam'mbuyomu kuti mapulogalamu a opioid amatha kusungidwa ndi hedonic, osati chakudya chopatsa thanzi, chomwe chimakhudza anthu ndi nyama (Olszewski ndi Levine, 2007). Zofufuza zingapo zapitazo zimatsimikizira lingaliro lakuti mapulogalamu opatsa mphamvu opioid opioid amachititsa mayendedwe amakhalidwe opatsa mphoto, kuphatikizapo kudya moyenera mwa zakudya zopatsa chidwi (Kelley Et al, 2002). Nalmefene angakhale atasokoneza binge monga kudya ndi kuteteza opioid receptors mu ventral tegmental m'dera, motero amachotsa GABAergic zivomezi zotsekemera zomwe zimagwirizana pa dopamine neurons ndi kuchepetsa dopamine kumasulidwa mu chipolopolo cha nucleus accumbens (Taber Et al, 1998; Macdonald Et al, 2003, 2004). Nalmefene nayenso akanatha kuchita mwa kutseka μ-opioid receptors mu nucleus accumbens shell kapena ventral pallidum (Woolley Et al, 2006; Ward Et al, 2006), zigawo zogwirira ntchito za chipangizo cha tizilombo toyambitsa matenda kuti tikulitse mayankho okhutira ndi zakudya zomwe timakonda, zinthu zoponderezedwa, ndi zina mphoto (Smith ndi Berridge, 2007; Kelley Et al, 2005).

Kusiyanitsa kolakwika kumatanthauziridwa mosiyana ndi: Kusanthula (komwe mtengo wa hedonic wa choyambirira choyamba umachepa chifukwa cha mbiriyakale kapena zofanizira zowonetsera kwa chokondweretsa kwambiri), kulepheretsa (komwe makoswe amadziwa kuti chokoma kwambiri choyandikira chiri pafupi ndi mofanana kulepheretsa kudya kwapadera, kowonongeka, kosavuta), kapena mpikisano wamakhalidwe (momwe chizoloŵezi choyembekezera chimasokoneza kumeza kwa choyambirira choyamba) (Flaherty Et al, 1995). Ngakhale kuti deta yamakonoyo siyikusiyanitsa pakati pa kutanthauzira uku, imasonyeza kuti pulogalamu ya hedonic, yomwe ilibe mphamvu yowonjezera mphamvu zosiyana siyana. Choyamba, chow hypophagia choyembekezereka chinachitika ngakhale kuti 2 yapitayi yotsalira chakudya, kenako imatha kuyembekezera kuti nyama izilandira chakudya chokhala ndi mphamvu. Zomwe akupezazi zikugwirizana ndi zomwe zikuwonetseratu kuti zakudya zowonongeka zimapangitsa kuti zitha kuyanjana (Hunt Et al, 1988; Kauffman Et al, 1995).

Chachiwiri, mlingo umodzi wotsika wa 0.03 mg / kg) unalepheretsa choyembekezereka chow hypophagia mwa kuwonjezeranso kuvomereza chowonda chocheperako, komabe pang'onopang'ono kuchepetsa kudya kwa makoswe omwe sanayambe akudya zakudya zosakondera. Zosiyana ndi zomwe zimachitika pa chow kudya monga momwe mbiri ya zakudya imathandizira lingaliro loti opioids imathandizanso kuyanjana ndi ophunzira, njira zokhutiritsa zomwe zimapangitsa chakudya kulandiridwa ndi kusankha (Barbano ndi Cador, 2006; Jarosz Et al, 2006; minofu Et al, 2004). Izi zikhoza kusiyana ndi malingaliro ambiri omwe otsutsa opioid-receptor amangokhala anorectic pa se (makamaka chakudya chokoma) kapena kuika zakudya zowonjezera zakudya (intrinsic) hedonic (Cooper, 2004; de Zwaan ndi Mitchell, 1992).

