Zakudya Zowonjezera Zakudya Zowonjezera Zowonjezera Zowonjezera Sucrose Self-Administration Mu Young Rats (2013)

. Zolemba zolemba; ilipo mu PMC 2014 Feb 1.

Lofalitsidwa mu mawonekedwe omaliza omaliza monga:

Kudya. 2013 Feb; 61 (1): 19-29.

Idasindikizidwa pa intaneti 2012 Sep 27. do:  10.1016 / j.appet.2012.09.021

PMCID: PMC3538965

NIHMSID: NIHMS411020

Kudalirika

Tanena kale kuti chakudya chamtengo wapatali cha mafuta chimapangitsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda. Mu phunziro ili, tinayesa zolimbikitsa, matenda a m'mitsempha, komanso zowonongeka za zakudya zamtundu wa mafuta zamphongo zomwe zimasintha pofika msinkhu, pa masabata a 5-8. Tinawona kuti chakudya chambiri chokwera chinawonjezereka kuyankha kwa sucrose, yomwe idali yosasinthika ndi kusintha kwa thupi kapena kusintha kwa catecholamine neurotransmitter metabolites mu nucleus accumbens. Komabe, magulu a AGRP mRNA mu hypothalamus anali okwezeka kwambiri. Tasonyeza kuti kuwonjezereka kwa mphamvu za AGRP ndizitsitsimutso zimakhudzana ndi khalidwe lolimbikitsana, ndipo kuwonetsetsa kwakukulu kwa (AGRP) yachitatu (cerebroventricular) kulamulira kunachititsa kuti chiwerengero cha sucrose chiwonjezeke kwambiri. Izi zikuwonetsa kuti kufotokozera kwowonjezereka ndi ntchito za AGRP mu hypothalamus yamkati zimatha kuchepetsa kuyankha kwa sucrose chifukwa cha zakudya zapamwamba zowonjezera mafuta. Pomaliza, ife tinayimirira zofuna za sucrose polemba poyera ndi makoswe akuluakulu ndipo tinawona kuwonjezereka kwa sucrose mu makoswe otha msinkhu, zomwe zikugwirizana ndi zomwe zapitazo kuti nyama zinyama ndi anthu ali ndi chidwi chokoma, poyerekeza ndi akuluakulu. Pamodzi, maphunziro athu amasonyeza kuti zakudya zam'mbuyo zimathandiza kwambiri kuti zikhale zokoma pa nyama zinyamata.

Keywords: Chilimbikitso, chakudya cha mphotho, zakudya zamakono, achinyamata

Introduction

Tanena kale kuti kudya pang'ono kwa mafuta ochepa (31.8%) kudya kumabweretsa chikoka cha sucrose mu makoswe akuluakulu (). Zomwe zimayenderana ndi chilengedwe, zokhudzana ndi zakudya, komanso zofuna za zakudya zowonjezera zakhala zikuyamikiridwa zaka khumi zapitazo. Izi zawonjezera kufunikira kwa achinyamata, monga kunenepa kwa ana kwawonjezeka kwambiri zaka khumi zapitazi (). Kuwonjezeka kukonda kukoma kokoma kwatchulidwa pa zinyama zonse ziwiri ndi chiwerengero cha ana aumunthu (; ; ; ; )), ndipo ndizochititsa kuti chakudya chisawonongeke ndikupanga zakudya ndi zakumwa zogawanika ndi shuga wambiri, kwa ana. Komabe, zotsatira za zokhudzana ndi chilengedwe, monga zakudya zakumayambiriro, zomwe zimachititsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda zisamangidwe, sitinayesedwe bwinobwino.

Zomwe zilipo panopa zikusonyeza kuti 10-20% ya ana ndi anyamata ku US akuonedwa kuti ndi ovuta (). Kawirikawiri anthu a ku America amadya 336 kcal ya shuga wambiri tsiku lililonse (National Cancer Institute Applied Research Program). Pamene anthu akulekanitsidwa kukhala akuluakulu (zaka za 19 +) ndi chiwerengero cha ana (zaka 2-18), nambalayi ndi yapamwamba kwambiri kwa ana / achinyamata komanso kuchepa kwa akuluakulu. Kwa achinyamata, ambiri amathira shuga amachokera ku soda, zakumwa zakumwa, ndi zakumwa za masewera (National Cancer Institute Applied Research Program). Kukambirana kwakukulu kwambiri ndi kusanthula mchere kwawonetsa kuti kudya kofewa kumagwirizanitsa ndi kuwonjezeka kwa mphamvu yowonjezera mphamvu ndi thupi (). Achinyamata (14-18 wazaka) amadya shuga wowonjezera wokwanira 444 kcal tsiku lililonse, ndipo ana azaka zapakati pa 9 ndi 13 azaka zakumwa amadya shuga 381 kcal tsiku lililonse (National Cancer Institute Applied Research Program). Zakudya zowonjezerazi zitha kuchitika chifukwa chakukonda kwambiri kwa achinyamata poyerekeza ndi achikulire (; ; ; ). Kafukufuku wasonyeza kuti ana a zaka zapakati pa zaka za 9 ndi zaka za 15 amakonda kusankha njira zothetsera shuga pazikuluzikulu kusiyana ndi chitsanzo cha anthu akuluakulu.). Maphunziro a kutalika kwa nyengo akhala akuyesa zokonda za ana awa zaka khumi m'tsogolo mwa moyo, pomwe panthawi yomwe zakondwerero zawo zatsika ndipo sizinali zosiyana kwambiri ndi zomwe akulu amakonda.). Zofukufuku zawonetsanso zosankha zapamwamba za ana a sucrose poyerekeza ndi amayi awo (). Izi zikusonyeza kuti kukula kwa msinkhu wa shuga sikumayambitsidwa ndi majini, koma m'malo mwake kungasonyeze chonchi. Kafukufuku akuwonetsanso kuti chidwi cha sucrose chomwe chimakonda kwambiri makoswe ().

Mitundu yambiri ya CNS ndi zomangamanga ndizopulasitiki panthawi ya unyamata pakati pa anthu ndi makoswe, kuphatikizapo mesocorticolimbic system ndi ntchito ya dopaminergic mu nucleus accumbens, malo ofunikira kuyanjanitsa mphotho ndi zolinga (; ) (onani kwa kafukufuku waposachedwa). Zomwe zimagwira ntchito za kusintha kwa matendawa ndi zomwe zimachitika tsopano. Kafukufuku waposachedwapa kuchokera ku Bolaños ndi ogwira nawo ntchito, ndi ena, akhala akufufuza zotsatira zothandizidwa ndi dopamine kubwezeretsanso antagonist methylphendate (Ritalin) mu ndondomeko yotsitsimula, anyamata. Pali malipoti okhudza kusintha kwa matenda a ubongo ndi khalidwe la munthu wamkulu ngati ntchito ya mankhwala ochizira achinyamata ndi methylphenidate (; ; ; ). Ngakhale kuti zofukufukuzo siziri zogwirizana, mwinamwake chifukwa cha mitundu yosiyanasiyana ya zinyama zomwe anaziphunzira, palimodzi maphunzirowa akugogomezera kuti nthawi yaunyamata ikuwoneka ngati chitukuko cha kusintha kwa dopamine ntchito. Chakudya ndichilengedwe chothandizira kutulutsa dopamine kuchokera ku ventral tegmental area (VTA) kuyerekezera kwa nucleus accumbens, ndipo kudya moyenera kwa sucrose ndi makoswe kumabweretsa dopamine (). Timaganiza kuti chikoka cha sucrose chikugwirizana ndi kuwonjezeka kwa nucleus accumbens dopamine, ndipo kusintha kwa kayendedwe ka zowonongeka kwa zachilengedwe kungakhale kovuta kwambiri pa nthawi yachinyamata, nthawi yowonjezera pamakina.

