Neural Correlates ea Khatello ea Kelellano le Lijo tsa Lijo-Ho Khahloa ke Lijo Tse Matla ka Botenya (2013)

. 2013 Feb; 36 (2): 394-402.

E hatisitsoe Inthaneteng 2013 Jan 17. doi:  10.2337 / dc12-1112

PMCID: PMC3554293

Kopano le maemo a insulin

Ania M. Jastreboff, MD, PHD,1,2 Rajita Sinha, PHD,3,4,5 Cheryl Lacadie, BS,6 Dana M. Nyane, PHD,3,7 Robert S. Sherwin, MD,1 'me Marc N. Potenza, MD, PHD3,4,5

inahaneloang

LEHLOHONOLO

Ho nona ho amana le liphetoho tse teng libakeng tsa boko ba corticolimbic-striatal tse kenyelletsang molemong oa lijo le moputso. Matšoenyeho le ho ba teng ha mekhoa ea lijo e ka khothatsa e mong le e mong ho ja le ho etsa corticolimibic-striatal neurocircuitry. Ha ho tsejoe hore na lintlha tsena li sebelisana joang ho susumetsa likarabo tsa boko le hore na litšebelisano tsena li susumetsoa ke botenya, maemo a insulin, le kutloisiso ea insulin. Re ile ra nahana hore batho ba batenya ba ka bonts'a likarabo tse kholo ho corticolimbic-striatal neurocircuitry kamora ho pepesetsoa khatello ea maikutlo le lintho tse amanang le lijo le hore ts'ebetso ea ts'ebetso ea boko e ka lumellana le litakatso tsa lijo tse fumanehang, maemo a insulin, le HOMA-IR.

MORERO OA HO FUMANA LE LITLHAHISO

Ho ile ha hlahlojoa maemo a insulin a potlakileng lithutong tse tala le tse bobebe tse ileng tsa pepesetsoa khatello ea maikutlo le litheko tsa lijo tse ratoang haholo nakong ea ts'ebetso ea MRI.

LIPOTSO

Obese, empa eseng leeme, batho ka bomong ba bonts'itse ts'ebetso e eketsang ts'ebetsong libakeng tse bataletseng, tse kenang kahare le tse tšabehang nakong ea ho pepesehela lijo tse ratoang haholo le khatello ea maikutlo. Ho batho ba batenya empa ba sa thekesele, litakatso tsa lijo, insulin le HOMA-IR li ile tsa hokahana hantle le tšebetso ea neural libakeng tsa boko ba corticolimbic-striatal nakong ea lijo tseo motho a li ratang haholo le tse hlokang khatello. Kamano lipakeng tsa insulin le ho lakatsa lijo ho batho ba batenya ho feta tekano li ile tsa hokahanngoa ke mesebetsi libakeng tse fanang ka meputso ho kenyelletsa striatum, insula le thalamus.

CONCLUSIONS

Liphumano tsena li bonts'a hore batho ba batenya, empa ha ba thekesele, batho ba bonts'a ts'ebetso ea corticolimbic-striatal ha ba araba lijo tseo ba li ratang haholo le khatello ea maikutlo le hore likarabo tsena tsa boko li hokahanya kamano lipakeng tsa HOMA-IR le takatso ea lijo. Ho ntlafatsa kutloisiso ea insulin le ho fokotsa ho kenella hape ha corticolimbic-striatal ho litekanyetso tsa lijo le khatello ea maikutlo ho ka fokotsa takatso ea lijo le ho ama boits'oaro ba ho ja ka botena.

Ho Nona Bothata ke bothata ba bophelo bo botle ba sechaba bo khethollang batho ba fetang limilione tse 500 lefatšeng ka bophara () maemong a sa foleng a bongaka a mofuta oa lefu la tsoekere la 2 le lefu la pelo (). Karolo ea ts'ebetso ea methapo e kholo ea botoneng e ntse e hlahlojoa ka thuso ea mekhoa e tsoetseng pele ea neuroimaging e etsang hore ho hlahlojoe tšebetso ea boko ba motho (,). Litekanyetso tsa lijo le khatello ea maikutlo, lintlha tse peli tsa tikoloho tse amang boits'oaro ba ho ja (,), fana ka maikutlo a fapaneng (,-) le likarabo tsa neural (-) ka tse bateng ha li bapisoa le batho ba makhethe. Liphetoho tsena tsa neural li kenyelletsa empa ha li felle feela ho striatum (), sebopeho se kenelletseng ts'ebetsong ea ts'usumetso ea meputso le karabelo ea khatello ea maikutlo (), le insula, e kenyelletsoang ho hlokeng le ho kopanya maikutlo, joalo ka tatso (), ka hare ho mmele () mabapi le mekhoa ea lijo (,,) le liketsahalo tse sithabetsang (). Ho khothalelitsoe hore liphapang libakeng tsena tsa neural ho batho ba batenya haholo () e ka amahanngoa le takatso e matla ea lijo () le boits'oaro bo bobe ba ho ja (), mohlomong e amang khetho ea lijo le tšebeliso (,,). Kahoo, ho kena lipakeng tsa botena ba botšehali ho ka tsamaisoa ke ho fumana kutlwisiso e nepahetseng ea hore na lintlha tse ling tse amanang le botenya (mohlala, lihormone le metabolic) li ka amana joang le methapo e ka tlase ea khatello ea maikutlo le likarabo tsa tlhahlobo ea lijo le hore na liphapang tsena li ka ama lijo joang- ho batla lintho tse u susumetsang tse kang ho lakatsa lijo.

