Kunenepa Kwambiri: Kugonana ndi Kuteteza (2014)

Yi Zhang,^1,2,* Ju Liu,¹ Jianliang Yao,¹ Gang Ji,³ Qian yautali,⁴ Jing Wang,¹ Guansheng Zhang,¹ Jie Tian,¹ Yongzhan Nie,³ Yi Edi. Zhang,^2,5 Mark S. Gold,² ndi Yijun Liu^2,4,6,*

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Kunenepa kwambiri kumayambitsa vuto lalikulu la thanzi la zaka za 21st. Amalimbikitsa matenda opatsirana monga matenda a mtima, mtundu wa 2 shuga, obstructive apnea, mitundu ina ya khansa, ndi osteoarthritis. Kuwonjezera mphamvu zowonjezera mphamvu, kusagwiritsidwa ntchito kwa thupi, komanso matenda a chibadwa ndizo zimayambitsa matenda olemera kwambiri, pamene kusintha kwa majini, matenda a endocrine, mankhwala, kapena matenda a maganizo angakhale omwe amachititsa nthawi zina. Kupititsa patsogolo ndi kukonzanso kunenepa kungaphatikizepo njira zofunikira zogwiritsira ntchito pathophysiological monga matenda osokoneza ubongo m'madera ozungulira komanso mahomoni osagwirizana ndi neuroendocrine. Kudya ndi kuchita masewera olimbitsa thupi kumapangitsa kuti munthu asamakhale wathanzi kwambiri, komanso mankhwala osokoneza bongo angatengedwe pothandizira kuchepetsa kudya kapena mafuta. Opaleshoni ya bariatric ikhoza kuchitidwa ndi odwala owonjezera kwambiri kuti achepetse mphamvu ya m'mimba ndi kuyamwa kwa zakudya, ndikupangitsanso mofulumira. Ndemangayi imapereka chidule cha mabuku pa zovuta za matenda a kunenepa kwambiri ndikukambirana njira zoyenera zothetsera kunenepa kwambiri.

3.1. Kudya Kwambiri

Kudya kosokonezeka ndi njira zosalemetsa zowononga ndizofala pakati pa achinyamata, zomwe zingawaike pangozi ya vuto la kudya. Matenda odyera amakhala okhudzidwa, otsika kwambiri, komanso odwala ambiri komanso odwala. Choncho, kufunika kozindikiritsa koyambirira ndi kupewa matenda okhudzana ndi zakudya kumakhala nkhani yofunikira yomwe imafuna kuti anthu azisamalidwa kwambiri kuchokera kuntchito zapadera [18,19].

Matenda obwera chifukwa cha kudya (BED) ndi matenda omwe amadya kwambiri anthu akuluakulu. Matendawa amakhudza thanzi la munthu ndi thanzi lake ndipo ndizofunika kwambiri za thanzi labwino [20,21]. Pafupifupi 2.0% ya amuna ndi 3.5% azimayi amanyamula matendawa moyo wawo wonse -kuposa matenda omwe akudziwika bwino a anorexia nervosa ndi bulimia nervosa [20]. BED imakhala ndi kudya mowa mopanda kudya popanda kutsuka zigawo zina ndi kusonkhana ndi kukula kwa kunenepa kwakukulu [22]. Anthu omwe ali ochepa kwambiri komanso omwe ali ndi BED nthawi zambiri amakhala olemera kwambiri kuposa omwe sali ndi vuto [23]. Angathenso kutaya ndi kuchepetsa kulemera, kapena kukhala hypervigilant za kulemera [23]. Nthawi zambiri zimaphatikizapo zakudya zomwe zili ndi mafuta, shuga, ndi / kapena mchere, koma mavitamini ndi minerals, ndipo zakudya zoperewera zimakhala zofala kwa anthu omwe ali ndi BED [21,23]. Anthu nthawi zambiri amakhumudwa chifukwa cha kudya ndi kudya komanso amadwala nkhawa. Anthu ovutika omwe ali ndi BED ali pangozi yowonongeka kwambiri yomwe imakhudzana ndi kunenepa kwambiri monga mtundu wa 2 shuga, matenda a mtima (mwachitsanzo, kuthamanga kwa magazi ndi matenda a mtima), vuto la m'mimba (mwachitsanzo, matenda a ndulu), mavitamini ambiri a m'magazi, matenda a minofu,20,21]. Nthawi zambiri amakhala ndi moyo wapansi ndipo amakhala ndi mavuto ambiri [21]. Anthu ambiri omwe ali ndi matenda oledzeretsa adayesa kudziletsa okha, koma amalephera kuyesa nthawi yaitali.

3.2. Chakudya Chakudya

Zizindikiro za BED zimakhala zikuwoneka ndi zizolowezi zoledzera (mwachitsanzo, kuchepetsa kuchepetsa ndikupitiriza kugwiritsa ntchito zinthu ngakhale zotsatira zoipa). Umboni ukuwonjezeka pothandizira kugwiritsidwa ntchito mowa mwauchidakwa [24]. Zitsanzo za zinyama zimasonyeza mgwirizano pakati pa kudya ndi kudya mowa ngati chakudya. Makoswe amapatsidwa chakudya chogwiritsidwa ntchito kwambiri (mwachitsanzo, shuga ndi mafuta) zisonyezero za khalidwe la kudya mowa, monga kudya chakudya chokwanira mu nthawi yochepa ndikufuna zakudya zopangidwa bwino kwambiri mosasamala kanthu za zotsatira zake zoipa (mwachitsanzo., zodabwitsa zamagetsi) [25,26]. Kuwonjezera pa kusintha kwa khalidwe, makoswe amasonyezanso kusintha kwa nsomba zomwe zimakhudza kumwa mankhwala osokoneza bongo, monga kuchepetsedwa kwa dopamine D2 receptor kupezeka [26]. Deta iyi imasonyeza kuti BED ikhoza kukhala chisonyezero chimodzi cha chizolowezi cha zakudya [24].

Kaya kapena kunenepa kwambiri kumaphatikizapo kuledzera kwa anthu ena ovuta kwambiri akadakalibe. Kuchuluka kwa deta kumapangitsa kuti lingaliro lakuti kudya kowonjezera zakudya kungayendetsere makhalidwe ozunguza [27]. Zizoloŵezi zina zoledzera, monga kulephera kuyesa kuchepetsa kudya zakudya kapena kupitiriza kudyetsa mosasamala kanthu za kusagwedezeka kolakwika, kumawonetsa muzovuta kudya zakudya [27]. Ubongo umawonekeranso kuti umayankha zakudya zokoma kwambiri mu mafashoni ena ofanana monga momwe zimakhudzira mankhwala osokoneza bongo [28]. Lingaliro lenileni ndilokuti zakudya zina kapena zowonjezera zowonjezeredwa ku zakudya zingayambitse njira yowidetsa anthu omwe amatha kutengeka [29]. Njira yogwiritsira ntchito mankhwala osokoneza bongo ndi yosawerengeka ngati vuto lokhalanso labwino lomwe limadalira zinthu zomwe zimakulitsa zilakolako za chakudya kapena zinthu zokhudzana ndi zakudya ndi kukulitsa chisangalalo, malingaliro, ndi zolinga [30,31,32,33,34].

Yale Rudd Center for Food Policy ndi Kulemera Kwambiri, kafukufuku wopanda phindu ndi bungwe la ndondomeko ya anthu, inafotokozedwa mu 2007 zomwe zimagwirizanitsa ndi kugwiritsa ntchito ndi kuchotsa mitundu ya shuga ndi mankhwala osokoneza bongo, komanso kugwirizanitsa pakati pa kudya ndi kugwiritsa ntchito mankhwala osokoneza bongo (mwachitsanzo, anthu amakonda kulemera pamene asiya kusuta kapena kumwa). Izi zikutitsimikizira kuti zowonjezera kuti chakudya chokoma komanso mankhwala ozunguza bongo angapikisane ndi njira zofanana zokhudzana ndi ubongo [35,36]. The Rudd Center inathandiza kulenga Yale Food Addiction Scale (YFAS), yomwe yapangidwa kuti izindikire zizindikiro za chizoloŵezi choledzeretsa ku mitundu ina ya zakudya zomwe zili ndi mafuta akuluakulu komanso shuga [37,38]. Gearhardt ndi mnzake [39] posachedwapa anafufuza ubongo kuti apereke chakudya kwa odwala okhala ndi zosiyana zosiyanasiyana pa zakudya zowonjezera zakudya. Odwalawo ankadziwitsidwa kuti akubwera posakaniza chocolate milkshake kapena njira yothetsera vuto, kapena amapatsidwa chokoleti cha milk chocolate kapena mankhwala osakwanira [39]. Zotsatirazo zikuwonetsa mgwirizano pakati pa zida zapamwamba zowonjezera zakudya ndi kuwonjezereka kwa zigawo za ubongo zomwe zimalimbikitsa zifukwa za chakudya, monga amygdala (AMY), kapangidwe ka amtundu (ACC), ndi orbitofrontal cortex (OFC). Zinachitika kuti anthu oledzeretsa akhoza kuchitapo kanthu pazinthu zofunikira, ndipo kuti kuyembekezera kwa mphotho pamene chidziwitso chimawonekere chingapangitse kudya chakudya chokwanira [39]. Kawirikawiri, kumwa mowa mwauchidakwa sikunenedwa bwino ndipo kungayanjane ndi vuto la kugwiritsa ntchito mankhwala [40] ndi matenda ovutika. N'zochititsa chidwi kuti DSM-5 yasankha zochitika zowonongeka podziwa matenda ozunguza bongo [41] monga chithandizo chodziimira kwaulere ndikugwiritsanso ntchito gulu la Matenda Odya monga Kudya ndi Kudyetsa Matenda.