Chifukwa chokonda kukoma kwa ana ndi makoswe, tinkaona kuti ndi zofunika kuti tizindikirenso zomwe zimayambitsa sucrose mu makoswe achinyamata. Mu zochitikazi, tafufuza momwe zotsatira za zakudya zowonjezera mafuta zimathandizira kuti sucrose mu makoswe pamene akukula kuchokera kumbuyo kwa kusamba panthawi ya kutha msinkhu. Pambuyo pake tinayesa kugwiritsira ntchito kayendedwe kake ka zitsamba ndi kasamalidwe ka HIV kuti tizindikire zamagetsi, mapuloteni, kapena kusintha kwa thupi. Poyerekeza ndi zomwe tazilemba mu makoswe akuluakulu, mafuta ochepa kwambiri (31.8%) amadya kwambiri poonjezera sucrose kudzilamulira. Tinayesedwanso ngati pali mankhwala opatsirana pambuyo pa zakudya pa sucrose zomwe zimakhudza makoswe ngati achikulire, zofanana ndi zomwe zimachitika pambuyo pake zomwe zimafotokozedwa ndi makhalidwe ena. Maphunziro athu amasonyeza kuti makoswe achionetsero amachititsa chidwi cha sucrose podyetsa zakudya zamtundu wapamwamba zomwe zingakhale zogwirizana ndi orexigenic, hypothalamic peptide AGRP; kuti zikuwoneka kuti palibe zotsatira zowonongeka kwa zakudya zoyambirira zowonongeka, kupita kumbuyo kwa anthu akuluakulu; komanso kuti khalidweli likuwonetseredwa ngakhale kuti makoswe amakhala ochizira kwambiri, ndipo asanakhale ovuta. Pomaliza, makoswe a peripubertal amachititsa chidwi cha sucrose poyerekeza ndi makoswe akuluakulu.

Zida ndi njira

Ophunzira

Amunawa anali amphongo a Albino ochokera ku Simonsen (Gilroy, CA). Makoswe ankasungidwa pa chow (Zakudya Zamakono Zakudya 5001, LabDiet) kapena zakudya zochepa kwambiri za mafuta (31.8%; Research Diets Inc) ad libitum. Zakudya zimayenderana ndi zonse zomwe zimapezeka m'magazi (58% kcal vs. 51% kcal mafuta ochepa ndi mafuta okwera, mwachitsanzo). Mafuta a mafuta ochepa ali ndi 6.23 gm% shuga opanda mafuta ndipo zakudya zamtundu wa mafuta ndi 29 gm% sucrose. Anasungidwa pa 12: 12 h kuwala-mdima ndi kuwala pa 6 AM. Pokhapokha ngati tasonyeza, makoswe analowetsedwa pa masabata a 3, nthawi yomweyo atasiya kusamba, ndipo adakonzedweratu kuti azitha kuchepa mpaka masabata a 5. Pa msinkhu uno, zakudya ndi / kapena khalidwe lophunzitsira ndi kuyezetsa zinayamba. Mapulogalamu enieni amalembedwa mwatsatanetsatane, ndipo mwachidule Gulu 1. Chifukwa makoswe amatha msinkhu ku 6th-7th sabata ya zaka, maphunziro a nthawi yaying'ono kuti aphunzire makoswe pamene akudutsa gawoli. Njira zonse zogwiritsidwa ntchito pa makoswe amatsatira malangizo a NIH othandizira zinyama, ndipo anavomerezedwa ndi Komiti Yogwirizira ndi Zogwiritsira Ntchito Komiti Yoyang'anira ndi Kupititsa patsogolo pa VA Puget Sound Health Care System.

Gulu 1  

Mapulogalamu Oyesera

Sucrose kudziyang'anira bwino

General Protocol. Ndondomeko zinakhazikitsidwa pa njira zathu zofalitsidwa (; ). Maphunziro onse ndi njira zoyesera zinkachitika pakati pa 0700 ndi 1200 hr. Kuyesera kunaphatikizapo magawo a 2-3: kuphunzitsa koyendetsera (FR) ndi chiwerengero chokwanira; kuchitidwa opaleshoni ndi kuchiritsidwa m'magulu otchulidwa (onani Gulu 1); ndi kupititsa patsogolo (PR) maphunziro pogwiritsa ntchito PR algorithm a Richardson ndi Roberts (). Pulogalamu ya PR imayenera 1, 2, 4, 6, 9, 12, 16, 20, 28, 36, 48, 63, 83, 110, 145, 191, 251, 331, 437, 575 ( ndi zina zotero) kuyimitsa mphoto kuti apindule mphotho yopereka gawo limodzi, ndipo ndiyeso lovuta kwambiri lolimbikitsa ndi mphotho (759). Makoswe adaphunzitsidwa kuti adzilamulire 999% sucrose (mphoto ya 999 ml) yoperekedwa mu dontho la madzi. Mabotolo ogwiritsira ntchito, omwe ankalamulidwa ndi dongosolo la Med Associates (Georgia, VT), anali ndi levers ziwiri, koma nkhumba imodzi yokha (yogwira ntchito yogwira ntchito, yotsegula) inayambitsa kulowetsedwa kwa mpope. Amagwiritsa ntchito chiwindi china (chosatetezeka, chotsamira pamoto) nawonso analembedwanso. Yankho la sucrose linaperekedwa mu dontho la madzi lovomerezeka kuti liperekedwe pamlomo (Med Associates). Maphunziro oyambirira ankachitika patsiku limodzi la ma HNUMX masiku amodzi (FR27: makina osindikizira onse ankalimbikitsidwanso), pokhapokha padzakhala mphoto ya 5 sucrose. Gawo lirilonse linayambika ndi kuyika kwa chiwindi chogwira ntchito ndi kuunikira kwa nyenyezi yoyera yomwe inatsalira pa gawo lonse. Phokoso la 0.5 (10 Hz, 1 dB pamwamba pa maziko) + kuwala (50 Kuwala koyera pamwamba pa chiwindi chogwira ntchito). Maphunziro a PR adayendetsedwa kwa 5 tsiku ndi tsiku kwa masiku khumi. Mapulogalamu a tsiku ndi tsiku anamatha pambuyo pa 2900 min opanda makina osindikizira atayankha, panthawi yomwe nyumbayo inatsekedwa ndipo chiwindi chogwira ntchito chinachotsedwa.

Zotsatira za AGRP pa sucrose self-administration

Monga momwe zotsatira zathu zinasonyezera kuwonjezeka kwa mawu a AGRP mRNA mu makoswe a pubertal amadyetsa zakudya zamakono, tinkafuna kutsimikizira kuti AGRP ingawonjezere sucrose kudzilamulira. Makoswe akale a 5-wk omwe anagwidwa ndi feteleza adatengedwa kudzera mu maphunziro a FR, kenako amalandira mankhwalawa mu chigawo chachitatu cha ubongo (ICV). Pambuyo pa sabata yowonongeka, kutsimikiziridwa kwa chikhazikitso ndi mayeso a angiotensin II akumwa mowa (onani ), ndi gawo limodzi la FR re-training, makoswe anayambitsidwa pa PR kudzilamulira bwino paradigm. Pambuyo pa PR Tsiku 1, makoswe anapatsidwa ntchito imodzi mwa magulu awiri omwe amatanthawuza kuti ntchito ya PR Day 1 siinali yosiyana pakati pa magulu awiri (galimoto ya CSF, aCSF, AGRP, 2 μl ya 0.01 nmol). Analandira jekeseni wa aCSF (n = 8) kapena AGRP (n = 7) pa masiku PR 2, 5, ndi 8. Chiwerengero cha chakudya cha tsiku ndi tsiku chinali chochuluka pa nthawi ya maphunziro a PR.

Zotsatira za msinkhu pa sucrose self-administration

Tinafananitsa khalidwe lodzikonda okha pakati pa makoswe ndi achinyamata, kudyetsa chow kapena zakudya za 31.8% mafuta. Makoswe anali ndi milungu iŵiri yokhala ndi mavitamini a VAPSHCS vivarium (3-5wk kapena 8-10 wk). Kenaka adalandira chakudya pa nthawi yonse yoyezetsa / maphunziro (4 wk). Motero, monga poyesa koyambirira, makoswe a pubertal anaphunziridwa pa 5-8 wk wa zaka. Achinyamata achikulire anaphunziridwa pa 10-13 wk wa zaka.