Lipontšo tsa Hormonal le lintlha tsa metabolic li laola homeostasis ea matla ka liketso tsa ho potoloha le tse bohareng (). Boemong ba ho ba le botenya, ho fetoha hangata maemong a insulin le kutloisiso ea insulin hangata ho etsahala () hape e ka ntšetsa pele physiology le boits'oaro bo fosahetseng (). Ho fanoe ka maikutlo a hore ho hanyetsa insulin e bohareng e ka ba karolo ea bohlokoa e tlatsetsang mohopolong o fetotsoeng oa lijo le liphetoho litseleng tsa khothatso (moputso)). Ka sebele, li-insulin tsa li-insulin li hlahisoa libakeng tsa homeostatic tsa bongo, joalo ka hypothalamus (), hammoho le libaka tse khothatsang tsa moputso tse hokahantsoeng le boits'oaro bo amanang le lijo bo kenyeletsa sebaka sa tefo ea sepheo sa phallo (VTA) le substantia nigra (SN) (), likarolo tse peli tse fetisang lipontšo ka "dopaminergic neurons" ho ea sebakeng sa cortical, limbic, le striatal brain (). Pono ena e tšehetsoa hape ke lithuto lithutong ka bobeli le bathong. Neuron e khethehileng ea insulin receptor knockout litoeba li holisa hyperinsulinemia le ho hanyetsa insulin hammoho le botenya bo khothalletsoang ke ho ja (). Ho batho, matla a khokahano ea khokahano ea "state-network" ho putamen le orbitofrontal cortex (OFC) ho tlalehiloe hore a lumellana hantle le litekanyetso tsa insulin tsa ho itima lijo le hampe ka ho hloka matla ha insulin (), le bokhoni ba insulin ba ho eketsa ho ts'oaroa ha tsoekere ka har'a "ventral striatum" le "cortex" ea pele bo ile ba bonoa hore bo fokotsehile lithutong tse hananang le insulin (). Ntle le moo, ho araba litšoantšo tsa lijo, batho ba batenya ba nang le lefu la tsoekere la 2 ba bontšitse ts'ebetso e eketsehileng ts'ebetsong, OFC, le striatum ha ba bapisoa le batho ba se nang lefu la tsoekere la 2 (). Litlamorao ho boetse ho hlokometsoe lipakeng tsa ho latela kalafo ea lijo le ho latela ts'ebetso ea ts'ebetso le ts'ebetso ho ts'ebetso ea kelello le OFC le lipakeng tsa ho ja maikutlong le ts'ebetsong ho amygdala, caudate, putamen, le li-bokellase tsa nucleus ().

Leha ho le joalo, ha ho tsejoe hore na phapang pakeng tsa maemo a insulin le kutloisiso ea insulin li ama likarabo tse ikhethang tsa boko ba motho nakong ea ho pepesetsoa lintho tse atisang ho hlaha tse kang litloaelo tsa lijo le liketsahalo tse sithabetsang le hore na likarabo tse joalo tsa neural li ka susumetsa litakatso tsa lijo tse ka hlahisang boitšoaro ba ho ja. Re ts'elisitse hore liemahale tse feteletseng, empa li sa thekesele, batho ka bomong ba ne ba tla hlahisa likarabo tse matla tsa neural ho li-neurocircuits tse khothatsang tse akaretsang maikutlo a kopanyang le ho ikopanya hoa motho ka mong-tlhahlobo-lipuisano (cortical), maikutlo-memori (limbic), le ts'ebetso ea moputso (striatal) nakong ea tataiso e khutšoane Ho pepesehela litšebeletso tsa lijo tse u li ratang haholo, khatello ea maikutlo le ho se phomole; hore likarabo tsena tsa neural li ne li tla lumellana le litakatso tsa lijo le maemo a insulin le khanyetso ea insulin (joalo ka tlhahlobo ea tlhahlobo ea homeostasis ea ho hanyetsa insulin [HOMA-IR]); le hore kamano lipakeng tsa ho hanyetsa insulin le takatso ea lijo e tla kenelloa ke ts'ebetso ea boko ea tikoloho.

MORERO OA HO FUMANA LE LITLHAHISO

Banna le basali, pakeng tsa lilemo tsa 19 le 50 lilemo, ka BMI ≥30.0 kg / m2 (sehlopha se feta) kapa 18.5-24.9 kg / m2 (sehlopha se otlolohileng), bao ka tsela e 'ngoe ba neng ba phela hantle ba ile ba hiroa ka papatso ea lehae. Mekhoa ea ho qheleloa ka thoko e kenyelelitse maemo a sa foleng a bongaka, mafu a kelello (litekanyetso tsa DSM-IV), likotsi tsa methapo ea pelo kapa mafu, ho noa meriana efe kapa efe ea ngaka, IQ <90, ho nona haholo (25.0-BMI-29.9 kg / m2), ho sitoa ho bala le ho ngola ka Senyesemane, boimana, le claustrophobia kapa tšepe e tsamaellanang le mohopolo oa matla a kelello (MRI). Boithuto bona bo amohetsoe ke Komiti ea Patlisiso ea Botho ea Yale. Lithuto tsohle li fane ka tumello e saenneng e fanoeng.

Teko ea biochemical

Ka letsatsi la tlhahlobo pele ho seboka se sebetsang sa MRI (fMRI), disampole tsa mali bakeng sa tekanyo ea li-insulin tse potlakileng tsa insulin le tsoekere li fumanoe ho 8: 15 am mme e bolokiloe ho −80 ° C. Glucose (glucose e potlakileng ea plasma glucose [FPG] e ile ea lekanyetsoa ho sebelisoa Delta Science Science glucose reagent (Henry Schein) le insulin e sebelisang radioimmunoassay (Millipore [eo pele e neng e le Linco]) ea mehleng. Mohlala ka mong o ne o etsoa habeli bakeng sa netefatso. HOMA-IR e ile ea baloa ka tsela e latelang: [glucose (mg / dL) × insulin (μU / mL)] / 405. Neuroimaging e ile ea etsoa matsatsing a 7 ka mor'a ho fumana data ea laboratori.