Makoswe omwe sanalandire kwambiri shuga, zakudya zomwe amakonda kwambiri zokha zinangowonjezera nkhawa ngati tsiku la 1 atapeza chakudya chaposachedwa kwambiri. Kukula kwamakoswe komwe kumalumikizidwa kwambiri kumalumikizidwa kwambiri ndi momwe zimakhalira ngati nkhawa. Kaya machitidwe ofanana ndi nkhawa amakhala chifukwa chodya chakanthawi yayitali kapena kusiya kwambiri (Cooper, 2004) kuchokera ku zakudya zosakondedwa sizidziwika. Kupeza chakudya chokhazikika pa se ndipo posachedwa hypophagia sizingatheke chifukwa cha kuwonjezeka kwa nkhaŵa-monga khalidwe chifukwa chokonzekera chakudya chosowa chinawonjezereka poyera kutsegula mkono muzowonjezereka-maze, ndi nkhawa-like effect (Inoue Et al, 2004). Mofananamo, kunenepa kwambiri sikungathe kuwerengera nkhaŵa yowonjezereka-monga khalidwe chifukwa Zucker wotsamira ndi makoswe ovuta sizimasiyana mosiyana ndi khalidwe la maze (Chaouloff, 1994) ndipo chifukwa chosavuta kudya zakudya zopatsa thanzi komanso makoswe osagonjetsa zakudya sizikusiyana mosiyana m'maganizo (Levin Et al, 2000). Funso lofunika kwambiri pa phunziro la mtsogolo ndiloti khalidwe lodzidetsa nkhaŵa lomwe limasonyezedwa ndi makoswe a chow / osankhidwa amapezeka chifukwa cholandira chakudya pa se, mosiyana ndi zochepa kapena zazing'ono zopezeka. Zonsezi, zotsatira zake zimasonyeza kuti makoswe okhala ndi chakudya chosafunika kwambiri sankakonda kudya, koma mofananamo amakhala ndi nkhawa zambiri, zomwe zimagwirizana ndi kusokonezeka kwa matenda odyera kudya ndi kunenepa kwambiri pambali imodzi ndi nkhawa pa zina (Gluck, 2006; Kessler Et al, 1994; Mkonzi Et al, 1994).

Mphuno zopanda zakudya zochepa zomwe zimakonda kudya zimapangitsa kuti thupi likhale lolemera komanso mafuta sagwiritsidwa ntchito poyerekeza ndi kuchuluka kwa mphamvu zomwe zimagwiritsidwa ntchito, zomwe sizingathe kuwerengedwa ndi nthawi yonse yomwe amalandira ku chakudya chofunikila (~ 9 h). Zakudyazo zinali ndi mafuta ofanana, mapuloteni, ndi magawo ofanana, kotero kusiyana pakati pa macronutrient composition sikufotokoza zotsatira zake. Ngakhale kuti amadya mphamvu ya 8.3% yambiri, makoswe okhala ndi chakudya chochepa chokha anapeza 71.3% kulemera kwa thupi pa masiku 15. Pamapeto pa phunzirolo, makoswe okhuta / odyetsedwa omwe adalandirapo 88% yowonjezera thupi, chifukwa cha kuwonjezereka kwa mafuta a thupi, omwe amachititsa ngozi ya matenda a mtima ndi matenda a shuga (Kutha, 1993; Wajchenberg, 2000). Nthenda yowonjezera yowonjezera ya makoswe odyetserako angapangidwe kuchokera ku sucrose zomwe zili ndi zakudya zokondedwa (Kanarek Et al, 1987; Kanarek ndi Orthen-Gambill, 1982) komanso chizoloŵezi chodziwika chowononga mphamvu zazikulu zamagetsi zotsatizana ndi nthawi yokhayokha ya hypophagia (Batista Et al, 1997). Mtundu wodzisankhira wokhawokha wa chakudya chokhazikika umadodometsedwa mosadodometsedwa ndi chakudya chimodzi chokha cha kudya / zakumwa zoledzera kudya zakudya za ena a dieters ndi odwala matenda ovutika kudya, komanso ndi mayankho akuluakulu a insulin (Calderon Et al, 2004; Taylor Et al, 1999), akhoza kulimbikitsa lipogenesis.