3.3. Prader-Willi Syndrome (PWS)

Matenda a Prader-Willi (PWS) ndi matenda osokoneza bongo omwe amachititsa kuti hyperphagia komanso ubwana wawo asamakhale olemera kwambiri [42]. Odwala PWS amasonyeza makhalidwe ambiri odyera oledzera [43]. Kafukufuku wa Neuroimaging mu chikhalidwe ichi cha anthu odwala matenda odwala matendawa akhoza kutulukira njira zogwiritsira ntchito matenda opatsirana pogwiritsa ntchito zakudya zoperekera zakudya kapena kutaya zakudya zowonongeka. Chimodzi mwa zizindikiro za matendawa ndizovuta kwambiri kuti asamadye chakudya komanso zakudya zopanda zakudya. Kuchulukitsanso komanso kupweteka kwapadera komwe kumapangidwa ndi zinthu zowonjezera zomwe zimapangitsa kuti izi zitheke [42,43,44,45,46,47,48,49,50]. Kafukufuku wogwira ntchito zapamwamba apenda kufufuza zosavuta za magetsi oyendetsa odwala omwe amagwiritsidwa ntchito pogwiritsa ntchito maonekedwe a odwala PWS [44]. Poyankha masomphenya apamwamba- molimbana ndi Odwala a PWS omwe amawathandiza kuti asamawonongeke, amaonetsa kuchepa kwa chizindikiro cha hypothalamus (HPAL), insula, ventromedial prefrontal cortex (VMPFC), ndi nucleus accumbens (NAc) [44], koma osakhudzidwa kwambiri m'magulu ndi m'mapiri a paralimic monga AMY omwe amayendetsa khalidwe la kudya komanso m'madera monga mapepala apakati omwe amalepheretsa kudya zakudya [47,51]. Kuwonjezeka kwa HPAL, OFC [46,51,52], VMPFC [49], kumbali yapakati yapakati, kumsika kwapansi, kutsogolo kwakukulu, ndi maiko ena onse a ACC anawonanso [48,52,53]. Gulu lathu linapanga phunziro la mpumulo wa fMRI (RS-fMRI) kuphatikizapo kufufuza kwachangu (FC) ndikuzindikiritsanso kusintha kwa mphamvu FC pakati pa zigawo za ubongo mumasewu osayenerera, makina oyambirira, makina oyendetsa magalimoto, ndi makina oyendetsa makina a prefrontal cortex , motsatira [53]. Ife posachedwapa tagwiritsa ntchito njira zowonongeka za RS-fMRI ndi Granger kuti tifufuze zowonongeka zochititsa chidwi pakati pa njira zazikulu za neural zomwe zimayambira kudya kwambiri PWS. Deta yathu inavumbulutsira zowonongeka kuchokera ku AMY kupita ku HPAL komanso kuchokera ku MPFC ndi ACC mpaka AMY. Mwachidule, PWS ndikumapeto kwamtundu waumunthu wa kunenepa kwambiri ndi makhalidwe osadetsedwa. Kufufuza kafukufuku wokhudzana ndi matenda a PWS komanso kugwirizana ndi kugonjera mankhwala kungathandize kumvetsetsa bwino kayendedwe ka kudya ndi kudya zakudya [39,43].

4.1. Leptin

Hormone ya anorexicic yomwe imapangidwa kuchokera ku minofu ya adipose, leptin imayendera lipid metabolism mwa kuchititsa lipolysis ndi kuletsa lipogenesis [62]. Leptin imadutsa malire a ubongo mwaubongo kudzera mu kayendetsedwe ka kayendetsedwe ka saturable ndipo imatchula momwe thupi limagwirira ntchito (yosungirako mphamvu) ku malo osungirako zinthu [63]. Kamodzi kogwiritsidwa ntchito pakati pa receptor, leptin imatha kuchepetsa kudya-kuyambitsa matenda a neuropeptides (mwachitsanzo, NPY, AgRP) pamene akulamulira kwambiri mankhwala osokoneza bongo a alpha-melanocyte-stimulating-hormone, cocaine- ndi amphetamine-regulated, komanso corticotropin-release hormone [63]. Ziphuphu zamtundu wa leptin ndi leptin receptors zimabweretsa kuopsa koyambirira kwa kunenepa kwa ana [64]. Mavuto a Leptin m'magazi amakula kwambiri, ndipo amalimbikitsa kuti leptin ikhale yovuta kwambiri. Kukhalapo kwa leptin kukana kungapereke tsatanetsatane wa tsankho la hyperphagia odwala omwe ali ndi PWS omwe ma sevine awo a leptin ali aakulu kwambiri [64]. Anthu omwe amayamba kumwa mankhwalawa akhoza kukhala ndi leptin, zomwe zingachititse kudya kwambiri [65]. Mmene Leptin amakhudzidwira ndi makhalidwe odyetsa komanso osakhala oledzera akhoza kupitilizidwira pang'ono kudzera mwa njira ya disolimbic ndi / kapena nigrostriatal DA. Monga momwe kufufuza kwa fMRI kunasonyezera, kuonjezera leptin kunachepetsera chakudya chokwanira ndi kupatsa chakudya chowonjezereka panthawi ya zakudya pogwiritsa ntchito mankhwala osokoneza bongo mu statum mu maphunziro a anthu omwe alibe leptin [66]. Leptin monotherapy, komabe, sizinapambitse kuchepetsa chakudya chokwanira ndi kulemera kwa anthu okhwima monga poyamba anali kuyembekezera, mwinamwake chifukwa chotsutsana ndi leptin kukonda kwambiri kunenepa [67]. Komabe, mankhwala owonjezera a leptin amatha kukhala othandiza kuchepetsa phindu la phindu la chakudya [68] ndikuthandizani kusunga kulemera kwake.

4.2. Insulini

Insulin ndi hormone yamadzimadzi yovuta kwambiri yokonza glucose homeostasis. Insulini imadzuka pambuyo pa chakudya kuti magazi asapangidwe. Zakudya zamadzimadzi zambiri zimasinthidwa ndikusungidwa m'chiwindi ndi minofu monga glycogen, komanso mafuta mu tiyi tomwe timapanga. Matenda a insulin amasiyana mosiyana, ndipo kuchuluka kwa mafuta a visceral kumayenderana kwambiri ndi mphamvu ya insulini [69]. Kusuta ndi postpandial insulin ndi oposa kwambiri kuposa anthu oonda [70]. Insulin ikhoza kudutsa m'magazi a ubongo wa ubongo ndipo imamangiriza kwa opezeka m'magulu othamanga a hypothalamus kuti achepetse kudya [71]. Central insulin kukana kungabweretse kunenepa kwambiri, mofananamo ndi pakatikati leptin kukana amene akuganiza kuti ndibwino kuti mafuta otsika kwambiri kapena chitukuko cha kunenepa kwambiri [72,73]. Phunziro la positron la tomography (PET) linapangitsa kuti munthu asatetezedwe ndi insulini m'madera otetezeka a ubongo ndipo amatsutsa kuti kukana koteroko kungafune kuti ubongo wa insulin ukhale wapamwamba kuti athe kupeza mphotho yeniyeni komanso zakudya zomwe zimadya [74]. Mofanana ndi leptin, insulini imatha kuyendetsa njira ya DA komanso njira zogwirizana ndi kudya. Leptin ndi insulin kukana mu ubongo DA njira zingayambitse kudya zakudya zolimbitsa poyerekeza ndi leptin- ndi insulin-sensitive conditions kuti apange mphotho yokwanira yankho [75].