Thupi lokhazikika

Kuwoneka kwa thupi kunayesedwa pogwiritsira ntchito maginito oonera maginito (QMR []) kuti mudziwe zomwe zili m'madzi a makoswe, zomwe mafuta amthupi amawerengera. Zinyamazo zinkayikidwa muzitsulo zosakanizidwa, ndipo olembawo amalowetsedwa mu makina a QMR kuti ayambe kupima miniti ya 2, yomwe imachita miyendo itatu. Deta imasungidwa kumakompyuta ophatikizidwa (EchoMRI, Echo Medical Systems, Houston, TX) kuti azindikire mwamsanga madzi onse, mafuta, ndi oonda.

Kuyezetsa magazi kosakanikirana (IVGTT)

Mankhwala a IVGTTs amadziwika pogwiritsa ntchito makoswe okhala ndi maynulas a IV, omwe ankasala kudya usiku umodzi asanayambe kuphunzira, pogwiritsa ntchito njira . Zogwirizanitsa zida zogwirizanitsa zidaikidwa masabata awiri musanaphunzire, monga mwa njira zathu zakhazikika (). Zotsatira zapakati pazomwe zinayambira pa t-10 min (0.5 ml pofuna kutsimikiza kwa insulini ndi shuga, nthawi zonse) ndi t0 min. Makoswe analandira kulowetsedwa kwa 1 gm shuga / 2ml / kg pa 15-20 masekondi pambuyo pa 0.5 ml ya saline. Zotsatira za magazi zinatengedwa ku 5, 15, 30, 60, 90, ndi 120 min. Chifukwa chotsegula catheter panthawiyi (potero, sitingathe kupeza zitsanzo za magazi), n 'nthiti ya data yoyamba / IVGTT yomwe ilipo ndi 7-8 ya makoswe odyetsedwa ndi 8 kwa makoswe omwe amadyetsa 31.8% zakudya za mafuta (Gulu 3). Plasma insulin inatsimikiziridwa kugwiritsa ntchito Linco makulitsidwe a RIA makina (# RI-13K ndi SRI-13K, Linco) ndi shuga ya plasma inadziwika pa YSI Glucose Analyzer). Malo omwe ali pansi pa mphambu (AUC) poyankhidwa kuchokera pazowonjezera anawerengedwa pa 5 min ndi 120 min. Chiwerengero cha HOMA chinkawerengedwa ngati kusala (shuga [mM] × insulini [U / L]) / 22.5 ndipo inawerengedwa pogwiritsa ntchito zowonongeka zowonongeka kwa insulini ndi shuga.

Gulu 3  

Zida Zamatsenga1

Kusala zakudya zamagetsi

Makoswe Oyesera 1 anali kusala kudya usiku umodzi usanafike ku Euthanasia, masiku angapo pambuyo pa kutha kwa IVGTT. Makoswe anali otetezeka kwambiri ndi isoflurane inhalation ndi exsanguinated. Ubongo unachotsedwa mofulumira ndipo usungunuka mu nayitrogeni yamadzi kuti ayerenge za hypothalamic peptide mRNA ndi nucleus accumbens catecholamines. Plasma yamtundu kapena seramu ankagwiritsidwa ntchito poyerekeza ndi kusala kwa insulini, shuga, leptin, ndi triglycerides. Pogwiritsa ntchito triglycerides, Pulogalamu ya Scientific Triglyceride GPO # T7531-400 (Fisher # 23-666-418) ndi mfundo KIT # 7531-STD (Fisher # 23-666-422) zinagwiritsidwa ntchito, ndipo 3 μl ya seramu inayesedwa mobwerezabwereza. Leptin ya plasma inayesedwa ndi Millipore Linco RIA Kit # RL 83K.

Catecholamine HPLC Njira []

Makoswe amathandizidwa ndi isoflurane anesthesia, ndipo ubongo unachotsedwa mofulumira, wachisanu, ndi kusungidwa pa -80 ° C. Nkhono zazing'ono zamkati za nucleus accumbens (NAcc) zinali zosiyana ndi nyama iliyonse. Ngakhale kuti adasamalidwa kwambiri kuti zisokonezeke ndi zigawo za ubongo, pafupi ndi chikhalidwe ndi kukula kwa tizilomboti tomwe sitinalole kuti tisiyanitse zigawo (ie NAcc core vs. shell) mkati mwa NAcc. Kufufuza kwapamwamba kake (chromatography) (HPLC), njira yothetsera antioxidant (0.4 N perchlorate, 1.343 mM ethylenediaminetetraacetic asidi (EDTA) ndi 0.526 mM sodium metabisulfite inawonjezeredwa ku zitsanzo zomwe zatsatiridwa ndi kugwiritsiridwa ntchito kwa homogenizer (ultrasound); Gainesville, VA (A / v) a mapuloteni (Pierce BCA Protein Reagent Kit, Rockford, IL). Kupuma kwasana kunapangidwa pa 2 g kwa 14,000 min mu firiji centrifuge. Wopambana kwambiri anali kusungira HPLC.

Zitsanzo zinasiyanitsidwa pamtundu wa Microsorb MV C-18 (5 Am, 4.6_250 mm, Varian; Walnut Creek, CA) ndipo nthawi yomweyo anayezetsa DA, 3,4-dihydroxyphenylacetic acid (DOPAC) ndi homovanillic acid (HVA), zonsezi ndi zizindikiro za dopamine degradation, 5-HT ndi 5-HIAA. Mankhwalawa anagwiritsidwa ntchito pogwiritsa ntchito njira ya 12 yomwe imagwiritsidwa ntchito padera (CoulArray 5200, ESA; Chelmsford, MA) yogwirizana ndi madzi a 2695 Solvent Delivery System (madzi, Milford, MA) pansi pazifukwa izi: kuthamanga kwa 1 ml / min; zokhudzana ndi zizindikiro za 50, 175, 350, 400 ndi 525 mV, ndi; Kutsuka kwa 650 mV. Gawo la mafoni linali ndi 10% methanol yothetsera H2O 21 g / l (0.1 M) citric acid, 10.65g / l (0.075 M) Na2HPO4, 176 mg / l (0.8 M) heptanesulfonic acid ndi 36 mg / l (0.097 mM) EDTA pH ya 4.1. Zitsanzo zosadziwika zinali zotsatiridwa motsutsana ndi 6-mfundo yomwe ili yoyenera pambali ndi R2 ya 0.97. Zotsatira zowonongeka kwazitsulo zidalowa mkati ndi kuthamanga kulikonse kuti zitsimikizire HPLC calibration.