Ntshetsopele ea mangolo a litšoantšo

Pele ho seboka sa motho ka mong sa fMRI, lingoloa tse tataisitsoeng bakeng sa lijo tse ratoang, khatello ea maikutlo le maemo a ho se nke lehlakore li ile tsa qaptjoa ho sebelisoa mekhoa e neng e thehiloe pele (). Lingoloa tse etselitsoeng motho ka mong li hlahisitsoe hobane liketsahalo tsa motho li baka ho ikatisa 'meleng hape li hlahisa maikutlo a tebileng ho feta setšoantšo sa maemo a sa amaneng le maemo (). (Bona Tlatsetso ea Tlatsetso 'me Letlapa le tlatsetsang 7 bakeng sa mehlala ea lijo tse kenyellelitsoeng litulong tse ratoang haholo tsa lijo le mohlala oa sengoloa sa thatohatsi ea lijo, hammoho le lisebelisoa tse tlatsetsang ho Jastreboff et al. [bakeng sa khatello ea baemeli le mangolo a khathollang a khathollang.)

seboka sa fMRI

Barupeluoa ba hlahisitsoeng bakeng sa ho nahana ka thapama ho 1: 00 pm kapa 2: 30 pm le litaelo tsa hore ba jele ~ 2 h pele ho seboka sa ho hlahloba hore ba ne ba sa lapa haholo kapa ba tletse. Re ile ra lekola litekanyetso tsa tlala e pele le ka mor'a linako tsa ho hlahlobisisa; ha ho na phapang ea lipalo pakeng tsa mekhoa ea lihlopha tsena tse peli [t(46) = 1.15, P > 0.1]. Morupeluoa e mong le e mong o ile a amoheloa ka phapusing ea liteko ho likarolo tse itseng tsa mekhoa ea ho ithuta ea fMRI. Lihlooho li ne li behiloe ho skena sa MRI mme li etsoa fMRI nakong ea seboka sa 90-min. Ka tatellano e sa lekanyetsoang ea li-counter, ba ile ba pepesetsoa lijo tseo ba li ratang ka ho fetesisa, khatello ea maikutlo le maemo a khathollang a litšoantšo. Liteko tse tšeletseng tsa fMRI (tse peli ka boemo bo le bong) li fumanoe ho sebelisoa sebopeho se nang le 5.5 min. Teko e 'ngoe le e' ngoe e ne e kenyelletsa nako ea khutso ea 1.5-min e lateloang ke nako ea litšoantšo tsa 2.5-min (ho kenyeletsoa 2 min ho nahana pale ea bona e ikhethang ha e ntse e bapaloa ho bona ho tsoa ho rekoto ea audio e kileng ea etsoa le 0.5 min ea nako ea litšoantšo tse khutsitseng nakong eo o ile a tsoela pele ho nahana pale ha a ntse a khutsitse) le nako ea phomolo e khutsitseng ea 1-min.

Netefatso ea paradigm e tataisitsoeng ea litšoantšo

Ho lekola likarabo tse lumellanang le maemo a setšoantšo sa khatello ea maikutlo, litekanyetso tsa matšoenyeho li ile tsa fumanoa ho tsoa lithutong pele le ka mor'a mongolo o mong le o mong oa litšoantšo. Ho lekola matšoenyeho, barupeluoa ba ile ba botsoa joalo ka pele () ho lekanya hore na ba tsitsipane hakae, ba tšoenyehile kapa / kapa jittery ba ikutloa ba sebelisa sekhahla sa lintlha tsa Likert 10 pele le kamora teko ka 'ngoe ea fMRI. Lithutong tse batang le tse monate, litekanyetso tsa ho tšoenyeha li ile tsa eketseha kamora boemo ba khatello ea maikutlo [ F(1.96) = 7.11, P <0.0001; otlolohile: F(1.96) = 6.94, P <0.0001]. Ho ne ho se na phapang lipalo tsa matšoenyeho lipakeng tsa lihlopha qalong [F(1.48) = 0.13, P = 0.72] kapa ka mor'a setšoantšo [F(1.48) = 0.23, P = 0.64]. Ntle le moo, litekanyetso tse hlakileng tsa ho hlakileng li ile tsa fumanoa moo lithuto li neng li bontša kamoo ba neng ba khona ho bona pale ea bona ka bonngoe ha ba ntse ba inthaneteng. Ho ne ho se na phapano lipakeng tsa sehlopha sa litekanyetso tsa ho hlaka ha litšoantšo [t(4) = 1.3, P = 0.26].

fMRI phihlello le tlhaiso-leseling ea lipalo

Litšoantšo li fumanoe Yale Magnetic Resonance Research Center e sebelisang 3-Tesla Nokia Trio MRI sistimi e nang le mochini oa li-coil o tloaelehileng oa quadrature, o sebelisa T2 * -sensitive gradient-hopolo e le 'ngoe e thuntsoeng e le' ngoe ea echo-planar pulse. Bona Tlatsetso ea Tlatsetso bakeng sa lintlha tse ling tsa ho fumanwa le ho hlahlojoa ha fMRI. Bakeng sa lipalo-palo tse hlalosang, liphapang tse pakeng tsa sehlopha ka mehato e ikhethileng le ea bongaka li ile tsa lekoa li sebelisoa t tlhatlhobo, Fisher hantle, le χ2 liteko. Re sebelisitse li-macro tsa SPSS tse nang le 10,000 bootstrap ho lekanya mefuta ea poelano ().

LIPOTSO

Lipalo-palo tsa sehlopha le litekanyetso tsa metabolism tsa ho itima lijo

Baithaopi ba phetseng hantle ba mashome a mahlano ba nang le bophelo bo botle le baithaopi ba ne ba tšoantšoa ka ho lekana ho latela lilemo (ho bolela lilemo tsa 26), bong (38% basali), morabe (68% Caucasian), le thuto (Letlapa le tlatsetsang 1). Sehlopha sa batenya (N = 25) e ne e na le moelelo ± SD BMI ea 32.6 ± 2.2 kg / m2, le sehlopha se setle (N = 25) e ne e na le BMI e bolelang 22.9 ± 1.5 kg / m2. Leha ho se lithuto tse fumanoeng tse nang le lefu la tsoekere, lithuto tse khahlileng le tse hloahloa li ne li fapane mabapi le khanyetso ea insulin joalokaha ho lekiloe ke HOMA-IR [sehlopha sa obese se bolela 3.8 ± 1.4 le sehlopha se setle sa 2.5 ± 1.0, t(41) = −3.42, P = 0.0013] le litekanyetso tsa insulin tsa ho itima lijo [sehlopha se feteletseng sa 16.3 ± 5.8 μU / mL le lean 11.1 ± 3.7 μU / mL, t(33.7) = −3.53, P = 0.0012]. Maemo a FPG a ne a sa fapana lipakeng tsa lihlopha [t(41) = −1.34, P = 0.19] (Letlapa le tlatsetsang 1).