Kuphatikizana pakati pa njira yapakati ndi yowonongeka kwa mahomoni kumakhala kovuta. Mwachitsanzo, ghrelin imayambitsa mphotho ya dopaminergic, pamene leptin ndi insulin zimaletsa maderawa. Kuwonjezera apo, kuwonetsa maulendo onse a HPLA ndi ARC amalandira zizindikiro zozizwitsa zamaganizo ndi ntchito ndikutumiza uthenga kumadera ena a ubongo, kuphatikizapo midbrain dopaminergic mphotho malo [31].

4.3. Ghrelin

Ambiri amabisika m'mimba, ghrelin ndi peptide yeniyeni yomwe imachita mitsempha ya hypothalamic yomwe imakhala ndi ghrelin receptors kuti ikhale ndi zotsatira zamagetsi [76]. Ghrelin imapangitsa kuti anthu adye chakudya mwa njira zonse zomwe zimagwirizanitsa pakati pa mimba, HPAL, ndi hypophysis [77,78]. Ghrelin akuwoneka kuti akuyambitsa kudya ndi nsonga zapamwamba za seramu isanayambe kudya chakudya ndi kuchepetsa zigawo pambuyo pake [79]. Ghrelin akhoza kukhala ndi mphamvu yowonjezera mphamvu, powona kuti nthawi yaitali ghrelin administration ikuwonjezera chidziwitso [77,80]. Serum ghrelin ndizomwe zimakhala zochepa kwambiri poyerekezera ndi kulemera kwa anthu enieni komanso kuwonjezeka moyenera ndi kuchepetsa kunenepa kwambiri, kusonyeza kugwirizana kosagwirizana ndi BMI zapamwamba [81,82]. Ghrelin amachititsa kuti zigawo za ubongo zikhale zofunikira kwa hedonic ndi mayankho olimbikitsa ku zakudya zomwe zimadya [83]. Izi zikuphatikizapo kuyambitsa dopamine neurons mu VTA ndi kuchuluka kwa dopamine ku NAC ya ventral striatum [84]. Zotsatira za mphoto processing mu macholimbic dopaminergic njira ingakhale mbali yofunika ghrelin's orexigenic [83], motsimikiziridwa ndi umboni wakuti kutseka ghrelin receptors mu VTA kumachepetsa kudya chakudya [84].

4.4. Peptide YY (PYY)

PYY ndi yaifupi, 36-amino acid peptide yopangidwa mu leamu ndi colon powyankha. Pambuyo pa kuyamwa kwa chakudya, PYY imatulutsidwa ku L-maselo kumbali ya distal ya m'matumbo aang'ono. Amachepetsa mlingo wa m'mimba motility ndi ndulu ndi chifuwa chotsitsa ndipo amachepetsa chilakolako cha zakudya komanso amachititsa kuti [85,86]. PYY amagwira ntchito kudzera m'mimba ya vagal, NTS mu ubongo, ndi hyperhalamus yokhudza proopiomelanocortin (POMC) neurons [87]. Anthu ochepa amatha kusungira PYY zochepa kusiyana ndi anthu osakhala ochepa kwambiri ndipo ali ndi ziŵerengero zochepa za seramu ghrelin [88]. Motero, PYY m'malo mwake angagwiritsidwe ntchito pochiza thanzi ndi kunenepa kwambiri [88,89]. Inde, kudya kwa caloric pa chakudya chamadzulo kunaperekedwa maola awiri PYY kulowetsedwa kunachepetsedwa ndi 30% mu maphunziro ovuta kwambiri (p <0.001) ndi 31% m'maphunziro owonda (p <0.001) [89]. Kuchuluka kwa kuchepetsa kunali kochititsa chidwi kwambiri poyamba. Ngakhale kuti anthu olemera kwambiri amasonyezedwa kuti ali ndi zigawo zochepa za PYY pambuyo pake, amawonekeranso kuti amawoneka mwachibadwa ku zotsatira za anthectic za PYY3-36. Kuphatikizidwa, kunenepa kwambiri kungakane ndi vuto la PYY lakumverera, ndipo zotsatira za anthectic za PYY zingakhale njira zothandizira kupanga mankhwala osokoneza bongo [90].

4.5. Glucagon-Monga Peptide 1 (GLP-1)

GLP-1 ndi hormone yamtengo wapatali yomwe imatulutsidwa ndi PYY kuchokera kumatumbo a m'mimba m'mimba mwa mazira atatha kudya. Imalembedwa mwa mitundu iwiri yofanana, GLP-1 (7-37) ndi GLP-1 (7-36) [91]. GLP-1 imagwira ntchito makamaka pofuna kulimbikitsa kusungunuka kwa shuga, kuteteza β-selo kukula ndi kupulumuka, kulepheretsa kutuluka kwa glucagon, ndi kupondereza chakudya [92]. Utsogoleri wa pulogalamu ya GLP-1 imachepetsa chakudya chokwanira ndikuwonjezera chidzalo mwa anthu mbali imodzi mwa kuchepetsa kupatsa m'mimba komanso kulimbikitsana chapakati [93]. Maseŵera a plasma a GLP-1 ndi apamwamba kwambiri asanayambe kudya komanso atadya chakudya poyerekeza ndi anthu olemera kwambiri, pamene mapulogalamuwa akugwirizana ndi kusala kudya kwapang'ono pomwe GLP-1 ndi kutulutsidwa kwapadera [94]. Njira zowonongeka zogwiritsidwa ntchito ndi njira zothandiza kuchepetsa kunenepa kwambiri. Pakalipano, deta ndi yochepa pokhudzana ndi kusintha kwa GLP-1 ku odwala owonjezera pambuyo pa opaleshoni [95].

4.6. Cholecystokinin (CCK)

Cholecystokinin (CCK), mahomoni ambiri omwe amapezeka m'matumbo ndi ubongo, amathandizira kuthetsa chilakolako chofuna kudya, khalidwe losasangalatsa, komanso kutaya kwachisawawa kudzera ponseponse ndi njira zofunikira. CCK imakhudzanso njira zakuthupi zokhudzana ndi nkhawa, khalidwe la kugonana, kugona, kukumbukira, ndi kutupa m'mimba [95]. CCK imayimira misonkho ya mahomoni osiyanasiyana mosiyana ndi kuchuluka kwa chiwerengero cha amino acid (mwachitsanzo, CCK 8 mu ubongo, ndi CCK 33 ndi CCK 36 m'matumbo). Mahomoni osiyanasiyanawa sawoneka mosiyana kwambiri ndi zakuthupi. CCK yomwe imachokera m'matumbo imamasulidwa mwamsanga kuchokera ku chikhomo cha jaodal ndi jejunal chifukwa cha zakudya zowonjezera zakudya zowonjezera za 15-30 min post, ndipo zimakwera mpaka 5 h [96]. Ndizolimbikitsa kwambiri mphamvu zamadzimadzi m'mimba komanso bile kuchokera ku gallbladder [63]. CCK imachedwetsa m'mimba kutaya komanso kumalimbikitsa m'mimba motility. Monga neuropeptide, CCK imayambitsa ma receptors pa vagal afferent neurons, omwe amachititsa zizindikiro zogwiritsira ntchito poyerekeza ndi hypothalamus. Izi zimachititsa kuti NPY ikhale ndi nthenda yambiri ya mankhwala ndipo imapereka ndemanga kuti achepetse kukula kwa chakudya ndi nthawi ya chakudya [97].

Mwachidule, zizindikiro za mahomoni zomwe zimatulutsidwa mu thirakiti la GI (ghrelin, PYY, GLP-1, ndi CCK), mphukira (insulin), ndi minofu ya leptin imapanga chigawo chofunika kwambiri mu chiwongolero cha ubongo. , kugwiritsa ntchito mphamvu, komanso kunenepa kwambiri. Ngakhale kuti leptin ndi insulini zingawonedwe kuti zimakhala zogwiritsira ntchito mphamvu zogwiritsira ntchito mphamvu, ghrelin, CCK, peptide YY, ndi GLP-1 ndizithunzithunzi zokhudzana ndi kuyambitsa chakudya ndi kutha. Mahomoni awa ndi ma peptides amasintha chilakolako cha kudya ndi makhalidwe odyera pogwiritsa ntchito hypothalamic ndi brainstem nuclei ndipo mwinamwake pa njira ya dopaminergic m'katikati mwa mphotho; iwo asonyeza kuti zingakhale zovuta zothandizira zotsutsana ndi kunenepa kwambiri.