Orexigenic peptides mRNA qPCR

Tinayesera kufotokoza za peptide hypothalamic zomwe zimalimbikitsa kudyetsa ndikukhala ndi zolimbikitsa ndi zolimbitsa khalidwe (): neuropeptide Y (NPY [ ; ; ]); peptide yokhudzana ndi agasi (AGRP [; ; ; ; ; ; ; ; ]); ndi orexin (; ). Makoswe adalimbikitsidwa ndi isoflurane anesthesia, ndipo ubongo udachotsedwa mwachangu, kuzizira ndikusungidwa pa -80 ° C mpaka kukonza. Hypothalamus yapakatikati komanso yotsatira idasankhidwa ngati chidutswa chimodzi pogwiritsa ntchito ndege yozizira ya AHP-1200CPV (Thermoelectric Cooling America, Chicago, Il) yomwe imasungabe kutentha kwa 12 ° C nthawi yonseyi. RNA yonse yochokera kumatenda opangidwa ndi ma microdissected idadzipatula ndi Trizol reagent (Invitrogen, Carlsbad, CA) ndikuyeretsanso pogwiritsa ntchito RNeasy Mini Kit (Qiagen, Valencia, CA) malinga ndi malangizo a wopanga. RNA yonse idathandizidwa kuti ichotse kuipitsidwa kwa genomic DNA pogwiritsa ntchito RNase yaulere DNase (Promega, Madison, WI), ndipo idakonzedwa pogwiritsa ntchito NanoVue spectrophotometer (GE Healthcare, Cambridge, UK). Makhalidwe a RNA adatsimikizika ndi standard agarose gel electrophoresis. Complementary DNA (cDNA) idasinthidwanso (RT) kuchokera ku 1-2 μg ya RNA yathunthu posakaniza ma hexamers osakanikirana ndi oligo DT oyambira pogwiritsa ntchito iScript cDNA Synthesis Kit (Bio-Rad Laboratories, Inc., Hercules, CA). Zomwe sizinatchulidwenso (palibe RT) zomwe zidakonzedwanso kuchokera pachitsanzo chilichonse kuti zitha kuwonongera za DNA. Maulamuliro a cDNA ndi no-RT adasinthidwa, ndipo 5-10 ng ya template cDNA kuchokera pachitsanzo chilichonse idagwiritsidwa ntchito kuyerekezera mRNA kufotokozera kwamtundu wosankhidwa ndi PCR yeniyeni yogwiritsa ntchito MyIQ Real-Time PCR Detection System (Bio-Rad, Hercules Kuyesa kopitilira muyeso pamayeso aliwonse kunayendetsedwa pama mbale oyenera a iCycler 96, osagwiritsa ntchito ma template (NTC) kuti azindikire kuipitsidwa komwe kungachitike, mu 20 μl reaction volumes okhala ndi 10 μl 2 × iQ Sybr Green Supermix (Bio- Rad, Hercules, CA), 2 μl a 0.2-0.5 μM pachimake chilichonse, 3 μl madzi a DEPC, ndi 5 μl ya template. Zotsatira zonse za qPCR zidaphatikizapo kusungunuka kosungunuka kwa melt kuti zitsimikizire kulondola kwa siginolo. Chiwonetsero chofananira cha jini iliyonse yosangalatsa chinawerengedwa ndikuwonjezera pamzere wokhazikika womwe umayendetsedwa pa mbale iliyonse ndikuchokera m'miyeso yofananira ya cDNA yolembedwera, ndikuzolowereka kutanthauzira kwa majini ofananirako (acidic ribosomal phosphoprotein 36B4 yokhudzana ndi majini minofu ya hypothalamic, ndi mapuloteni a mitochondrial ribosomal L32 kuti awonetseke mu nucleus accumbens). Zotsatira zotsatirazi (IDT, San Diego, CA) zinagwiritsidwa ntchito kukulitsa makoswe a prero-orexin, NPY, ndi AGRP: Prepro-orexin, Forward: 5'-TTCCTTCTACAAAGGTTCCCT-3 ', 5'-GCAACAGTTCGTAGAGACGGAG-3'; NPY: Pitani, 5- TACTCCGCTCTGCGACACTACATC-3 '; Bweretsani: 5'-CACATGGAAGGGTCTTCAAGCC-3 '; AGRP, Patsogolo: 5'-GCAGAAGGCAGAAGCTTTGGC-3 '; Bweretsani: 5'-CCCAAGCAGGACTCGTGCAG-3 '.

cFos Immunocytochemistry (ICC) ndi Kuwonjezera

Fluorescence ICC inagwiritsidwa ntchito pozindikiritsa matupi a fos-positive ndi AGRP-neuronal cells mu medi medial hypothalamus, malingana ndi njira zathu zovomerezeka (). Patsiku lomaliza (PR Day 10), makoswe adayikidwa muzipinda zawo zodziyang'anira monga mwachizolowezi, kwa 90 min. Pambuyo pa gawo lomaliza la 90 min, makoswe anali atatenthedwa kwambiri ndi isoflurane inhalation ndipo anapakidwa ndi 0.9% NaCl yotsatira ndi yankho lozizira la 4% paraformaldehyde. Nthawi ya anesthetic ndi euthanasia idakhazikitsidwa pa nthawi yodziwika bwino ya cFos protein pa 90-120 min-post chochitika. Chifukwa chake kufotokozera kwa cFos kumawonetsa kuyambitsidwa kwa CNS koyambirira kwa ntchitoyo, m'malo mokhala zotsatira za nyama zomwe zikugwira ntchitoyi. Ubongo unachotsedwa ndikukhazikitsidwa mu paraformaldehyde masiku angapo, kenako ndikuikidwa mu 20% sucrose-PBS, kenako 30% sucrose-PBS yankho. Ubongo udagawidwa pa cryostat (Leica CM 3050S cryostat) ya immunohistochemistry. Tidagwiritsa ntchito njira zathu zokhazikitsira kuchuluka kwa mapuloteni a cFos osagwira ntchito m'magawo aubongo (). 12 μm zonse-zigawo za ubongo zotsekedwa zinatsukidwa katatu mu saline yotchedwa phosphate (PBS, OXOID, Hampshire, England). Zigawo zinatsukidwa kwa 20 min ndi 100% ethanol / DI madzi (50%, v / v) otsatiridwa ndi kutsuka kwa PBS, kenaka kutsekedwa kwa ola la 1 kutentha kwapakati pa PBS yomwe ili ndi 5% ya mbuzi yamphongo kapena bulu wamba. Zigawozo zimatsukidwa nthawi zambiri mu PBS ndipo zimagwiritsidwa usiku umodzi pa 4 ° C m'magulu oyamba a antibody omwe amapanga PBS. Zigawo zinatsukidwa katatu mu PBS ndiyeno zimayikidwa mu mdima kutentha kwapachilombo kachilombo kamene kamapangidwa mu PBS kwa ola la 1. Zigawozo zinatsukidwa kachiwiri mu PBS, ndipo zinakwera ndipo zimaphimbidwa mu Vectashield yolimba kwambiri yosungira miyendo (Vector; Burlingame, CA). Zithunzi zamagetsi za zigawo zinapezedwa pogwiritsa ntchito microscope ya Nikon Eclipse E-800 fluorescence yomwe imagwirizanitsidwa ndi kamera kamakono kamakono kamene kamagwiritsa ntchito NIS Elements (Nikon).

Malingana ndi kafukufuku wa PCR powonetsa mawonjezereka a AGRP mRNA, tinayang'ana ku madera a m'madera ozungulira, makamaka phokoso lachitsulo komanso phokoso la ARC). Mapu a XMUMX omwe amagwiriridwa ndi Atlas anawerengedwa chifukwa cha cFos kufotokoza komanso kuchuluka kwa magawo ndi zigawo, zochokera pa mabala . Kwa kuchulukitsa (pa 40 × kukuza), madera ozungulira atlas anasankhidwa. Pulogalamu ya NIS Elements (Nikon) idagwiritsidwa ntchito kuti igwire chithunzi cha malo omwe mukufuna. Malo omwe adasankhidwa kuti awerenge ndi kulemba kuti ziwerengero zabwino za selo zakhazikitsidwe zinakhazikitsidwa. Dera lomwelo ndi malo omwe amachitikirapo analigwiritsidwa ntchito pa magawo ochokera m'magulu oyesera, ndipo kuwerengera mapulogalamu abwino (kuchuluka kwa maselo) kunkachitika panthawi imodzimodziyo kwa magulu onse oyesera, pofuna kuteteza kusintha pakati pa magawo kumbuyo. Kuwerengera kwa chiwerengero, chiwerengerocho chinatengedwa kuchokera kumtunda wokha pokhapokha ngati zigawo zofanana kapena zodzaza kudutsa m'deralo zilipo; Dera ladera lina silinatengedwe ndi makoswe ngati panalibe chiwonetsero chosakwanira cha dzikoli.