Limapa tse fapaneng le 'mele oa hau: Batho ba batenya ba bonts'a likarabo tse ngata tse tsoang likarolong tse fapa-fapaneng tsa corticolimbic

Joalokaha ho ne ho ka lebelloa, lihlopha tse mabothobotho le tse natefileng li bonts'itse ts'ebetso ea libaka tse nang le corticolimbic-striatal ho arabela khatello ea maikutlo le maemo a ratoang a ho ja lijo le ts'ebetso e matla feela ea ts'ebetso nakong ea ho phomola (P <0.01, phoso e amanang le lelapa [FWE] e lokisitsoe (Tlhahiso e eketsehileng Fig. 1). Ho fapana le limmapa tsa ts'ebetso ea neural activation e tona le ea lithuto tse bobebe, ho ne ho se na phapano lipakeng tsa sehlopha ka lebaka la ts'ebetso e arabang boemo ba ho se kopanele. Kahoo, boemo ba phomolo bo sa nke lehlakore bo sebelisitsoe e le boemo bo sebetsang ba papiso lipakeng tsa lihlopha tse lipakeng tsa lithuto tsa pele (). Batho ba bang ba bonts'itseng ba bonts'itse ts'ebetso e matlafalitsoeng ea neural ho litloaelo tsa lijo tse ratoang haholo, tse amanang le boemo ba ho se nke lehlakore, phomolong, setlang, thalamus, hypothalamus, parahippocampus, gyrus e ka tlase e tlase (IFG), le "gyrus" e bohareng ea moea. ha ea bontša ts'ebetso e eketsehang libakeng tsena (P <0.01, FWE e lokisitsoe) (Feie. 1A). Nakong ea ho pepesetsoa khatello ea maikutlo le khatello ea ho phomola ho sa jeleng paate, batho ba batenya haholo empa eseng ba hlokang kelello ba bontšitse ts'ebetso e eketsehileng ts'ebetsong ea putamen, insula, IFG le MTG (P <0.01, FWE-e lokisitsoe) (Feie. 1B 'me Letlapa le tlatsetsang 2). Papiso ea batho ba batona ba bapileng le ba ratoang nakong ea boemo ba lijo tseo ba li ratang haholo e bonts'a ts'ebetso ea striatum (putamen), insula, amygdala, cortex ea kapele le sebaka sa Broca, leortortor cortex. Maemong a khatello ea maikutlo, batho ba batona le ba batenya haholo ba bontšitse ts'ebetso e kholo ts'ebetsong ea ts'usumetso, gyrus e ka pele, le infirital e tlase (Tlhahiso e eketsehileng Fig. 2).

Setšoantšo sa 1 

Ka har'a sehlopha neural karabelo ea karohano maemong a cue. Boreleli ba kelello bo bobe ho lihlopha tsa botenya le tse bobebe tse fapaneng tsa ts'ebetso ea kutlo tse bonoang ha li bapisoa le papiso e bapisoang le lijo tse ratoang haholo le maemo a ho se phomole (A) le khatello ea maikutlo khahlanong le ...

Limmapa tsa boko: Ho hanyetsa insulin ho tsamaisana le likarabo tse bonoang tsa neural ho batho ba batenya

Ho hlahloba hore na ho hanyetsa insulin ho ama ts'ebetso ea ts'ebetso ea boko e hlokometsoeng ka mekhoa e ratoang ea lijo le likotsi tsa ketsahalo e sithabetsang, re sebelisitse tlhahlobo-leseling e amanang le voxel ho hlahloba mokhatlo oa HOMA-IR, insulin ea ho itima lijo le maemo a FPG ka phapang e le 'ngoe ho likarabo tsa neural ho maemo ana a cue. Liphakanyo tse matlahali ka ho fetisisa lefapheng leo u le ratang ka ho fetisisa la lijo le maemo a sithabetsang li ile tsa bonoa le HOMA-IR. Ho batho ba batenya empa ba sa thekesele, boleng ba HOMA-IR bo hokahane hantle le ts'ebetso ea neural libakeng tsa corticolimbic-striatal maemong ohle a cue. Haholo-holo, likhokahano tse nepahetseng li fumanoe ka ts'ebetso ea neural ho setamen, insula, thalamus le hippocampus nakong ea boemo ba cue eo a e ratang haholo (Feie. 2A 'me Tlhahiso e eketsehileng Fig. 3A); ka har'a putamen, caudate, insula, amygdala, hippocampus le parahippocampus nakong ea khatello ea maikutlo (Feie. 2B 'me Tlhahiso e eketsehileng Fig. 3A); 'me ka har'a setamen, caudate, insula, thalamus, le anterior le posterior li lula li le maemong a phomolo (Tlhahiso e eketsehileng Fig. 3A 'me Letlapa le tlatsetsang 3).

Setšoantšo sa 2 

Boko ka botlalo, tlhahlobo ea khakanyo e thehiloeng ho voxel e nang le HOMA-IR. Metsoako ea boko ea bo-Axial le li-spplots tse tsamaellanang li bonts'a khokahanyo lipakeng tsa neural activation (li-ights boima) sehlopheng sa botona nakong ea boemo ba cue ea thatohatsi le HOMA-IR (A) le ...

Ha ho makatse hore ebe maemo a insulin a ho itima lijo ka bongata bo feteletseng, empa eseng a leeme, batho ka bomong ba ile ba ikamahanya hantle le libaka tse tšoanang le tsa HOMA-IR. Ho kenyelletsa moo, khokahano e nepahetseng e nang le maemo a insulin e fumanoe maemong a khatello ea maikutlo ka ts'ebetso ea ventral striatal le activation ea amygdalar, mme ho lumellana ho nepahetseng ho ile ha bonoa boemong ba ho se phomole ho kenyang ts'ebetso ea ts'ebetso ea ventral striatal activation (Tlhahiso e eketsehileng Fig. 3B). Ntle le moo, maemo a FPG bathong ba batenya a kopane hantle le ts'ebetso nakong ea boemo ba chate ea thatohatsi ka har'a setamen le thalamus le nakong ea boiketlo ba ho se phomole ho setamen, caudate, insula, thalamus, le anterior le posterior cingulate (Tlhahiso e eketsehileng Fig. 3C 'me Letlapa le tlatsetsang 3).