5.1. Kugwiritsa Ntchito Neuroimaging

Poyerekeza ndi mayankho a ubongo ku zithunzi za zakudya zapamwamba (mwachitsanzo, ma hamburgers), zakudya za calorie (mwachitsanzo, masamba), zida zogwirizana ndi kudya (mwachitsanzo, makapu), ndi mafano osalowererapo (mwachitsanzo, mathithi ndi minda), ntchito fMRI Kafukufuku apeza ubongo waukulu kwambiri kuti ukhale ndi zakudya zamakono molimbana ndi Zithunzi zosaloŵerera m'zinthu zowonjezera (mphoto / zifukwa), insula yam'kati (kulawa, kutsegula, ndi kutengeka), HIPP (kukumbukira), ndi pataetal cortex (malo ochepa) mu maphunziro achikazi oposa omwe ali ochepa [99]. Kuwonjezera pamenepo, NAC, yapakati ndi yomaliza ya OFC, AMY (maganizo), HIPP ndi MPFC (zolimbikitsa ndi ntchito yaikulu), ndi ACC (kugonjetsa kusamvana / kupotoza maganizo, chidziwitso cha chidziwitso, ndi maphunziro opindula) zimasonyezeranso kuwonetseratu kuti zithunzi za zakudya zakutali kwambiri molimbana ndi Osati zakudya ndi / kapena zithunzi zochepa zamakono [100]. Zotsatira izi zikuwunikira mgwirizano pakati pa mayankho a cortical ndi zakudya ndi kunenepa kwambiri ndipo zimapereka chidziwitso chofunikira pa chitukuko ndi kukonzanso kunenepa kwambiri [101].

Ntchito yokhudzana ndi ubongo yosagwirizana ndi chakudya sikuti imangotenga mbali zokhazokha zokhazokha, komanso maulendo a neural omwe amawoneka kuti ali ndi mphamvu zoletsera komanso m'dera lachimake. Kafukufuku wa PET adafotokoza kuti kuchepa kwa hypothalamic, thalamic, ndi limbic / paralimic zovuta kwambiri (BMI ≥ 35) zotsalira (BMI ≤ 25) amuna [101]. Soto-Montenegro Et al. ndi Melega et al. [102,103] anafufuza kusintha kwa ubongo wa shuga m'magazi pambuyo polimbikitsidwa kwambiri mu ubongo (DBS) mu malo otha msinkhu (LHA) mu khola la kunenepa kwambiri pogwiritsa ntchito kujambula kwa PET-CT. Anapeza kuti chakudya chambiri pa tsiku loyamba la 15 chinali chochepa m'matenda ochiritsidwa ndi DBS kuposa nyama zomwe sizinakopedwe. DBS yowonjezera kagayidwe kamene kamayambitsa matenda m'thupi, malo a subiculum hippocampal, ndi AMY, pamene kuchepa kwa mitsempha ya m'magazi kunalembedwa mu thalamus, caudate, cortex, ndi cerebellum [102,104]. DBS inapanga kusintha kwakukulu m'madera a ubongo okhudzana ndi kuyendetsa chakudya ndi ubongo wa ubongo, mwinamwake mwa kuwonetsa zovuta za hippocampal zomwe zikuwonetsedwa mu makoswe oposa. Phindu laling'ono mu gulu la DBS likusonyeza kuti njirayi ingaganizidwe ngati njira yothetsera kunenepa kwambiri [102]. PET ndi SPECT zakhala zikugwiritsidwa ntchito pophunzira zolakwika za ubongo pansi pa zochitika zosiyanasiyana [105,106,107,108,109,110,111].

Zomwe zinakhazikitsidwa pokhapokha pokhapokha zatha (50% ya Resting Energy Expenditure) (Daily Revenue Energy Expenditure) (REE) yomwe imaperekedwa kwasungidwe ka chakudya chamadzimadzi pambuyo pa 36 yomwe imasungira PET (PET). kuphunzira [101], ngakhale kuti kufufuza kwina ndi kusonkhanitsa deta yowonjezereka pogwiritsa ntchito ufa wosiyana wa chakudya kumatsutsa izi. Kumbali inanso, kuchepa kwachinsinsi ku dlPFC muzowonjezereka (BMI ≥ 35) molimbana ndi akulu (BMI ≤ 25) akuluakulu ankasungidwa mozama mu maphunzirowa ndi ena [112]. Kufufuza kwa akuluakulu achikulire kunazindikira mgwirizano waukulu pakati pa mawere a m'mimba / BMI ocheperapo ndi kuchepetsa kutsegulira fMRI kuti likhazikike m'malo okhudza ubongo wa DA, ndi pakati pa kuyankha kwa chinyengo ndi kunenepa kwambiri kwa akulu akulu kusiyana ndi achikulire [98]. Kuphatikizidwa, kuchepa kwa dopamine ntchito kumapereka malingaliro amodzi olemetsa olemera komanso olemera akuluakulu [113]. Cholinga chachikulu cha maphunzirowa ndi chakuti kunenepa kwambiri kumagwirizanitsidwa ndi machitidwe osamvetsetseka ku zochitika zowonongeka m'makono a ubongo omwe amasonyezedwa mu mphotho / zolimbikitsa ndi kutengeka maganizo. Kudya mopitirira muyeso kwa anthu ovuta kwambiri kungakhale kogwirizana ndi kuphatikizapo mankhwala osokoneza bongo a homeostatic kumalo osokonezeka mu hypothalamus, ndi kuchepetsa ntchito za DA njira ndi mayendedwe oletsedwa mu dlPFC [98].

Ngakhale kuti tikudziwa bwino za njira zamagetsi zoyendetsa zakudya ndi kunenepa kwambiri, sizikudziwikiratu ngati kuchepa kwa njira zothandizira kumatsogolera kapena kutsata kudya mopitirira muyeso kapena kunenepa kwambiri. Maphunziro a pulogalamu yapamwamba yopanga mapuloteni m'makina a makoswe omwe amapeza zakudya zomwe zimapangitsa kuti kunenepa kwambiri (mwachitsanzo, kuyerekezera zochitika zoganizira zisanafike, pakapita, ndi pambuyo pa chitukuko cha zakudya zowonjezera kwambiri komanso / kapena kutsatira caloric restriction pambuyo kunenepa kukhazikitsidwa) ndi anthu owonjezera pamaso ndi pambuyo opaleshoni bariatric, zomwe zimaletsa bwino kudya kwambiri ndi kuchepetsa kunenepa kwambiri, zingapereke zidziŵitso zofunika mu causal kapena chiyanjano choyenera pakati pa kudya kwambiri (kapena kunenepa kwambiri) ndi malamulo osokoneza bwalo lachizungu.