Kuphatikiza pa kuchuluka kwa cFos, kuchuluka kwa ma immunohistochemistry a cFos ndi AGRP kunachitika. Chifukwa sitinkafuna kusokoneza machitidwe anyamazo, sanapatsidwe chithandizo ndi colchicine kuti athandizire kuwona kwa AGRP. Chifukwa chake kuwonera ma neuron okhala ndi AGRP atha kuchepetsedwa. Njira zowonera za AGRP zinali zofanana ndi kuyesa kwa cFos-immunoreacaction palokha, kupatula kuti zigawozo zidatsekedwa kwa ola limodzi kutentha kwapakati mu PBS-5% serum ya bulu. Kenako, chisakanizo cha fos-Ab ndi ma antibodies oyambira a AGRP adagwiritsidwa ntchito pophatikizira usiku umodzi pa 4 ° C; momwemonso ma antibodies achiwiri onse anali mumayankho omwewo ndipo adakhala kwa ola limodzi mumdima kutentha kwanyumba. Kuyesa koyamba koyeserera kunkachitidwa kuti athe kudziwa kusungunuka koyenera kwa ma antibodies oyambilira. Ma antibodies oyambilira omwe amagwiritsidwa ntchito anali akalulu odana ndi cFos (1: 500) (sc-52) ndi anti-AGRP (1: 100) (18634) (Santa Cruz Biotechnology, Inc., Santa Cruz, CA). Ma antibodies achiwiri omwe amagwiritsidwa ntchito anali a cy3-conjugated bulu odana ndi kalulu (Jackson Immunoresearch; West Grove, PA), ndi Alexa fluor 488 bulu wotsutsa mbuzi IgG (Molecular Probes, Eugene, OR); ma antibodies onse achiwiri adasungunuka 1: 500.

Kusanthula kusanthula

Zambiri zamagulu zimawonetsedwa ngati njira ± zolakwika zenizeni za tanthauzo (SEM) pamalemba, Matebulo, ndi Ziwerengero. Kufunika kumatanthauzidwa ngati p ≤ 0.05. Ziwerengero kuyerekezera kumapangidwa pakati pamagulu oyeserera, monga afotokozedwera pansi pa "Zotsatira" pogwiritsa ntchito mayeso osaphunzitsidwa a Ophunzira (mwachitsanzo, zakudya, zaka, kapena kuyerekezera chithandizo). 'Kukhazikika' kwa deta kumatanthauzidwa momwe imagwiritsidwira ntchito.

Results

Zotsatira za zakudya zochepa kwambiri za mafuta pa peri-pubertal zifukwa za sucrose

Amphaka adadyetsa chakudya cha 31.8% panthawi ya 5-8, pomwe panthawi yodzilamulira, anali ndi zifukwa zomveka zowonjezera sucrose, poyerekeza ndi makoswe odyetsedwa. Monga momwe taonera Chithunzi 1a, panalibe kusiyana pakati pa mapulogalamu oyambirira a FR (makina osindikizira a FRDays 1-10 omwe amawagwira ntchito, 38 ± 5 vs. XUMUM ± 39 kwa chow vs. 2% chakudya cha zakudya, motsatira). Komabe, pamene makoswe amasinthidwa ku ntchito yowonjezereka ya PR, panali kuwonjezeka kwakukulu kwa makina osindikizira a lever, ndipo nambala ya madalitso a sucrose atengedwa, koma osati muutali wonse wa gawo (Chithunzi 1b). Panalibenso zotsatira za mankhwala osapatsirana omwe amalephera kugwira ntchito. Pamene makoswe anadyetsedwa zakudya zamtundu wa mafuta m'kati mwa 5-8 koma kenako anabwerera ku chakudya chaching'ono chomwe chinaperekedwa kudzera mu FR ndi PR pa masabata a 9-12, panali chizoloŵezi koma palibe kusiyana kwakukulu m'makina osindikizira a lever. Choncho, zikuwoneka kuti palibe khalidwe lopangidwira labwino la zakudya zamtundu wa mafuta ochepa kwambiri zomwe zimadya nthawi ya pub-time. Deta ya PR parameter ya othandizira awa ikufotokozedwa mwachidule Gulu 2. Kuti tiyambe kufotokoza njira zowonjezeretsera zakudya zowonjezera zakudya za sucrose, tinapanga miyeso yambiri yotsitsimutsa ndi ya CNS.

Chithunzi 1Chithunzi 1  

PR yogwira ntchito yopempha sucrose mphoto imakula mu makoswe a peripubertal amadya chakudya cha 31.8% cha mafuta (n = 8). 1a. Pakati pa magawo a FR, panalibe zotsatira za zakudya, koma zotsatira zodyera zimawonekera pamene makoswe amasinthidwa ku PR. 1b. Deta ndizo ...
Gulu 2  

Zotsatira za Peri-Pubertal High Fat Zakudya Zakudya Zolimbitsa Thupi Zochita za Sucrose

Zotsatira za zakudya zamtengo wapatali zowonjezera mafuta pamagetsi

Pambuyo pa kumaliza kwa kuyesa khalidwe, thupi la mafuta limapangidwira pa makoswe omwe anali ndi zakudya zowonongeka ndi machitidwe a makhalidwe pa nthawi ya 5-8. Makoswe adalandira zilonda zam'mimba zowonongeka (IVGTTs). Pambuyo pake, madzi opangira magazi ndi seramu amatha kupeza zina zowonjezereka. Monga momwe taonera Gulu 3, panalibe kusiyana kwa thupi, kulemera kwa thupi, kusala kudya kwa insulini kapena shuga, kutsekemera kwa insulini (kuwerengera kwa HOMA) kapena mayankho a IVGTT, pakati pa makoswe odyetsedwa ndi mafuta odyetsa. Kutsalira kwa leptin ndi triglyceride sizinali zosiyana pakati pa magulu awiriwa. Choncho, ngakhale kuti mankhwalawa anali ndi zotsatira zowonjezereka pachitsime cha sucrose, amasonyeza khalidwe labwino pa makoswe odyetsa mafuta omwe ali ochepa kwambiri.

Zotsatira za zakudya zolimbitsa thupi kwambiri pa CNS homeostatic ndi mphotho yamagetsi

Kuphatikiza pa miyeso yamagetsi, ubongo wochokera ku gulu lomwe linali ndi zakudya zolimbitsa thupi komanso khalidwe labwino mu masabata 5-8 anayesedwa chifukwa cha nucleus accumbens mbiri ya amine (n = 4 pa gulu la zakudya) kapena mRNA ya peptides orexigenic orexigenic. Monga momwe taonera Gulu 4, panalibe zotsatira zabwino za zakudya zamtengo wapatali pa dopamine, norepinephrine, kapena serotonin metabolites mu nucleus accumbens, malo opambana a mphoto ndi ntchito yogwira mtima (; ) momwe machitidwe amtundu wa neurotransmitter amathandizira. Mkati mwa zotulutsa za hypothalamic, milingo ya mRNA yama peptide orexigenic, NPY, AGRP, ndi orexin adayesedwa. Chikhalidwe champhamvu koma chosafunikira pakuwonjezeka kwa AGRP m'makoswe onenepa kwambiri adawonedwa mgulu ili (n = 8 pachakudya chilichonse); Chifukwa chake tidabwereza paradigm yophunzitsira yazakudya pagulu lowonjezera ndikuyeza NPY, AGRP, ndi orexin mRNA mu hypothalamus. M'magulu ophatikizana, tawona kuwonjezeka kwakukulu (p <0.05) kwa AGRP mRNA mu makoswe omwe amadyetsa zakudya zamafuta ambiri motsutsana ndi chow chowongolera (Chithunzi 2), koma palibe kusintha kwakukulu mu NPY kapena orexin mawu. Pofuna kudziwa momwe mungagwiritsire ntchito mgwirizano pakati pa AGRP ndi khalidwe lodzilamulira, tinayesa kuchuluka kwa cFos ndi AGRP osatetezeka m'thupi mwa mediobasal hypothalamus. Magulu a makoswe adadyetsedwa chakudya cha chow kapena 31.8% mafuta; ena adatengedwa kupyolera mwawekha (masabata 5-8) ndipo ena adasankhidwa monga machitidwe oyendetsa khalidwe. Chithunzi 3a imasonyeza chitsanzo chokhazikika pakati pa cFos ndi AGRP mu nucleus neuron. Monga mwachidule Gulu 5, kutsegulira kwa AGRP neurons (kufotokozera kwa cFos-ICC ndi AGRP-ICC mkati mwa maselo omwewo) kunkagwirizana ndi ntchito yodzilamulira. Izi zikuwonetsedwa Chithunzi 3b, pamene chiwerengero cha nthenda (cFos-positive) chonyezimira chikuwonetsedwa ngati neuronal cell count, kapena peresenti ya zithokomiro zonse za AGRP: pali kusintha kwakukulu kwa AGRP neurons mu makoswe odziyang'anira sucrose, vs. , m'magulu odyera pamodzi. Kulingalira kwa mankhwala m'kati mwa chiwerengero cha ziwalo za AGRP zowonjezeredwa mu gulu loyang'anira makampani potsatira kuwongolera machitidwe akuwonetsa chizoloŵezi chomwe sichinafikire chiwerengero chofunikira (chow, p = .078; 31.8% mafuta zakudya, p = .073) . Chofunika kwambiri, sikuti izi zimagwirizanitsa ntchito ya AGRP yokhala ndi khalidwe lodzilamulira, koma chifukwa cha nthawi ya kuchuluka kwa cFos (maminiti 90 pambuyo pa makoswe atayikidwa m'chipinda chawo choyang'anira), cFos kufotokoza zimasonyeza ntchito za ma ARVs mu AGRP kuyembekezera, kapena poyambira, ntchito yodzilamulira. Panali njira yosafunika yowonjezereka ya nthenda zonse za AGRP mu gulu lodzilamulira (vs. kutsogolera kulamulira, p = 0.16). Mu makoswe, komwe kukakamizika kwa nsomba kunkafanana pakati pa magulu odyera, nambala ya AGRP-neurons inalinso yofanana. Panalibenso zotsatira za mankhwala okhawo pa nthenda zambiri za AGRP-neurons mu makoswe oletsa khalidwe.