Takatso ea lijo e eketseha kamora lijo tse u li ratang haholo le likhatello tsa khatello ea maikutlo

Ho lekola likarabo tse lumellanang le tsona, litekanyetso tsa litakatso tsa lijo li ile tsa fumanoa ho tsoa lithuto pele le ka mor'a teko e 'ngoe le e' ngoe ea litšoantšo ka sekala ho tloha 0 ho isa 10. Ho ne ho se na phapang lipapatsong tsa mantlha tsa lijo tse lakatsang litekanyetso pele ho teko e 'ngoe le e' ngoe ea litšoantšo lipakeng tsa lihlopha tse batenya le tse letle [F(1.46) = 0.09, P = 0.76]. Ha litakatso tsa lijo li bapisoa ka mor'a maemo a setšoantšo, ho ne ho e-na le phello ea bohlokoa [F(1.92) = 34.68, P = 0.0001] (Cue ea ratang ka ho fetisisa ea lijo, e leng 6.1 ± 2.9, lean 5.8 ± 2.7; khatello ea khatello ea maikutlo, obese 4.4 ± 3.2, lean 3.1 N 2.2; phello ea sehlopha [F(1.46) = 0.99, P = 0.32] kapa sepheo sa ho sebelisana-ka-maemo-sehlophaF(1.92) = 1.34, P = 0.27)]. Ho bile le keketseho ea litekanyetso tsa litakatso tsa lijo kamora boemo bo ratehang ba lijo le maemo a ho phomola a sa nkeng lehlakore [t(92) = 7.33, P <0.0001] 'me kamora' lijo tseo u li ratang haholo ha o bapisoa le maemo a khatello ea maikutlo [t(92) = 7.09, P <0.0001] mme ha ho na phapang e kholo kamora khatello ea maikutlo le maemo a phomolo a sa jeleng paate [t(92) = 0.25, P = 0.81].

Limmapa tsa boko bo amanang: Liphetoho tse fumanehang kahare ho takatso ea lijo le maemo a khatello ea kelello li lumellana hantle le ts'ebetso libakeng tsa corticolimbic-striatal bathong ba batenya.

Ho etsa lipatlisiso tsa kamano lipakeng tsa likarabo tsa neural le takatso ea lijo, re ile ra lekola kamano ea litekanyetso tsa motho ka mong tse ipolelang tsa lijo tse nang le karabelo ea neural ho sejo sa lijo se ratoang le maemo a khatello. Ho batho ba batenya empa ba sa thekesele, lijo tse labalabelang karabelo ea lijo tse ratoang haholo le maemo a khatello ea maikutlo li tsamaisana hantle le ts'ebetso libakeng tse ngata tsa corticolimbic-striatal (Feie. 3, Tlhahiso e eketsehileng Fig. 4, 'me Letlapa le tlatsetsang 4).

Setšoantšo sa 3 

Boko ka botlalo, khokahano ea khokahano ea voxel e sekaseka takatso ea lijo. Boreleli ba kelello bo bobe bo bonts'a khokahano lipakeng tsa litakatso tse lakatsang lijo le ts'ebetso ea methapo ea kutlo maemong a khatello kelellong (A) le lele (B) lihlopha (tse thibetsoeng ka P <0.05, ...

Libaka tsa boko li tsamaellana le litakatso tsa lijo le insulin: litlamorao

Kamora nako, re ile ra lekola hore na ho hanyetsa insulin ho kopantsoe le takatso ea lijo maemong 'ohle le hore na likamano tsena li ne li kopantsoe ke likarabo tsa neural. Maemo a HOMA-IR a hokahane le litekanyetso tse lakatsang lijo nakong ea ho pepesetsoa lijo tse ratoang haholo lithutong tse motenya (r2 = 0.20; P = 0.04) empa eseng batho ba hlokang leeme (r2 = 0.006; P = 0.75) (Feie. 4A). Maemo a HOMA-IR ha a amane le takatso ea lijo ea khatello ea maikutlo (motenya: r2 = 0.12, P = 0.12; thekesela: r2 = 0.003, P = 0.82) kapa ho phomola ho se nke lehlakore (ho feta: r2 = 0.04, P = 0.38; thekesela: r2 = 0.004, P = 0.80) maemo.

Setšoantšo sa 4Setšoantšo sa 4 

Mohlala oa boits'ebetso: Libaka tsa boko tse fetang tsohle li nka karolo lipakeng tsa HOMA-IR le takatso ea lijo ho batho ba batenya. A: Kamano pakeng tsa maemo a HOMA-IR le litekanyetso tsa litakatso tsa lijo lihlopheng tse hlekefetsang le tse bobebe. B: Ho potoloha libaka tsa neural ...

Ho hlahloba hore na ho itšireletsa ha insulin ho fokotsa lijo tse lakatsehang ka likarabo tsa neural, pele re ile ra lekola ho hasana ho ikhethang libakeng tse neng li tloaelehile mekhatlong ea tsona ea neural ho hanyetsa insulin le ho lakatsa lijo. Lithutong tse batsoang haholo, ketsahalo ea thalamus le VTA / SN e hokahaneng le ho hanyetsoa ka insulin le takatso ea lijo maemong a ratehang a lijo tsa cue (Feie. 4B 'me Letlapa le tlatsetsang 5). Mekhoa e ts'oanang e ile ea bonoa bakeng sa putamen le insula maemong a khatello ea maikutlo le thalamus, caudate, putamen, le insula maemong a ho se nke lehlakore (Feie. 4B 'me Letlapa le tlatsetsang 5). Ha rea ​​fumana libaka tse joalo li pharalatsa lithutong tse tlase.