5.2. Zojambula Zachilengedwe

Umboni wam'mbuyo umasonyeza kusintha kwa ubongo kwa kusintha kwa ubongo [114]. Mwachitsanzo, kusanthula kwa MRI kunapangitsa kuti gulu likhale lofanana pakati pa thupi lolemera ndi kuchuluka kwa ubongo mkati mwa anthu [115]. Makamaka, mkulu wa BMI amachepetsa kuchepa kwa grey (GM) m'mphepete mwake, kuphatikizapo OFC, pansi penipeni, ndi pakati pambali, ndipo imayenderana kwambiri ndi mapepala omwe amapezeka [116,117,118] ndi dera lalikulu lachigawo cholondola lomwe likuphatikizapo parahippocampal (PHIPP), fusiform, ndi lingual gyri [114]. Kafukufuku wina ndi akuluakulu a 1428 anawonanso mgwirizano wolakwika pakati pa amuna ndi akazi omwe ali pakati pa BMI ndi onse GM, komanso m'magulu osiyana siyana omwe amachititsa kuti anthu azikhala ndi nthawi yochepa, occipital lobes, precuneus, putamen, gyrus, midbrain,116,118]. Kuphunzira mosiyana ndi anthu okalamba omwe anali okalamba omwe anali ovuta kwambiri (77 ± 3 zaka), olemera kwambiri (77 ± 3 zaka), kapena wotsamira (76 ± 4 zaka) adalemba mawu otsika mu thalamus (malamulo okhudzidwa ndi magalimoto), HIPP, ACC, ndi cortex yotsogolo [119]. Izi zidachitika kuti ubongo wamasinthidwewo unakhazikitsidwa chifukwa cha chiwerengero cha anthu akuluakulu, koma sichidziwikiratu ngati kusinthako kumayambira kapena kutsata kunenepa kwambiri. Ngakhale zili choncho, kuchepetsa mphamvu m'madera okhudzana ndi mphotho ndi kuyang'anira kungakhale koyenera kuti zisawonongeke poyenderana ndi kunenepa kwambiri ndipo zingakuthandizeni kufotokozera kwambiri kupitirira kwambiri kwa kunenepa kwambiri. Vuto lochepetsedwa m'magulu monga HIPP lingakhale mbali imodzi ya chiwerengero cha dementia [120,121] ndi kuchepa kwa chidziwitso [122] mwa anthu ovuta kwambiri. Kugonana kwa mpweya [123], kuchulukitsidwa kwa mahomoni adipocyte monga leptin [124], kapena kumasulidwa kwa zifukwa zowonjezera kutupa chifukwa cha mafuta ochuluka kwambiri zikhoza kukhala zochitika zapakati pambali pa kusintha kwa ubongo [125]. Zotsatirazi zikusonyeza kuti kukumbukira kwa hedonic kudya zakudya zina kungakhale kofunikira kwambiri pakuletsa kudya [98,126]. Purnell Et al. [127] anapeza kuti hyperphagia ndi kunenepa kwambiri zingakhale zokhudzana ndi kuwonongeka kwa hypothalamus mwa anthu. Inde, wodwala wamkazi mu phunziro ili ndi brainstem cavernoma yomwe inawonongeka njira zimayambira modzidzimutsa wa hyperphagia ndi kupindula kolemera kuposa 50 makilogalamu osachepera chaka chimodzi potsatira njira yochizira opaleshoni yokhala ndi midini ya suboccipital craniotomy. Kusokoneza malingaliro owonetsa anawonetsa kutayika kwa mitsempha ya mitsempha pakati pa ubongo wake, hypothalamus, ndi malo apamwamba a ubongo koma kusungidwa kwa magalimoto. Karlsson Et al. [128] anaphunzira maphunziro a 23 ovuta kwambiri komanso odzipereka omwe sali odzipereka kwambiri kwa 22 pogwiritsa ntchito ma voxel ofotokoza zojambula zojambulidwa ndi zithunzi za T1 zolemera za MRI. Kufufuza mapu ochulukirapo owerengetsera ntchito kumagwiritsidwa ntchito poyerekeza kachigawo kakang'ono ka anisotropy (FA) ndi kutanthauza makhalidwe osiyana (MD) komanso imvi (GM) ndi mimba yoyera (WM) pakati pa magulu awa [128]. Zotsatira zimasonyeza kuti maphunziro ovuta kwambiri anali ndi zochepa zochepa za FA ndi MD ndi zochepa zapamwamba komanso zapamwamba kwambiri za GM ndi WM kuposa maulamuliro. Kusintha kwakukulu kwazomwe kunachitika m'madera a ubongo kufunafuna mphotho kufunafuna, kuchepetsa kuletsa, ndi kudya. Kusanthula chigamulochi kunasonyeza kuti FA ndi MD zokhudzana ndi chiwerengero cha GM ndi WM zowonongeka zogwirizana ndi mafuta a thupi. Komanso, mphamvu ya m'mimba yogwiritsira ntchito mafuta yonenepa m'mimba imakhudzidwa kwambiri ndi kuwerengeka kwa GM m'madera ambiri [128].

6.1. Dera-Saliency Dera

Anthu ambiri ovuta kwambiri amasonyeza kuti saganizira za madera ozungulira mphoto, zomwe zimapangitsa kuti munthu adye chakudya chokwanira kuti adzalandire mphotho yokwanira [58,63]. Kugwiritsa ntchito zakudya zokoma kumachititsa malo ambiri a ubongo omwe amavomereza chakudya chokwera chakudya ndipo amachititsa kuti pakhale zakudya zabwino, monga midbrain, insula, dorsal striatum, subcallosal cingulate, ndi PFC. Kukhalitsa kwanthaŵi yaitali kwa zakudya zovuta kumachepetsanso kusasamala komanso zakudya zokondweretsa [92,131]. Dopamine ndi mphuno ya ubongo yomwe imatsutsana kwambiri ndi kukonza mphoto, chilimbikitso, ndi kulimbikitsa khalidwe labwino [31,61], ndipo amachitanso mbali yofunikira pa dera-saliency dera. Masolambic DA kulingalira kuchokera ku ventral tegmental area (VTA) kupita ku NAc imapanga reinforcement for feeding [132,133]. DA atamasulidwa mu dorsal striatum akhoza kuthandizira kuti chakudya chisawonongeke, ndi kukula kwake kwamasulidwe okhudzana ndi chiyeso cha chakudya chosangalatsa [99]. Volkow Et al. [129] PET ndi njira zambiri zowonongeka kuti zitsatire njira za DA zothetsera thanzi labwino, mu nkhani za mankhwala osokoneza bongo, ndi anthu ochepa kwambiri, powonetsa kuti zonse zomwe zimadwalitsa komanso kunenepa kwambiri zimagwiridwa ndi kuchepa kwa DA dopamine 2 (D2) receptor mu statum . Chizoloŵezi chodya nthawi yachisokonezo chinali chosagwirizana kwambiri ndi kupezeka kwa D2 kupezeka mu statum mu nkhani zolemetsa - m'munsimu a D2 receptors, ndipamwamba kwambiri kuti phunzirolo lidye ngati kulimbikitsidwa maganizo [134]. Mu phunziro lina, DA agonist administration yowonjezera kukula kwa gawo la chakudya ndi kutalika kwa kudyetsa, pamene DA yowonjezera nthawi yowonjezerapo yowonjezera thupi ndi mphamvu ya kudya [135]. Mitu yowopsya kwambiri yawonetsetsa mthupi lapamwamba la kagayidwe kake koyambirira kusiyana ndi kawirikawiri pamtundu wa corrox (somatosensory cortex [136]. Iyi ndi malo a ubongo omwe amakhudza mwachindunji ntchito za DA [137,138,139]. Opeza D2 ali ndi ntchito zofunika pakufunafuna malipiro, kuneneratu, kuyembekezera, ndi zifukwa zokhudzana ndi kudya komanso mankhwala ozunguza [140]. Omwe amatsutsa D2 amaletsa makhalidwe ofunafuna chakudya omwe amadalira zakudya zabwino zokhazokha kapena kupititsa patsogolo chiyembekezero cha madalitso [141]. Malingana ndi Stice Et al. [35] anthu angadye kwambiri kuti adzipiritsire mankhwala osokoneza bongo, makamaka omwe ali ndi mavitamini a mtundu wa TaqIA A1 allele) omwe amaganiza kuti alepheretsa chizindikiro cha dopamine m'derali. Potsatira mzere womwewo, chizoloŵezi chodya mopitirira muyezo wolemera omwe ali ndi malingaliro okhumudwa amapezeka kuti akuphatikizana kwambiri ndi ma D2 receptor levels [134]. Wang [142] ndi Haltia [143] adazindikira kuti zolandilira zapansi za D2 zolumikizidwa ndi BMI yokwera kwambiri mopitirira muyeso (BMI> 40) ndi maphunziro onenepa kwambiri, motsatana. Zotsatira izi zikugwirizana ndi lingaliro loti kuchepa kwa ntchito yolandila ya D2 kumalimbikitsa kudyetsa komanso chiopsezo cha kunenepa kwambiri [144]. Guo Et al. [145] anapeza kuti kunenepa kwambiri ndi kudya mwakayakaya kunagwirizanitsidwa ndi D2-like receptor kumanga mphamvu (D2BP) m'mbuyo ndi pamsewu wothandizira, zigawo zazing'ono zomwe zimathandiza kupanga chizolowezi. Mosiyana ndi izi, kugwirizana kolakwika pakati pa kunenepa kwambiri ndi D2BP kunawonetsedwa mu chithunzithunzi cha mphamvu,145].