Chithunzi 2  

Zotsatira za mafuta a 31.8% pamafuta apakati a hypothalamic peptide mRNA. Zambiri zimasinthidwa kukhala makoswe odyetsedwa mafuta kwambiri (n = 17) motsutsana ndi owongolera chow (n = 16). AGRP mRNA yakwezeka kwambiri (p <0.05).
Chithunzi 3Chithunzi 3  

Kugwiritsa ntchito mankhwala a AGRP kumayambiriro kwa sucrose kudzilamulira. 3a. Kugwirizanitsa ma CFos ndi AGRP pakukweza nucleus neuron, kukula kwa 60x. 3b. Chiwerengero cha zizindikiro zosavomerezeka (cFos-immunopositive) za AGRP-immunopositive neurons mu mediobasal hypothalamus ...
Gulu 4  

Nucleus Accumbens Metabolites Amine
Gulu 5  

Agrp Neuron Activation: Zakudya ndi Khalidwe Labwino

Zotsatira za bungwe la AGRP pa sucrose zolinga

Kutanthauzira kwathu kwa kupeza izi ndikutanthauzira kwa AGRP mu makoswe a pubertal ndi njira yofunikira yomwe imapangitsa kuti sachesise ikhale yoyendetsa makoswe a mafuta odyetsa. Kuti atsimikizire kuti mphamvu ya AGRP ikuthandizira kuonjezera chikoka cha sucrose, AGRP imayendetsedwa kudzera mu katemera wachitatu kuti ayambe kudyetsedwa ndi makoswe panthawi ya PR khalidwe la khalidwe. Dongosolo la mlingo wa AGRP linali gawo lochepa lokha la chakudya cha chow mkati mwa masabata awiri a PR paradigm, koma chinawonjezeka kwambiri kuwonjezera sucrose kudzilamulira, monga momwe tawonetsera mu Chithunzi 4. (Zindikirani kuti mphotho iliyonse ya sucrose ili ndi caloriki yokhudzana ndi 0.1 kcal, choncho sucrose kudziyang'anira ntchitoyo imapatsa makilogalamu osayenerera kuti azidya tsiku ndi tsiku.) Gulu 6 imasonyeza deta yoyendetsa padera pazithunzi za PR 9-day, ndi AGRP kapena aCSF yomwe inayikidwa ICV pa Tsiku 2, 5, ndi 8. Mu makoswe a AGRP, chiwerengero cha makina ogwira ntchito mwatsamba chinawonjezeka kwambiri patsiku la PR Days 2-10 (p = 0.03), ndi masiku osapanga (p = 0.048) ndi njira yoonjezera masiku osakaniza. Kuwonjezera pa nthawi, Stop Time (yomwe imawonetsera nthawi yonse yomwe inagwira ntchito yodzilamulira) yowonjezera kwambiri pa masiku osapanga (p = 0.02) ndi njira zowonjezera, ndi masiku operekera jekeseni. Chiwerengero cha madalitso a sucrose chinawonjezeka ponseponse mu PR Days 2-10 (p = 0.03). Panalibe zotsatirapo za mankhwala a AGRP pa kupuma kosalekeza koyerekeza, poyerekeza ndi machitidwe a treatments aCSF, kapena masiku opangira jekeseni ndi osapsa. Zotsatira zimathandizira kutanthauzira za zotsatira za AGRP kuti liwonjezere sucrose kudzilamulira: makoswe amathandizidwa kwambiri pa lever yopindulitsa, amalandira mphoto zambiri, ndipo amathera nthawi yowonjezera kugwira ntchitoyo.

Chithunzi 4  

AGRP yachitatu (ICV) (0.01 nmol) imapangitsa kuti munthu azidziyesa yekha m'dongosolo la PR, koma alibe mphamvu pa chakudya cha tsiku ndi tsiku pa nthawi yophunzira (PR Days 2-10, ndi jekeseni pa Days 2, 5, ndi 8) . AGRP (n = 9) deta ikufotokozedwa ...
Gulu 6  

Zotsatira za ICV AGRP vs. aCSF pa Zotsatira za Kupititsa patsogolo kwa Sucrose

Zotsatira za gawo la moyo pa zokonda ndi zolimbikitsa za sucrose

Poyesera komaliza, tinayesa ngati zolinga za sucrose zimasiyana pakati pa makoswe akuluakulu. Poyamba, makoswe akale a 5-ndi 10-wk anapatsidwa mayeso a sucrose omwe angasankhe njira zothetsera mavuto kuchokera ku 0 mpaka 20% sucrose, asanayambe kuyesa kuyesa ndi kuyesa. Monga momwe taonera Chithunzi 5a, ndipo zogwirizana ndi zofukufuku zomwe zalembedwa m'mabukuwa, makoswe am'mbuyo amaoneka ngati akufuna makoswe abwino kuposa makoswe akuluakulu: makoswe ambiri omwe asanatuluke pakamwa amakhala ndi chiwopsezo chachikulu cha 20% sucrose solution, pamene makoswe akuluakulu amasonyeza kuti ya 15% sucrose. Pambuyo pake, magulu onse a zaka zambiri adagawanika pakati pa rat chow ndi zakudya zamtengo wapatali panthawi yophunzitsira ndi kuyesa. Panali kuchuluka kochepa koma kodabwitsa kwambiri kuwonjezeka kwa makina osindikizira a lever ndi peri-pubertal vs. makoswe akulu (45 ± 3 vs. XUMUMI ± 37, p = 2) yowerengedwa kudutsa magawo a FR, popanda kusiyana kwa chiwerengero cha perekani mphoto kapena chiwerengero cha makina osokoneza chiwindi. Monga momwe taonera Chithunzi 5b, panali chiwopsezo chachikulu cha msinkhu wa zaka, kudutsa magawo a PR, ndipo kuwonjezeka kwakukulu kwa chiwindi kumaphatikizira pa pubertal (n = 15) vs. makoswe akuluakulu (n = 14) (njira ya 2 ANOVA, PRDay × zaka; zotsatira za zaka, p = 0.017, palibe zotsatira zodziimira za PRDay, palibe kugwirizana kwakukulu). Tthere anali chizoloŵezi chachikulu cha msinkhu wa zakudya zapamwamba zowonjezera mafuta koma izi sizinafike powerengera chiwerengero (p = .13). Gulu 7 amalembetsa mndandanda wa machitidwe a PR: Kuwonjezera pa makina osindikizira ogwira ntchito, mapiritsi ena amatha kulandira mphotho yambiri, ndipo amasonyeza njira yowonjezera Time Stop. Kuwonjezera apo, makoswe a peri-pubertal anali ndi kuwonjezereka kochepa koma kwakukulu kwa makina osakanikirana (ie, osapindulitsa) levisi, ngakhale kuti makoswe akuluakulu ndi akuluakulu, ngakhale kuti makoswe akuluakulu amatha, chiwerengero cha makina osakanikirana anali pafupifupi 10% ya nambala za makina opangira chiwindi. Zotsatira izi zimasonyeza kuti makoswe a peri-pubertal amakonda ndipo amayesetsa kufunafuna chakudya chokoma, ndipo zotsatira zake zikhoza kukulirakulira ndi maziko a zakudya zamtundu wapamwamba.