Ka mor'a moo, re ile ra hlahloba hore na likamano lipakeng tsa HOMA-IR le takatso ea lijo li kopantsoe ke ts'ebetso ea kelello ea tikoloho e tsamaellanang le HOMA-IR le takatso ea lijo (Feie. 4C). Ts'ebetso ea bohanyetsi ba Statistical e ka sebelisoa ho lekola kamano lipakeng tsa tse peli tse fapaneng le ho lekola hore na karolo ea boraro, e ka kenang, e fapaneng, e ka ikarabellang kamanong e bonoang (). E re ka tsela e 'ngoe, re ile ra hlahloba hore na tšebetso ea neural e sebetsang libakeng tsa boko ba corticolimbic-striatal e ne e le lipalo-lipakeng tsa kamano lipakeng tsa HOMA-IR le takatso ea lijo ho barupeluoa ba batenya. Joalokaha ho bontšoa ke phello e ikhethang e sa tobang (a × b tsela) boleng (Letlapa le tlatsetsang 6), likamano lipakeng tsa HOMA-IR le takatso ea lijo li ne li hokahantsoe ke likarabo tsa neural ho thalamus, brainstem (ho kenyeletsoa VTA / SN), le cerebellum e maemong a ratehang a cue le setamen le insula maemong a khatello ea cue.

CONCLUSIONS

Re hlokometse ts'ebetso e makatsang ea ts'ebetso ea corticolimbic-striatal ka bongata bo feteletseng, empa eseng re leqe, batho ka bomong ba arabelang moqoqong oa lijo tse re ratang le khatello ea maikutlo ha ba bapisoa le maemo a ho se phomole. Likarabo tsa Neural libakeng tsena nakong ea ho pepeseha hoa chate ea lijo li lumellana le lithuto tse fetileng (,,,). Likarabo tse hlakileng tse tsoang ho li-neural tse bonoang lithutong tsa botenya mecheng ea bokong li bile le tšusumetso e matlafatsong ea moputso, mohopolong oa maikutlo, ho latsoa tatso le ho hlaka litlatse, li hokahane le HOMA-IR, tekanyo ea ho hanyetsa insulin, le hyperinsulinemia. Ntle le moo, likarabo tsena tsa neural li arabile kamano lipakeng tsa insulin le ho lakatsa lijo ho batho ba batenya, ho fana ka maikutlo a hore bathong ba batenya, ho hanyetsa insulin ho ka ama ka kotloloho kapa ka tsela e sa tobang mekhoa ea neural e tsamaisang litakatso tsa ho ja lijo tseo u li ratang, 'me hangata e le lijo tse matla haholo.

Seo re se fumaneng se lumellana le, 'me re atoloha, mosebetsing o fetileng o bonts'a hore insulin e sebetsa e le sesupo sa taolo ea methapo ea methapo ea lijo le boima ba' mele (,). E lumellana le datha e behang methapo ea moputso oa hypothalamus le dopaminergic maemong a botenya le liketsong tsa insulin (-), 1) batho ba batenya haholo ba bonts'itse ts'ebetso e eketsang ts'ebetsong libakeng tsa corticolimbic-striatal ho kenyeletsoa le striatum (bobeli ba setamen le caudate), insula, thalamus le 2) bokaholimo ba khanyetso ea insulin, joalo ka ha bo hlahlojoa ke HOMA-IR, bo lumellana hantle le ts'ebetso ea striatum le insula ha ho arabeloa lijo tse ratehang tsa lijo le maemo a khatello ho batho ba batenya. Lintlha tsena li tšehetsoa ke mosebetsi oa pejana o bonts'ang liphetoho tse mabapi le insulin sensitivity ho VTA ho fetola likarabo tse tlase tsa merero ho striatum (); insulin e matlafatsoang ke "glucose metabolism" ho "ventral striatum" e fokotsehile lithutong tse hananang le insulin (); mme ts'ebetso ea ts'ebetso ea insular le hippocampal ho arabela litlhaselong tsa lijo e amana ka kotloloho le hyperinsulinemia (). Ha ho nahanoa hammoho, lipatlisiso tsena li ka ba le litlamorao tsa bohlokoa litabeng tsa boits'oaro bo amanang le lijo mme li fana ka maikutlo a hore ho hanyetsa insulin ho ka sitisa bokhoni ba insulin ba ho hatella litsela tsa ts'ebetso, ka ho etsa joalo ho eketsa khatello ea maikutlo le lijo tse amanang le neue ka mokhoa o ikhethileng ho batho ba batenya.

Litekanyetso tse ikhethileng, tse itlalehang tsa lijo tse batlang litakatso, tse itšetlehileng ka maikutlo a motho ka mong, ha lia ka tsa fumanoa li fapane haholo ka lipalo ho batho ba batenya le ba batenya. Ho ekelletsa moo, lithuto tse batenya le tse tepelletseng li thathamisitse lijo tse tšoanang tseo ba li ratang ka ho khetheha bakeng sa lithahasello tsa bona tseo ba li ratang haholo (Letlapa le tlatsetsang 7), ka bongata ba lijo li na le mafura a mangata le lik'halori. Kahoo, liphapang tse hlokometsoeng ha li kenyelle karohano lijong tseo re li batlang empa, ho fapana le moo, hore na leseli lena le sebetsoa joang le ho hlalosoa joang, mohlomong le mekhoa e metle ka mor'a ho pepesetsoa bophelo ba 'nete litloaelong tse ratoang. Hoa hlokomeleha, leha ho le joalo, hore boemo ba HOMA-IR bo feta ka bongata, empa ha bo thekesele, batho ka bomong ba ikopantseng le litekanyetso tse amanang le lijo tse amanang le lijo tse amanang le takatso. Ho lumellana le tlhokomeliso ena, ha re hlahloba hore na ke ts'ebetso efe ea boko e amanang le likarolo tsa HOMA-IR le litekanyetso tsa takatso ea lijo, re fumane libaka tse ngata tsa boko ho batho ba motenya empa eseng batho ba hlokang kelello. Likarolo tsena ha li kenyeletse feela VTA le SN empa hape le striatum, insula, le thalamus, tseo ka ho latellana li kenya letsoho ts'ebetsong ea ts'usumetso ea meputso le ho arabela khatello ea maikutlo (), tatso le ho bonts'a lipuisano (,), le leseli la tlhaiso-leseling ea maikutlo a paripheral ho cortex (). Lintlha tsena li fana ka maikutlo a hore ho hanyetsa insulin, le / kapa litlamorao tsa ho hanyetsoa ke insulin, li ka holisa kapa tsa khotsofatsa likarabo maemong a potolohang a neural a amang takatso ea lijo bakeng sa lijo tse lakatsehang haholo mme qetellong a baka phaello e eketsehileng ea boima. Kamano ea bohlokoa lipakeng tsa insulin le HOMA-IR maemo a ho lakatsa lijo le ts'ebetso ea ts'ebetso ea boko tse bonoang ho monokotšoai, empa e se leeme, batho ka bomong ba ka amana le ho haelloa ke ho fapana hoa maemo a insulin ho batho ba nang le / .