6.2. Dera Lolimbikitsa-Galimoto

Mbali zingapo za kampani ya prefrontal cortex, kuphatikizapo OFC ndi CG, yakhala ikukhudzidwa ndi cholinga cha zakudya [146]. Zovuta m'madera amenewa zingalimbikitse khalidwe la kudya limene limadalira kukhudzidwa ndi mphotho ndi / kapena zizolowezi za phunziroli. Anthu ovuta kwambiri amasonyeza kuwonjezeka kwa zigawo zapamtunda pamene akudya chakudya [101]. Kuwonjezera apo, amachitanso chidwi ndi zakudya zomwe zimawathandiza kuti azisangalala ndi zofuna zawo [49]. Sucrose imakondweretsanso OFC, dera lomwe limayesa "kuika" phindu la chakudya kapena china chirichonse, makamaka kwa odwala kwambiri poyerekeza ndi kuonda kowonda. Zomwe zimachitika ku OFC, zikutheka kuti zimakhudza njira zopangira malipiro komanso njira zodzilamulira, zingakhale ndi mbali yofunika kwambiri pa matenda ozunguza bongo ndi bulimia nervosa [147]. N'zosadabwitsa kuti machitidwe odyetsa amatha kudya nawo mankhwala ozunguza bwalo la neural ndi mankhwala osokoneza bongo. Mwachitsanzo, Volkow Et al. [148] amalingalira kuti kuwonetsa mankhwala osokoneza bongo kapena mankhwala okhudzana ndi mankhwala mu kuchoka kwadziko kumayambitsanso OFC ndipo kumabweretsa chilolezo chokwanira mankhwala. Chotsatira chomwecho cha OFC chinawonekera mu phunziro lapadera. Umboni winanso umasonyeza mphamvu ya OFC pa zovuta zowonjezereka [149]. Mwachitsanzo, kuwonongeka kwa OFC kumapangitsa munthu kukhala ndi chizoloŵezi cha khalidwe kuti adzalandire mphotho ngakhale pamene sichikulimbikitsanso [149]. Izi zikugwirizana ndi nkhani za osokoneza bongo omwe amanena kuti atayamba kumwa mankhwala sangathe kuimitsa, ngakhale mankhwalawa asakhalanso osangalatsa [98].

6.3. Dera lakumvetsera

Malo, munthu, kapena chidziwitso chingayambitse kukumbukira mankhwala kapena zakudya ndipo zimakhudza kwambiri khalidwe lachilombo, zomwe zimatsimikizira kufunika kwa kuphunzira ndi kukumbukira kuledzera. Kukumbukira kungapangitse chilakolako chachikulu cha mankhwala kapena chakudya (chilakolako) ndipo nthawi zambiri chimabwereranso. Machitidwe ambiri okhudzana ndi malingaliro aperekedwa mu mankhwala osokoneza bongo kapena zakudya, kuphatikizapo maphunziro olimbitsa mtima omwe amathandizidwa (mbali imodzi ndi NAc ndi AMY), kuphunzira chizolowezi (zomwe zimagwirizanitsidwa ndi mbali ndi zilembo za putamen), ndi chikumbutso the HIPP) [150]. Kulimbikitsanso kuphunzira zokhudzana ndi zosakhudzana ndi zochitika zapanda ndale kapena zokopa zowonjezereka mwa kudya kwambiri kumapangitsanso kulimbitsa katundu ndi kulimbitsa mtima ngakhale kuti palibe chakudya. Kupyolera mu kuphunzira kwa chizolowezi, zotsatira zodziwika bwino za makhalidwe zimapangidwa motsogoleredwa pamayendedwe oyenera. Kukumbukira kukumbukira kumaphatikizapo phunzilo la maiko okhudza chiyanjano poyanjana ndi kudya chakudya [149]. Kafukufuku wambiri wa PET, fMRI, ndi MRI apenda kufufuza za ubongo ku chakudya cha zakudya ndi zakudya zomwe zimakhudzana ndi dopamine ntchito ndi ubongo waumphawi molimbana ndi anthu olemera kwambiri ndipo amadziwika zosavomerezeka m'maganizo ndi maulendo okumbukira (mwachitsanzo, AMY ndi HIPP) [98]. Mwachitsanzo, zizindikiro zina zomwe zimapangidwa kuchokera kumalo a homeostatic zimakhala zovuta (mwachitsanzo, kuchedwa kwa fMRI kupopera mpweya mu hypothalamus) pamene zizindikiro za njala kuchokera kumadera okhumudwa / zakumbuyo ndi malo omwe amamvetsera / kumagalimoto (mwachitsanzo, kutsegulira kwambiri ku AMY, HIPP, insula, ndi precentral gyrus poyankha chakudya cues) amakula mwa anthu olemera kwambiri [98]. Ntchito ya Hippocampal yakhala ikuphatikizapo kukumbukira zakudya kapena zotsatira zabwino zodyera anthu ndi makoswe. Ngati ntchitoyi ikudodometsedwa, kukumbukira zochitika ndi zochitika zachilengedwe zingapangitse zowonjezera zokhutiritsa zofunikira pakupeza ndi kudya zakudya [151]. Muzoledzeretsa zokhudzana ndi mankhwala osokoneza bongo, maulendo okumbukira amachititsa chidwi cha zotsatira za mankhwala ndipo motero zimakhudza kuledzeretsa kwa mankhwala osokoneza bongo. Kugwiritsa ntchito zigawo za ubongo zogwirizana ndi kukumbukira zawonetsedwa panthawi ya kumwa mowa mwauchidakwa [152,153] komanso kufuna kukhala ndi mankhwala osokoneza bongo, kanema, kapena kukumbukira [154,155,156]. Kuphunzira kwa chizolowezi kumaphatikizapo kuthamangitsidwa kwa doralum ndi kudumidwa kwa DA m'dera lino [157]. Ogwiritsa ntchito mankhwala osokoneza bongo adachepetsa mawu a D2 receptor ndipo adachepetsa kumasulidwa kwa DA mu dorsal striatum panthawi yosiya [149]. Zinyama, kuwonetsa kwa mankhwala kwa nthawi yaitali kumapangitsa kuti kusintha kosavuta kukhale kosalekeza kuposa zomwe zili mu NAC, zomwe zikutanthawuzidwa kuti ndizopitilira patsogolo muzovuta [158].

6.4. Dongosolo Loletsa Kuletsa

Njira ya ubongo yowonjezera ubongo imapangitsanso malo ozungulira ubongo omwe amagwira ntchito kulamulira, zolinga zoyendetsera zolinga,159]. DlPFC ndi yochepetsetsa gyrus (IFG) ndizo zigawo za dongosolo lomwe likuyendetsedwa kwambiri pamene munthu akuyesetsa khama kuti asinthe chilakolako chawo chodya zakudya zokhazokha koma zakudya zopanda phindu [160]. Ntchito zotero za dlPFC ndi IFG zimapangitsa kuti chilakolako chofuna kudya chiwonongeke, monga zikuwonetseratu kuti zikhale zofunikira kwambiri m'maderawa zomwe zimagwirizana ndi kudziletsa bwino pakusankha pakati pa zakudya zabwino ndi zosafunikira [161]. Anthu ovutika omwe ali ndi PWS, matenda opatsirana pogonana omwe amadziwika kwambiri ndi hyperphagia, amasonyeza ntchito yochepa mu chakudya cha dlPFC pambuyo poyerekeza ndi anthu omwe sali odwala kwambiri [162]. Zonsezi, kuchepetsa kuwononga zakudya za zakudya zikuwoneka kuti zimadalira mphamvu za ubongo zowonongeka kwambiri kuti zisonyeze kufunika kwa chakudya. Kusiyanitsa kwa wina ndi mnzake pazomwe zimadya zakudya zimatha chifukwa cha kusiyana kwa dlPFC ndi / kapena kugwirizana ndi zigawo za chiwerengero cha ubongo [161]. Inde, ngakhale kuti maphunziro olemera kwambiri amasonyeza kuchepetsedwa koyankhidwa mu dlPFC [98], anthu osokoneza bongo adasonyezanso zopanda pake mu PFC, kuphatikizapo a CG anterior [163]. PFC ikuthandizira kupanga chisankho komanso kuteteza malamulo [164]. Kusokonezeka kwa PFC kungapangitse kusankha zosayenera zomwe zimapangitsa kuti phindu likhalepo panthawi yochedwa koma mayankho ogwira mtima. Zingathandizenso kulepheretsa kugwiritsira ntchito mankhwala osokoneza bongo mosasamala kanthu za chilakolako cha chizolowezi choletsa kumwa mankhwala [163]. Motero, kulephera kwa kudziwonetsera nokha ndi njira zopangira zisankho mukumwa mankhwala osokoneza bongo [165,166] mwachiwonekere amagwirizanitsidwa ndi kusokoneza ntchito zapamwamba. Pochirikiza lingaliro limeneli, kufufuza kwapadera kunasonyeza kuwonjezeka kwakukulu kwa nthambi ya dendritic ndi kuchulukanso kwa mitsempha yotchedwa dendritic spines mu PFC yotsatira kayendedwe ka cocaine kapena amphetamine [167]. Kusintha kwa mgwirizano wa synaptic kungapangitse kupanga zosankha zopanda chilungamo, chiweruzo, ndi chidziwitso chakumudziwa mowa mankhwala osokoneza bongo. Kusintha kwamtundu umenewu pa oprontal activation kumachitika panthawi yomwe akugwira ntchito yosunga fodya poyerekeza ndi omwe amasuta fodya [168]. Pankhaniyi, Goldstein Et al. [163] kale adanena kuti kusokonezeka kwa PFC kungayambitse kuwonongeka kwa khalidwe lodzikonda / lodziletsa pofuna kukhala ndi khalidwe lodzidzimutsa. Kwenikweni, kumwa mowa mwauchidakwa kungapangitse khalidwe losautsa chifukwa cha kuwonongeka kwa chiletso choletsedwa kuti kortteal cortex ikhale yoposa AMY [169]. Kusokoneza mphamvu yapamwamba yolamulira kumamasula makhalidwe omwe nthawi zambiri amawunika mosamala ndipo amachititsa kuti anthu asamapanikizidwe komanso kuti khalidwe lopangika likhale lothandiza [163].