Chithunzi 5Chithunzi 5  

Nthongo zazing'ono zakhala zowonjezera zotsitsimula sucrose poyerekeza ndi makoswe akuluakulu. 5a. Mayeso okondedwa a asprose kwa achinyamata (peri-pubertal, n = 15) ndi makoswe akulu (n = 14). Makoswe anali ndi 30 min kumwa madzi osiyanasiyana (0-20% sucrose). ...
Gulu 7  

Zotsatira za msinkhu pa Kupititsa patsogolo Zowonjezera Kuchitaa kwa Sucrose

Kukambirana

Chowunikira chachikulu cha phunziroli ndi chakuti zakudya zamtengo wapatali zowonongeka pamapeto pa nthawi ya pubertal (kale, nthawi, ndi pambuyo pa msinkhu wa kutha msinkhu) kwambiri kuwonjezereka kwa zotsatira za sucrose. Izi zikugwirizana ndi zomwe takhala tikuziwona, zofanana, zomwe zimachitika pa makoswe akuluakulu (). M'nyamazi, komanso m'zinthu zowonjezera zakale ndi zothandizira mankhwala, tinatsimikiza kupyolera muzitsulo zamagetsi kuti makoswe sanali olemera kwambiri kapena anali ochepa kwambiri ndipo sanali atapukira mosavuta. Sitikudziwa kuti makoswewo anali ndi CNS-kukana kuteteza zochita za insulini kapena leptin, komabe: mahomoni onsewa amapangitsa kuti mphotho ya CNS yopezeka pamtunda (; ; ).

Pakati pa makoswe, tinayesa amine neurotransmitters ndi metabolites ofanana mu nucleus accumbens, yomwe imalandira ndalama zambiri za dopaminergic kuchokera ku midbrain, ndipo imatengedwa kuti ndipadera ndi yapakatikati ya CNS sitepe yothetsera mphotho ndi khalidwe lolimbikitsa (; ). Sitinasinthe kusinthika kapena kulinganirana kwa mavitabititseni awa omwe amasonyeza kuti kusinthika kwa mankhwala kapena kusintha kwa serotonergic mkati mwa nucleus accumbens si chinthu choyambirira kapena chachikulu cha CNS chomwe chimayambitsa kuchulukitsidwa kwa asprose. Izi zikugwirizana ndi lipoti la posachedwapa , amene anawonetsa makoswe akuluakulu kuti ICV AGRP iwonjezere chiwerengero cha dopamine m'kati mwa mapiritsi osakanikirana koma osati nucleus accumbens. Kuwonjezera apo, sitinaone kuti zotsatira za zakudya zimakhala zotani pamene zimayesedwa pa makoswe pamapeto pomwe atha msinkhu, monga achikulire. Izi zikusiyana ndi zomwe apeza kuchokera ku Bolaños ndi ena, pazochitika zonse zokhudzana ndi khalidwe ndi matenda, mu makoswe akulu omwe amachitira ndi methylphenidate (; ; ; ). Izi zikutheka chifukwa cha kulumikizidwa mwachindunji kwa dopaminergic neurons ndi methylphenidate, komanso kungakhale nthawi yogwiritsira ntchito zakudya komanso nthawi ya kuyesedwa kwa nyama. Pomaliza, mwina sitinayambe kuona zotsatira za carryover, chifukwa mu phunziro lino, malo oyamba kudya zakudya amaoneka ngati hypothalamus.

Phunziro ili, maumboni atatu amathandiza kwambiri kuti agrop hypothalamic neuropeptide yapitirize kuwonjezereka mwazidziwitso za mankhwala a sucrose pa makoswe odyetsa zakudya. Choyamba, tawona kuwonjezeka kwa mawu a AGRP (mRNA) m'zigawo za hypothalamus lonse mu makoswe anadyetsa chakudya cha 31.8% chokhudzana ndi chow controls. Komabe, ma level orexin mRNA ndi NPY mRNA sanasinthe. Motero, zotsatira za zakudya zamtundu wa mafuta / khalidwe labwino za paradigm zikuwonekera kuti ndi zachindunji kwa AGRP, ndipo sizinapangidwe kwa orexigenic neuropeptides. Izi zikugogomezera ntchito kwa AGRP pakulimbikitsa, kapena kufunafuna, chakudya, ndipo zimagwirizana ndi malipoti angapo atsopano m'mabuku (tafotokozedwa m'munsimu). Ntchito yathu ya posachedwapa yasonyeza udindo wapadera wa kusintha kwapakati pachitetezo chogwirizana ndi momwe ntchito ya PR imathandizira pazithunzi zathu, ndi kuchulukitsidwa kwa cFos muzinthu zingapo zamkati zosiyana (hypothalamic nuclei)). Tinazindikiranso kuti ARC ndi dera lofunika kwambiri la (insogin) insulin kuchepetsa sucrose kudzilamulira (). ARC ili ndi neurons AGRP / NPY (; ) zomwe zimagwira ntchito mkati mwa hypothalamus yomwe imapangitsa kuti kudyetsa ndi njira zambiri. Phunziro ili, kuwonetsa kwa immunocytochemical kuchulukitsa kwa AGRP neurons kunasonyeza kuwonjezeka kwa cFos / AGRP neurons mu makoswe omwe adaphunzitsidwa kuti aziyendetsa sucrose, poyerekeza ndi machitidwe osaphunzitsidwa a khalidwe. Imeneyi ndi njira yachiwiri yomwe imatanthauzira kuti AGRP neuronal activation imathandiza kuti (kuyambika kwa) kukhazikitse kudzilamulira. Zonse zakale komanso kafukufuku waposachedwa wagwirizanitsa kufotokoza kwa AGRP ndi kuchita ndi kudya mafuta, monga chakudya () kapena pa nkhani ya paradigm yokakamiza (); ndi makoswe akulu ICV AGRP amakonda kwambiri malo omwe amakonda mafuta (). Kafukufuku waposachedwapa pogwiritsa ntchito njira zamakono zovomerezeka zomwe zimalola kuvomerezedwa kwa AGRP neurons mu mbewa (; ) atsimikizira kuti AGRP imalimbikitsa kudyetsa, kumawonjezera chakudya, komanso imachepetsa ndalama zowonjezera mphamvu. N'zochititsa chidwi kuti m'magulu oyesera amadyetsa zakudya zamtundu wa mafuta, chiwerengero cha caloric chodyera chinali chochepa poyerekeza ndi makoswe odyetsedwa (Gulu 8), zomwe zingakhale zogwirizana ndi zotsatira zowonongeka za AGRP kuchepetsa kuchepa kwa magetsi. Zotsatira izi zimagwirizana ndi zofufuza zoyambirira za , zovuta zambiri za AGRP zokhudzana ndi mphamvu zamagetsi zingakhale zotalika. Choncho, monga njira yachitatu, zotsatira zathu zikuwonetsetsa kuti sucrose azidzilamulira okha ndi makoswe (a chow-federal) amphaka operekedwa ndi ICV AGRP amasonyezanso zomwe zikuchitika. Kuwonjezeka kwakukulu kwa AGRP mRNA poyera makoswe kudyetsa chakudya chambiri cha mafuta kwa milungu inayi chikugwirizana ndi kafukufuku waposachedwapa zomwe zimagwirizanitsa zosavuta mafuta mafuta, mavitamini omwe amachititsa mafuta, komanso kuwonjezeka kwa AGRP ku hypothalamic neurons. Motero, Kuonjezera kwa asile oleic kapena palmitic ku maselo a hypothalamic kumabweretsa kuwonjezeka kwa mawu a AGRP. Ngakhale zakudya zomwe timagwiritsa ntchito zinali ndi stearic, palmitic, ndi oleic acid, sizingatheke kudziwa ngati mafuta awa aliwonjezeka mu mu vivo hypothalamic milieu, kaya zochitika zawo zapadera zingagwirizane ndi zakudya zam'thupi za mafuta, ndipo ngati chimodzi kapena zambiri mwa izi zidzatsogolera kukulengeza kwa AGRP. Ngakhale zili choncho, zimayesa kulingalira kuti anthu omwe ali ndi zakudya zowonjezera amathandizira kuwonjezereka kwa maswiti kudzera muchithunzi choyambirira pa hypothalamus yamkati.