Makoswe omwe analandira kwambiri kuchepa kwa chakudya chofunikiranso anapanga kusintha kwa endocrine komwe kunkaoneka mu kunenepa kwaumunthu, kuphatikizapo kuchulukitsa kuzungulira leptin (Considine Et al, 1996) ndipo adachepetsa kusakaza Ser³-n-octanoylated ghrelin magulu. Leptin, a ob gel product, ndi 16-kDa, makamaka woyera adipose minofu-yochokera hormone yozungulira (Bates ndi Myers, 2003; Guha Et al, 2003; Peak Et al, 2003) zomwe zimakhala ngati zizindikiro zosayenerera zowonetsera mphamvu ya mphamvu. Chifukwa chokhala ndi mafuta owonjezereka, kuyendetsa mawere a leptin kumawonjezeka kuti athetse chilakolako chofuna kudya ndi kugwiritsa ntchito mphamvu zamagetsi (Bates ndi Myers, 2003). Choncho, mu phunziro lino, maulendo a leptin akuwonjezeka ndipo amagwirizanitsidwa kwambiri ndi kuchuluka kwathunthu mafuta misa (Considine Et al, 1996; Maffei Et al, 1995). Mosiyana ndi leptin, ghrelin, tsamba la 28, lomwe limasinthidwa pambuyo pake, lokhazikika, lokhazikika la GH secretagogue receptor (GHSR1a), ndi mahomoni ambiri omwe amachokera m'mimba, omwe amachititsa kuti madzi asamadzike bwino chifukwa cha mphamvu zopanda mphamvu kuti ziwonetsetse kuti zimakhala zovuta kwambiri. . Kuchokera pharmacologically, Ser³-n-yotanoylated mawonekedwe a ghrelin ndi orexigenic ndipo amachepetsa kugwiritsa ntchito mphamvu ndi kugwiritsira ntchito mafuta monga gawo lapansi, kutitsogolera kulemera phindu ndi zochepa ndi aakulu aakulu administration (Zosintha Et al, 2006; Tschop Et al, 2000; Wortley Et al, 2005). Chifukwa chakuti leptin ndi ghrelin mowonjezereka zikuwonjezeka ndi kuchepa pa makoswe a chow / osakondedwa, kunenepa kwambiri ndi kusintha kwa zakudya kumayendetsedwa bwino ngakhale kukhala koyenera-bwino, malo otetezeka a homeostatic mpaka mahomoni onse (monga chakudya chomwe chimayambitsa kunenepa kwaumunthu), osati chifukwa cha kusemphana maganizo kumasulidwa.

Kunenepa kwaumunthu kwagwirizananso ndi kuchepa kwa mphamvu ya seramu GH, kuwonetsera kuchepa kwa moyo, kuchuluka kwa zigawo zachinsinsi, ndi kupanga tsiku ndi tsiku (Scacchi Et al, 1999). Makoswe a Chow / odyetsedwa omwe adasankhidwa amasonyezanso 47% kuchepetsa kutulutsa GH. Za kufunika kwa pathophysiologic, zomwe zimakhala ndi kuchepa kwa ma GH (mwachitsanzo, kukalamba, matenda a GH, ndi kunenepa kwambiri) zimakhala zoopsa za matenda a mtima (Gola Et al, 2005; Hoffman, 2005).

Mwachidule, makoswe omwe sali ndi mwayi wokhala ndi zakudya zapamwamba-sucrose, zomwe amakonda kwambiri zimagwiritsidwa ntchito popanga zakudya monga kudya ndi kuyerekezera zosiyana, zomwe zingakhale zovomerezeka pa zakudya, pa makoswe aakazi a Wistar. Ophunzirawa, okhwima-omwe amachititsa kuti anthu azikhala odyetserako zakudya ndi opioid-amadalira ndi dissociable nthawi ndi munthu wina ndi mzake. Kuchuluka kwa mlingo umodzi woterewu kunalepheretsa kusiyana kwakukulu komanso mofulumira ndipo pang'onopang'ono kunachepetsanso 'kubetcherana,' pafupifupi chakudya chokhazikika cha caloric. Makoswe okhala ndi chakudya chochepa cha shuga anawonetsa kuwonjezeka kwa nkhaŵa-monga khalidwe ndi maonekedwe a morphometric ndi hormonal a fetceral obesity. Zotsatirazi zimagwirizana ndi lingaliro lakuti kuperewera kwapadera kwa zakudya 'zoletsedwa' zosakanizidwa kungakhale ndi gawo lothandizira pa chitukuko cha kudya mowa kwambiri, zokonda chakudya, kunenepa kwambiri, ndi matenda okhudzidwa.

Pamwamba pa tsamba 

zolemba

Kufotokozera / Kusamvana kwa chidwi

Olembawo akulengeza kuti palibe zokangana.

Pamwamba pa tsamba 

Zothandizira

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