Mekhatlo ea tšehetso ea data lipakeng tsa khatello e phahameng e sa laoleheng, khatello ea maikutlo, BMI e phahameng, le phaello ea boima ba mmele (,). Khatello ea maikutlo e susumetsa mekhoa ea ho ja (,), ho ata ha tšebeliso ea lijo tse potlakileng (), lijo tse monateloang (), le lijo tse nang le khalori e matla le tse fumanehang habonolo (), 'me khatello ea maikutlo e amahantsoe le ho eketseha hoa boima ba' mele (). Thutong ea rona, nakong ea ho pepesa khatello ea litabatabelo tsa takatso ea lijo tse batenya haholo, empa eseng ka leeme, batho ka bomong ba ile ba lumellana hantle le ts'ebetso ho caudate, hippocampus, insula, le putamen. Likamano tsena tse fapaneng li fana ka maikutlo a hore litakatso tsa lijo tse amanang le khatello ea maikutlo li tsamaisoa ke litakatso tse ikhethileng tsa batho ba batenya ebile li phahamisa monyetla oa hore phapang ena e ka eketsa kotsi ea ho ja lijo tse lakatsehang, tse monate haholo nakong ea khatello ho batho ba batenya. Liphumano tsena li lumellana le data e fanang ka maikutlo a hore ho ja ho tsamaeang le khatello ea maikutlo ho atile ho basali ba batenya haholo (), athe ho ja ho tlisoang ke khatello ea maikutlo ho na le phello e sa lumellaneng tšebeliso ea lijo ho batho ba mahlahahlaha (). Kamora ho pepesetsoa khatello ea kelello, batho ba nonneng haholo ba na le takatso e matla ea lijo le lino tse bobebe le ho ja lijo tse phahameng haholo ha li bapisoa le batho ba neng ba le maemong a tšoanang (). Ha ho bapisoa le batho ba nang le li-BMI tse tlase, ba nang le li-BMI tse phahameng ba bonts'a likamano tse matla pakeng tsa khatello ea kelello le ho eketsa boima ba bokamoso (). Ha li kopantsoe hammoho, liphuputso tsena le seo re se fumaneng li fana ka maikutlo a hore batho ba batenya haholo ba ka ba kotsing ea ho sithabetsoa ke tšebeliso ea lijo tse amanang le khatello ea maikutlo le ho nona ka morao ho moo. Kaha bobeli ba lijo tse ratoang haholo- le khatello ea maikutlo tse bakiloeng ke corticolimbic-striatal neural activation, ho ka ba molemo lithutong tsa kamoso ho etsa maemo a bophelo ba khatello e matla ho hlahloba ts'ebetso ea potoloho ea neural ha batho ba batenya ba pepesetsoa nako e le 'ngoe. likhatello tse matla tsa bophelo le litabatabelo tsa lijo tseo u li ratang haholo.

Qetellong, hoa hlokomeleha hore batho ba batenya haholo ba nang le bopaki ba ho hanyetsa insulin ba bonts'itse liphetoho tse teng litakatsong tsa lijo le ha li le maemong a phomolo. Corticolimbic-striatal activation e bonoang ho batho ba batenya nakong ea boemo ba ho se nke lehlakore e kopantsoeng le takatso e matla ea lijo. Maemo a HOMA-IR ho batho ba batenya le bona a kopantsoe le likarabo tsa neural nakong ea boemo ba ho phomola, a fana ka maikutlo a hore boemo bo sa tsitsitseng ba insulin bo amana le ts'ebetso e phehellang libakeng tsa boko ba corticolimbic-striatal esita le nakong ea maemo a sa jeng lijo le maemo a seng matsapa (mohlala. , nakong ea libaka tsa phomolo kapa tsa phomolo) ho batho ba batenya haholo, 'me kamano ena e ka boloka takatso ea lijo le ho khothaletsa boits'oaro ba ho ja nakong ea libaka tse sa rateheng kapa tsa motheo.