Gulu 8  

Mapulogalamu Oyesera: Kcal Idatha

Phunziro lathu likuwonetsa kuti makoswe aang'ono awonjezera chikoka cha sucrose poyerekeza ndi makoswe akuluakulu. Izi zidawonekera pa nthawi yonse ya PR kudzilamulira, ndipo panali chizoloŵezi cha zakudya zapamwamba za mafuta kuti zithetse msinkhu wa zaka. N'zotheka kuti izi sizinafikire chiwerengero cha ziwerengero chifukwa cha kukula kwake kwa gulu; Choncho, deta imasonyeza kuti muzilombo zakutchire (ndipo mwinamwake anthu) mafuta okwera kwambiri mu zakudya angapangitse kukhala ndi makhalidwe abwino ofunafuna kupeza zakumwa zotsekemera kapena zakudya. Kuchokera m'malingaliro a anthu, imatsindika kufunikira kochepetsetsa chigawo cha mafuta cha "tweens" kapena "achinyamata", osati chifukwa chokhalitsa, chotsutsana ndi zotsatira za mafuta owonjezera, koma chifukwa chakuti zingathandizire makhalidwe omwe amatsatira mu kudya kwambiri shuga. Monga tawonanso posachedwapa , kugwiritsira ntchito mankhwala a shuga ndi mafuta kungakhale ndi zotsatira zowonongeka kwambiri. Mafuta aakulu / kuphatikiza kwa shuga kwa anthu ndi zakudya zochepa zochepa (). Ndi kuchuluka kwa matenda a shuga () ndi chiwindi cha mafuta () zikuchitika m'mabungwe a ana, kufunikira kwa chakudya chamagulu ndi choyenera paunyamata ndi chowonekera. Tinawona kuwonjezeka kwakukulu kwa makina osindikizira omwe amalephera kugwira ntchito pamphaka (poyerekeza ndi makoswe akulu), ngakhale kuti chiwerengero cha makina achiwindi anali otsika kwambiri. N'zotheka koma zikuwoneka kuti sizingatheke kuti kuyimitsa kotsitsika kogwira ntchito kungakhale ngati 'chosalongosola' zotsatira za ntchito yonse, monga ntchito yambiri inali cholinga-chotsogoleredwa ku chiwindi chogwira ntchito. Ngakhale kuti nambala yeniyeni ya makina osokoneza bongo anali owonjezereka, chiwerengero cha makina opangidwira amatsenga anali ofanana pakati pa makoswe akuluakulu ndi akuluakulu, ndipo makina owonjezera a lever angasonyeze nthawi yogwira ntchito m'zipinda zodzilamulira. Mu mtundu wina wosiyana (zakudya zina zoletsedwa, kugwiritsa ntchito mapepala a zakudya osati mphoto yokoma, ndi ndondomeko ya FR1) posachedwapa adasintha machitidwe a achinyamata pa makoswe akuluakulu. Iwo sankawona kusiyana kulikonse mu mphuno za mphuno zomwe zinkapereka mapepala a zakudya, pakati pa makoswe aang'ono ndi akuluakulu. Komabe, iwo anawona khalidwe lopitirizabe kupirira panthawi yotha, mu makoswe a ana. Kuphatikizidwa pamodzi, maphunziro awiriwa akutsindika za msinkhu wa msinkhu komanso chitukuko chachitukuko pa zofuna za chakudya, mogwirizana ndi kukula kwa makoswe a pubertal. Mu phunziro lino ife tinayesa amuna, koma osati akazi, makoswe. Pakali pano pali maphunziro ochepa poyerekeza makoswe amphongo ndi abambo pa zokondweretsa chakudya, komanso kuwonetsetsa nthawi yomwe nthawi yobwereza ikuyenera. Tiyenera kukumbukira kuti mu phunziro la (achinyamata) achinyamata, anaona mgwirizano pakati pa chizindikiro cha kukula, osati gonadal steroids pa se. Komabe, zotsatira za kugonana m'zaka zino zikuyeneranso kufufuza.

Pomalizira, maphunziro athu amasonyeza chidwi chowonjezereka cha sucrose mu makoswe otha kufalitsa poyerekeza ndi akulu, ndipo izi zimalimbikitsidwa ndi kupeza chakudya chokwanira kwambiri. Zotsatira za zakudya zamtundu wapatali pa sucrose zifukwa zingakhale zogwirizanitsa ndi ntchito yowonjezera ya AGRP mu hypothalamus yamkati. Uwu ndi umboni wina wokhudzana ndi mphamvu ya CNS yomwe imayendetsa magetsi oyendetsa mphamvu zowonjezera mphamvu zamagetsi ndi magulu ozungulira omwe amayang'anira mphotho ndi zolinga. Kupititsa patsogolo zofuna za sucrose ndi zakudya zamtengo wapatali kwambiri zimayambitsa kusokoneza maganizo kwambiri ndi kunenepa kwakukulu ndipo zimasonyeza kuti khalidwe lingayambe kusintha kayendedwe kamadzimadzi, osati mosiyana. Kusakaniza kwa mafuta okwera kwambiri, ndi zakudya zokoma zokhala ndi fructose, zomwe zimagwirizanitsa pamodzi zimathandizira kuwonetsa kagawidwe kamene kamakhala koopsa kwambiri kwa mtundu wa XXIMUM ndi matenda a mtima. Zotsatirazi zikugogomezera kufunikira koyang'ana pa zakudya ndi zakudya pa nthawi ya kutha msinkhu, osati kuthandizidwa ndi zokhudzana ndi zachilengedwe komanso zachilengedwe, komanso ndi kusintha kwa njira za CNS ndi kusintha kwa khalidwe monga zinyama kapena kusintha kwa anthu kupyolera mu kusintha kwa maiko ambiri za luso la kubereka.

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  • Zakudya zapamwamba kwambiri za mafuta zimapangitsa kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda tizilombo toyambitsa matenda.
  • Mu phunziro ili, kudya kwakukulu kwa mafuta kumapangitsa sucrose kukhala ndi zifukwa mu makoswe a peri-pubertal.
  • Nthiti za Peri-pubertal zinawonjezera sucrose zizindikiro poyerekeza ndi akuluakulu.
  • Zowonjezera sucrose zifukwa zingakhale zotsatizana ndi hypothalamic AGRP.
  • Kutsirizitsa: Zakudya zamtundu wapamwamba zimayambitsa zowonjezera m'malo mopitirira kunenepa kwambiri.

Kuvomereza

Kafukufukuyu adathandizidwa ndi thandizo la NIH DK40963. Dianne Figlewicz Lattemann ndi Senior Research Career Scientist, Biomedical Laboratory Research Program, Dipatimenti ya Veterans Affairs Puget Sound Health Care System, Seattle, Washington. Stefano Benoit anathandizidwa ndi NIH DK066223 ndi Ethicon Endosurgery Inc. Olembawo amayamikira Dr. Tami Wolden-Hanson kuti athandizidwe ndi miyezo ya thupi; Dr. William Banks ndi Lucy Dillman kuti athandizidwe ndi mayendedwe a triglyceride; ndi Amalie Alver, ndi Samantha Thomas-Nadler kuti athandizidwe ndi maphunziro a khalidwe.

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