7.1. Zakudya ndi Zamoyo

Zakudya ndi zamoyo zomwe zimayambitsa kuchepetsa mphamvu zowonjezera mphamvu ndi kuonjezera ndalama zowonjezera mphamvu pogwiritsa ntchito pulogalamu yoyenera ndi zochita masewera olimbitsa thupi ndizofunikira pa mapulogalamu onse oyang'anira zolemera [170]. Zakudya zimachokera ku mfundo za kagayidwe kake komanso kugwira ntchito mwa kuchepetsa kudya kwa mphamvu (mphamvu) kuti zisawononge mphamvu (mwachitsanzo, mphamvu zambiri zimagwiritsidwa ntchito kuposa momwe zimagwiritsidwira ntchito). Mapulogalamu odyetsa zakudya amatha kuchepetsa kulemera kwa nthawi yochepa [171,172], koma kukhala ndi kulemera kwa thupi nthawi zambiri kumakhala kovuta ndipo kawirikawiri kumafuna kuchita masewera olimbitsa thupi ndi zakudya zochepa zomwe zimakhala gawo losatha la moyo wa munthu [173]. Kuchita masewera olimbitsa thupi ndi gawo lalikulu la pulogalamu yolemetsa, makamaka kulemera kwa thupi. Pogwiritsa ntchito, minofu imagwiritsa ntchito mphamvu zochokera ku mafuta ndi glycogen. Chifukwa cha kukula kwake kwa minofu ya mwendo, kuyenda, kuthamanga, ndi njinga zamoto ndi njira zothandiza kwambiri zolimbitsira thupi kuti kuchepetsa mafuta [174]. Kuchita masewera olimbitsa thupi kumakhudza kuchuluka kwa mphamvu. Pochita maseŵera olimbitsa thupi, mofanana ndi kuyenda kofulumira, pali kusintha kosagwiritsidwa ntchito kwambiri kwa mafuta monga mafuta [175,176]. American Heart Association imalimbikitsa osachepera 30 min zochita masewera olimbitsa thupi masiku osachepera asanu pa sabata kuti akhale ndi thanzi labwino [177]. Monga momwe amachitira ndi madokotala, madokotala ambiri alibe nthawi kapena luso lolangiza odwala pulogalamu yochita zolimbitsa thupi zomwe zimagwirizana ndi zosowa zawo. Kugwirizana kwa Cochrane kunapeza kuti zochitika zokha zinkatsogolera kulemera kochepa. Kuphatikiza ndi zakudya, komabe, zinapangitsa kuti 1 kulemera kwa kilogalamu yakulepheretsa kudya zakudya zokha. Chilogalamu ya 1.5 (3.3 lb) kutayika kunayesedwa ndi kuchita masewera olimbitsa thupi [178,179]. Mavuto a moyo wautali wautali wosamalira ndi kusintha kwa moyo ndi otsika, kuyambira 2% mpaka 20% [180]. Zakudya ndi zamoyo zimasintha zimathandiza kuchepetsa kupweteka kwambiri pathupi ndikumapangitsa zotsatira za amayi ndi mwana [181]. Kukhalitsa miyoyo kumakhalabe mwala wapangodya wodwala kwambiri, koma kutsatira ndizopambana komanso zomwe zimapindulitsa kwa nthawi yaitali chifukwa cha zolepheretsa zomwe anthu omwe akukhudzidwa ndi odwala omwe amachiza chithandizo amakhala nacho.

7.2. Mankhwala Osokoneza Bongo

Pakalipano, mankhwala anayi ochepetsa kulemera kwavomerezedwa ndi US Food and Drug Association (FDA): Xenical, Contrave, Qsymia, ndi Lorcaserin [4]. Mankhwalawa agawanika kukhala mitundu iwiri. Xenical ndiyo yokha mafuta omwe amatenga inhibitor. Xenical amachita ngati lipase inhibitor, yomwe imachepetsa kuyamwa kwa mafuta kuchokera ku chakudya cha anthu ndi 30%. Cholinga chake chimagwiritsidwa ntchito pamodzi ndi wothandizira zaumoyo - machitidwe oyang'aniridwa a caloric restriction [182].

Mtundu wina, womwe umaphatikizapo mankhwala ena atatu, amachititsa kuti CNS ikhale "chilakolako chofuna kudya." Mwachitsanzo, mankhwala osokoneza bongo (2012) omwe amagwiritsidwa ntchito (5), amagwiritsa ntchito mankhwala osokoneza bongo amodzi a 2HTXNUMXC receptor. Iwo unakhazikitsidwa molingana ndi katundu wa anorexicic wa receptor kuti athetsere kutaya kwa thupi [183]. Kugwiritsa ntchito mapulogalamu a 5HT2C mu hypothalamus amachititsa kupanga pro-opiomelanocortin (POMC) kupanga ndi kulimbikitsa kugonana. Munthu wina wa 5-HT2C amalandira chilakolako cha chilakolako kudzera mu serotonin system [54]. Kugwiritsira ntchito Lorcaserin kumagwirizanitsidwa ndi kulemera kwakukulu kwabwino komanso kuwonetsetsa bwino kwa m'mimba mwa odwala omwe ali ndi mtundu wa 2 shuga [183]. Mankhwala ena awiri, Contrave ndi Quexa, akuwongolera madalitso a DA. Kusiyanitsa ndi kuphatikizapo mankhwala awiri ovomerezeka-bupropion ndi naltrexone. Chidakwa chokha chimapangitsa kuti thupi likhale lochepa kwambiri, pamene kuphatikiza kuli ndi mphamvu [184]. Qsymia (Quexa) ili ndi mankhwala awiri a mankhwala, phentermine ndi topiramate. Phentermine yayigwiritsidwa ntchito bwino kwa zaka kuti achepetse kunenepa kwambiri. Topiramate wakhala ikugwiritsidwa ntchito ngati anti-convulsant mu odwala matenda a khunyu, koma inachititsa kuti thupi liwonongeke anthu ngati zotsatira zovulaza [54]. Qsymia imaletsa chilakolako pakupanga anthu kumverera. Malowa ndi othandiza makamaka kwa odwala kwambiri chifukwa amalepheretsa kudya kwambiri ndikulimbikitsana kutsatira ndondomeko yodyera.