Sebopeho sa karolo ena ea thuto ena se kenyelletsa tlhahlobo ea maikutlo a ho etsa lintho ka mokhoa o hlakileng. Boithuto ba nako e telele bo tla thusa tlhahlobo ea hore na botenya bo fella ka karabelo e eketsehang litekanyetsong tsa lijo le khatello ea maikutlo likarolong tsa ts'usumetso ea moputso kapa hore na liphapang tsa neural le mekhatlo ea tsona e hanyetsang insulin li kile tsa ba teng pele. Tekanyo ea ho hanyetsa insulin e sebelisang HOMA-IR ha e na mokhoa o nepahetseng o fuoang mokhoa oa ts'ebetso ea ts'ebetso ea euglycemic, leha e amana haholo le karabelo ea insulin ea ts'ebeliso 'me e sebelisoa haholo lipatlisisong le litloaelong tsa bongaka.). Litekanyetso tsa insulin le tsoekere li ile tsa huleloa hoseng ho etsa hore ho hlahlojoe kutloisiso ea insulin ho sebelisa mehlala ea mali e potlakileng bakeng sa lipalo tsa HOMA-IR; Mekhoa ea ho nahana ka fMRI e ile ea etsoa thapama e le hore lithuto li se ke tsa tlala haholo kapa tsa tlala. Lithutong tsa nako e tlang, ho nka litekanyetso tsa mali kapele le pele, ka nako le ka mora MRI ho ka fana ka leseli le bohlokoa, leha ho ka ba le mathata a teng (mohlala, tšusumetso ea phlebotomy lits'ebetsong tsa karabelo ea khatello ea maikutlo). Lisampole tse potlakileng tsa mali ha lia ka tsa fumanoa ka letsatsi la seboka sa fMRI; ka hona, kamano ea nakoana lipakeng tsa methapo ea metabolic le likarabo tsa neural li ke ke tsa etsoa mme ho ka ba le liphapang tse pakeng tsa sehlopha botsitsong ba mehato ea HOMA-IR ho batho ba batenya le ba se nang leeme e ka bang le tšusumetso ho lumellano e hlokometsoeng thutong ea hajoale. Habohlokoa, leha ho le joalo, mehato ea HOMA-IR e bonts'oa e na le phapang e fokolang ea intra- le e kopanetsoeng ho li-feta tsa nondiabetesic (le boima ba mmele o mongata () batho ka bomong, le insulin ea 'mele ea "plasma" le "glucose" e tsitsitseng e fumanoe e tsitsitse lithutong tse phetseng hantle ka nako ea selemo sa 4 (). Ho kenyelletsa moo, li-coefficients tsa phapang ea HOMA li pakeng tsa 7.8 le 11.7% (). Leha ho na le litekanyetso tsena tsa ho ithuta, datha ea rona e fana ka bopaki ba pele ba hore ho hanyetsa insulin ka kotloloho kapa ka kotloloho e bapala karolo ea bohlokoa ts'ebetsong ea methapo e amanang le mekhoa ea lijo eo u e ratang haholo le khatello ea maikutlo le hore likarabelo tse joalo tsa neural li lekola lijo tse lakatsoang ke batho ba batenya. Hore na ho hanyetsa insulin ke ketsahalo ea mantlha kapa phetoho ea karabelo ea boko e etsahala ka nako e telele ho pepeseha hoa hyperinsulinemia ea morao-rao le ka lebaka la khatello ea methapo ea insulin receptors ho lula ho sa tsejoe; leha ho le joalo, liphetho tsena li na le litlamorao tsa bohlokoa tsa kalafo.

Ka keketseho e kholo ea boteng ba botenya lilemong tse mashome a mararo tse fetileng, liphumano tsena li na le litlamorao tse ngata tsa kliniki bakeng sa kalafo ea ho se sebetse hantle ha metabolic le thibelo ea lefu la tsoekere la mofuta oa 2. Liphumano tsa morao-rao li bonts'a hore ho hanyetsa insulin ho botona ho amana le mekhoa ea neural e laolang lijo kapa litloaelo tse amanang le lijo tse kang ho lakatsa lijo kapa takatso ea ho fumana le ho ja lijo. Liphumano tsena li fana ka maikutlo a hore batho ba nang le "metabolic phenotype" ena e fetotsoeng ba ka ba kotsing ea ho eketsa boima ba 'mele bo ntseng bo tsoela pele kapa bo phehellang. Ho feta moo, ha libaka tse ngata tsa neural tse amehang li le bohlasoa, re hakanya hore taolo e fokotsang taolo e mabapi le boits'oaro bo amanang le lijo e ka hlaha bathong ba joalo ba batenya, e leng ho felletseng ka ho nts'etsapele botona le botšehali ba insulin.

Re phethela ka hore ho pepesehela litšoantšo tse ratoang haholo ke batho ba ratang lijo le maemo a liketsahalo a sithabetsang ho khothaletsa ts'ebetso ea libaka tse khothatsang boko le ho lakatsa lijo ho batho ba batenya ba insulin. Hoa khahla ho hakanya hore insulin e ka hanyetsa bothateng bo boholo 'me ea kenya letsoho ho khothalletseng lijo hore li je lijo tse ka etsang hore batho ba kotsing ea ho ja haholo, ba hlahise matla a ho khanna boima ba mmele. Ka hona, ho etsa lipatlisiso tsa litlamorao tse bohareng le boits'oaro bo botle ba meriana e fetolang ho hlaseloa ha insulin ho ka fana ka leseli ho mekhoa e meng ea kalafo ea ho hlahisa takatso ea lijo tse matla haholo tse fumanehang habonolo.

 

Boitsebiso bo Eketsehileng

Lintlha tse tlatsetsang: 

lumela hore baa fokola

Mosebetsi ona o tšehelitsoe ke Setsi sa Naha sa Lefu la Ts'oaetso le Ts'oaetso ea Mafura le Liphio tsa Naha / National Institutes of Health T32 DK07058, Diabetes Mellitus and Disallen of Metabolism; T32 DK063703-07, Koetliso ea Pediatric Endocrinology le Lefu la Tsoekere; Setsi sa Patlisiso ea lefu la tsoekere le Endocrinology P30DK045735; le R37-DK20495 le NIH Roadmap ea lithuso tsa Lichelete tsa Patlisiso ea Bongaka RL1AA017539, UL1-DE019586, UL1-RR024139, le PL1-DA024859.

Ha ho likhohlano tse ka 'nang tsa e-ba le thahasello tse amanang le sehlooho sena.

AMJ e ile ea etsa tlhahlobo ea tlhaiso-leseling, ea kenya letsoho phetolelong ea data, mme ea ngola sengoloa. RS e ne e ikarabella ho moralo oa ho ithuta, lichelete, le pokello ea data; kenya letsoho phetolelong ea data; mme a ngola sengoloang. CL e ile ea etsa tlhahlobo ea data. DMS e kentse letsoho phetolelong ea data. RSS e kentse letsoho phetolelong ea data mme ea ngola buka e ngotsoeng ka letsoho. MNP e ne e ikarabella ho moralo oa ho ithuta, lichelete, le pokello ea data; kenya letsoho phetolelong ea data; mme a ngola sengoloang. MNP ke motheisi oa mosebetsi ona, ka lebaka leo, o ne a na le phihlello e felletseng ea tlhaiso-leseling eohle mme o nka boikarabello ba ho nepahala ha tlhaiso-leseling le ho nepahala ha tlhahlobo ea data.

Likarolo tsa thuto ena li hlahisitsoe ka sebopeho se sa fumaneheng ho 71st Science Science Sission of American Diabetes Association, San Diego, California, 24-28 June 2011.

Mongolo o botlaaseng ba leqephe

 

Sehlooho sena se na le Inthaneteng ea Data Inthaneteng ho http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc12-1112/-/DC1.

 

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