7.3. Bariatric Surgery

Odwala ena olemera akhoza kupindula ndi mankhwala olemera omwe amalephera kugwira ntchito, koma nthawi zambiri amadwala. Kuchita opaleshoni yapamwamba (kugwiritsidwa ntchito kosakanikirana ndi abambo (AGB), Roux-en Y m'mimba mwachisawawa (RYGB), kapena laparoscopic manyolo opangira (LSG)) [185] amaimira njira yokhayo yamakono yowonetsera kwambiri kunenepa kwambiri ndi kukhazikitsidwa kwa nthawi yaitali [186]. Kuchita opaleshoni ya bariatri kumasintha maonekedwe a mahomoni ndi ma neural. Kumvetsetsa njira zomwe zimayambitsa matenda opatsirana pogonana ndi kusintha kwa matenda ndi opaleshoni zidzapititsa patsogolo chithandizo chopanda opaleshoni kuti athetse kunenepa ndi zowonjezereka, zomwe zingakhale njira yabwino kwa anthu ovutika kwambiri omwe alibe mwayi kapena osayenera kuchitidwa opaleshoni. RYGB ndi ndondomeko ya bariatric yomwe imachitika kawirikawiri, yopereka zofunikira zazikulu ndi zolemetsa zowonjezereka pakutsata nthawi yayitali [187]. Komabe, njira zothandizira mu RYGB zomwe zimabweretsa kulemera kwa thupi sizikumveka bwino. Zambiri mwa zomwe zimachititsa kuchepa kwa caloric sizodziwika ndi njira zowonongeka komanso zogwiritsira ntchito malaria ndipo zimalingaliridwa kuti zimagwirizanitsidwa ndi ntchito ya neuroendocrine [188]. RYGB imaganiziridwa kuti imachititsa kusintha kwakukulu ndi panthawi imodzi m'matumbo a mapeptidi [95,189], kuyambitsa ubongo [95,190] chilakolako chodya [190], ndi zokonda zosangalatsa. Mwachitsanzo, kuchepetsa kuperewera kwa ghrelin ndi kale komanso kumbuyo kwa PYY ndi GLP-1 kungachepetse njala ndi kulimbikitsana [191]. Malinga ndi kusintha kwa matenda a peptide, pang'ono pokha amadziwika za kusintha kwa ubongo pambuyo pa njira za graatric. Kafukufuku wothandizira kuchepetsa kuperewera kwa pulogalamu ya opaleshoni yowonjezera kuwonjezeka kwa zokhudzana ndi mphoto / hedonic kuchitapo kanthu potsutsa zilakolako zamagetsi [95], zomwe zimathandiza kufotokoza kulemera kwatsopano. Mosiyana ndi zimenezi, kusowa kwa chilakolako chofuna kudya pambuyo pa RYGB, ngakhale pakupeza chakudya chokoma kwambiri, kumakhala kochititsa chidwi, ndipo kumagwirizana ndi kusintha kwasinthidwe m'mayendedwe a mayendedwe a zakudya. Ochner Et al. [188] amagwiritsira ntchito fMRI ndi miyeso yolemba mawu kuti awonetse ubongo wotsegulira ndi kufuna kudya chifukwa cha zakudya zakutali ndi zakutsika kwa odwala azimayi a 10, mwezi umodzi komanso opaleshoni ya RYGB. Zotsatirazo zinawonetsa kuchepetsa mphulupulu mu ubongo wa ubongo m'madera ofunika mu njira yopatsa mphoto [188]. Panalinso kuchepa kwakukulu kochitidwa mwachipatala kwa mwamuna kapena mkazi (zooneka bwino) zomwe zimagwiritsidwa ntchito pamtima chifukwa cha zakudya zakutchire kusiyana ndi zakudya zakutchire, makamaka m'madera omwe mumapezeka njira yochepetsera ululu kuphatikizapo VTA, ventral striatum , kuika, kutsekemera, ndi kutsekemera kwapadera (dmPFC) [188]. Izi ndi zosiyana ndi mayankho a chakudya chokwanira kumalo otsika kwambiri a caloric m'madera monga gyrus, thalamus, lentiform nucleus ndi caudate, ACC, gyrus yeniyeni, gyrus yapamwamba, gyrus yapansi, ndi gyrus yapakati pamaso opaleshoni [188]. Kusintha kumeneku kunawonetseratu kuchepa kwa nsomba zamakono zofuna kudya, zomwe zinali zogwirizana ndi chakudya chomwe chinali ndi mphamvu ya caloric (p = 0.007). Zochitika zokhudzana ndi opaleshoni za RYGB zimapereka njira yothetsera kuchepetsa zosankha za zakudya zamakono, ndikupatsanso chisankho chotsatira cha kusintha kwa caloric pakapita opaleshoni [185,188]. Kusintha kumeneku kungakhale mbali imodzi yogwirizana kwambiri ndi lingaliro losinthidwa la mphoto [192]. Halmi Et al. [193] tawonetsa kuti chiwerengero chochepa chimachepetseka kudya zakudya zamtundu wapatali komanso zakudya zamtundu wa calories miyezi isanu ndi umodzi mutatha kudya chapamimba. Odwala adapeza kuti zakudya izi sizinali zosangalatsa. Ena kudutsa odwala ngakhale kupeŵa zakudya zamtengo wapatali [194], pamene ena sanasangalale ndi maswiti kapena masitala opita opaleshoni [195,196,197,198]. Pewani m'malo mwa kukoma kwa zakudya, monga kuvomereza kosavuta kapena kupsya mtima, zafotokozedwa pambuyo pa opaleshoni ya bariatric [192,199]. Komanso, kusintha kwa ubongo wa dopamine kunawonekera pambuyo pa opaleshoni ya bariatric. Pamene amalonda a D2 adachepetsedwa mu thalamus, epalatigra, thalamus, HPAL, substantianigra, medial HPAL, ndi AMY pambuyo pa RYGB ndi kuperewera kwa manja, kuwonjezeka kwa obvomerezeka a D2 kunapezeka mu ventral striatum, caudate, ndi putamen yomwe inali yofanana ndi kulemera kwa thupi [131,200,201]. Kusiyanitsa mu zotsatira kungakhale chifukwa cha kukhalapo kwa zinthu zovuta zomwe zingasinthe dopamine chizindikiro [192]. Pafupipafupi, opaleshoni yowonjezereka, makamaka njira ya RYGB, ndiyo njira yabwino kwambiri yothetsera kunenepa kwambiri komanso kukhudzidwa kwake. Kufufuzanso kwina kuli kofunikira kuti tiyang'ane momwe matumbo-ubongo umagwirizanitsa zotsatira zodabwitsa za opaleshoni pa kuyang'anira njira yopezera mphoto [202].

7.4. Fecal Microbiota Kufalitsa

Umboni wokhala pamwamba umasonyeza kuoneka kwa mphamvu ya mtumbo wa tizilombo poyendetsa mphamvu zamagetsi ndi kuchepetsa kulemera kwa nyama ndi anthu. Ntchito yotereyi imakhudza chitukuko ndi kukula kwa kunenepa kwambiri ndi matenda ena a shuga kuphatikizapo mtundu wa 2 shuga. Kugwiritsidwa ntchito m'matumbo tizilombo toyambitsa matenda kumaimira njira yatsopano yoperekera kunenepa kwambiri kuposa zakudya ndi machitidwe olimbitsa thupi [203]. Njira yatsopano yothandizira, kufalikira kwa fecal microbiota (FMT), posachedwapa yatulukira kuchipatala cha kunenepa kwambiri [204]. Matumbo a microbiotas amagwiritsa ntchito zakudya zowonjezereka m'magetsi olemera omwe amagwiritsidwa ntchito ndi ogwira ntchito pamodzi ndi zomera za commensal [203,204] ndikumasintha kagwiritsidwe ntchito kamene kamagwiritsa ntchito kupezeka kwa zakudya. Pambuyo poyerekeza ndi mbiri ya distal gut microbiota ya mavitamini ovuta kwambiri ndi mavitenda awo owonda, ndi a anthu olemera kwambiri komanso odzipereka, adapeza kuti kunenepa kwambiri kumasiyana ndi kuchuluka kwa mabakiteriya akuluakulu, Bacteroidetes ndi Firmicutes. Zomwe zimachitika m'maganizo ndi m'thupi zimapangitsa kumvetsetsa mphamvu za mabakiteriyawa pamtundu wa makoswe wa microbiota. Mwachindunji, tizilombo toyambitsa matendawa timakhala ndi mphamvu yowonjezera yowonjezera mphamvu kuchokera ku zakudya. Kuwonjezera pamenepo, khalidweli ndilolumikiza: chiwonongeko cha mbewa zopanda majeremusi ndi "zowonongeka kwambiri" zimakhala ndi mafuta ochulukitsa thupi lonse kuposa chikoloni ndi "wodwala". Zotsatirazi zimasonyeza kuti tizilombo toyambitsa matenda ndizofunika kwambiri kuti tizilombo toyambitsa matenda tizilombo toyambitsa matenda [203,205]. Zoonadi, kafukufuku wina anafotokoza kuti 60% yowonjezera mafuta a thupi, insulini kukana, komanso kutsekula kwa phenotype kovuta kwambiri pambuyo poyambitsa matumbo a tizilombo toyambitsa matenda kuchokera m'mimba yomwe imatulutsira mbewa kupita ku mbewa [206]. Deta pankhaniyi ndi yochepa kwambiri mpaka pano. Chimodzimodzinso, choyesedwa choyesedwa chinachititsa amuna a 18 omwe ali ndi matenda amadzimadzi kuti agwire FMT. Iwo anapatsidwa mwina zofunda zawo kapena ndowe zoperekedwa kuchokera kwa amuna oonda [207]. Amuna asanu ndi anayi omwe analandira chitsime kuchokera kwa operekera odwala adayamba kuchepetsa kuchepetsa kudya kwa triglyceride komanso kuwonjezereka kwa pulogalamu ya insulini yokhudzidwa poyerekeza ndi omwe anaikidwa ndi chovala chawo (placebo)207].

Ntchitoyi imathandizidwa ndi National Natural Science Foundation ku China pansi pa Grant Nos. 81470816, 81271549, 61431013, 61131003, 81120108005, 31270812; Project for National Key Research and Development Program (973) pansi pa Grant No. 2011CB707700; ndi Zokambirana Zowona Zophunzira za Zigauni Zonse zapakati.