Ukuphonononga indima yeBHB kwiMpilo yengqondo: Ukumodareyithwa kwe-Epigenetic njengoNyango lwe-Metabolic Psychiatry
Ixesha lokufunda eliqikelelweyo: 16 imizuzu
Ngoko xa sithetha ngokutya kwe-ketogenic okwenza i-ketones, kwaye ezo ketone ziyimizimba ye-molecular signaling, yile nto ndiyithethayo. I-BHB ngowona mzimba we-ketone ofundwe kakuhle kwiincwadi ngeli xesha. Oko akuthethi ukuba ezinye imizimba ye-ketone ayinayo imiphumo ye-molecular signaling okanye iimpembelelo. Kuthetha nje ukuba uphando, ngexesha leli nqaku, lugxininise kule miphumo ibonwe kwi-BHB.
I-BHB yayisetyenziselwa ukubonwa nje ngokuba yi-metabolic byproduct kodwa sele ifumana ukukhawuleza iminyaka emininzi ekuqapheliseni indima yayo kwinkqubo eyinkimbinkimbi ye-epigenetic modulation, indima enefuthe elinzulu kwi-neuropsychiatric disorders.
I-Epigenetics: I-Architect efihlakeleyo yeGene Expression
Ngaphambi kokuba ndingene kwiinkcukacha ezithile zeBHB, ndicinga ukuba kunceda ngokwenene ukuqonda ingcamango ye-epigenetics. Ukucacisa oku, ndingathanda ukusebenzisa umzekeliso oqhelekileyo wethala leencwadi kunye nononcwadi. Yiba nomfanekiso weDNA yakho njengethala leencwadi elikhulu elinengqokelela enkulu yeencwadi ezizele lulwazi lwakho lwemfuza. I-Epigenetics iyafana nomphathi wethala leencwadi othatha isigqibo sokuba zeziphi na iincwadi ezithatyathwe kwiishelufa ukuba zifundwe kwaye ezishiyeke zibekwe ecaleni. Unoncwadi unamandla kakhulu kule meko, awuvumi? Umgcini-zincwadi akazitshintshi iincwadi ngokwazo - ukulandelelana kwe-DNA kuhlala kungatshintshi - kodwa unolayibrari uphembelela ukuba zeziphi iindawo zekhowudi yezofuzo ezivezwayo okanye "zifundwe," kwaye ezingekho. Kweli thala leencwadi, iincwadi (DNA) zixabiseke kangangokuba azinakususwa. Nangona kunjalo, xa incwadi ikhethiwe ukuba ifundwe, inkqubo eyahlukileyo (i-transcription) yenza iikopi zeefotokopi (i-messenger RNA; mRNA) yamaphepha ayimfuneko. Ezi kopi zekopi ziphuma kwithala leencwadi, zithwele inkcazelo efunekayo ukuze iseli ivelise iiproteni.
Ulandelelwano lwe-DNA kwiijini luhlala lufana kungakhathaliseki ukuba iimpembelelo ze-epigenetic. Ndicinga ukuba iikhonsepthi zofuzo kunye ne-epigenetics zinokubhida kubantu abangazaziyo ezi ngcamango. Ukuba ubhideka zezi, akuwedwa. Makhe sijonge eminye imizekelo esinceda siqonde.
Ukutya ukutya okutyebileyo kwi-Vitamin B12, njengenyama, ubisi, kunye namaqanda, kunokuchaphazela iimpawu ze-epigenetic. Ngelixa iVithamin B12 ingalutshintshi ulandelelwano lwe-DNA yemfuza enxulumene nemithambo-luvo kunye nempilo yeeseli zegazi, idlala indima ephambili ekugcineni iipatheni ze-DNA ezinempilo, ezibaluleke kakhulu ekubonakalisweni okufanelekileyo kwezi mfuzo.
Ukubonakaliswa kwezinto ezingcolileyo kunye neekhemikhali, ezifana neentsimbi ezinzima, kunokubangela utshintsho lwe-epigenetic. Ezi tyhefu azilutshintshi ulandelelwano lwe-DNA lwe-gene, kodwa lunokuguqula i-pattern ye-DNA. Oku kuchaphazela indlela iijini ezithile ezivakaliswa ngayo, ezinokuchaphazela impilo ngaphandle kokutshintsha ikhowudi yezofuzo ngokwayo.
Uxinzelelo lwengqondo kunye namava abuhlungu angabangela ukuguqulwa kwe-epigenetic. La mava awatshintshi ukulandelelana kwe-DNA ngaphakathi kwezakhi zofuzo ezinxulumene nempendulo yoxinzelelo kunye nempilo yengqondo. Nangona kunjalo, banokutshintsha indlela ezi jeni zibonakaliswa ngayo ngeendlela ezahlukeneyo. Oku kuguqulwa kwembonakalo yemfuza kunokuchaphazela impendulo yoxinzelelo lomzimba kwaye ichaphazele i-metabolism yeselula kunye nomsebenzi we-mitochondrial kuba iimpendulo zoxinzelelo zinxulunyaniswa ngokusondeleyo nokusetyenziswa kwamandla kunye nempilo yeselula. Ngaloo ndlela, ngelixa ikhowudi yezofuzo ihlala ingatshintshi, indlela umzimba ophendula ngayo uxinzelelo kwinqanaba le-molecular inokuguqulwa kakhulu.
Ukuzivocavoca kuchaphazela ukubonakaliswa kofuzo lwe-PPARGC1A, olubalulekileyo kwi-metabolism yamandla. Ngelixa umthambo ungatshintshi i-DNA yokwenyani ye-PPARGC1A gene, inyusa umsebenzi wayo. Oku kukhokelela ekwandeni kwemveliso ye-mitochondrial kwiiseli ze-muscle kunye nokusebenza kakuhle kwamandla, konke ngokuguqulwa kwe-epigenetic ngaphandle kokuguqula ukulandelelana kwe-DNA yemfuza.
Ukulawulwa kwe-gene expression (aka epigenetics) ifezekiswa ngeendlela ezahlukeneyo. Kweli nqaku, siza kufunda malunga nokuguqulwa kwe-histone, i-DNA methylations, kunye ne-microRNAs (i-miRNAs), ezaziwa ngokuba zii-RNA ezingezizo iikhowudi. Ekugqibeleni, uya kuqonda ngcono kancinci ukuba iziphumo ze-BHB zinefuthe njani kwezi nkqubo zibalulekileyo kwi-gene expression ngendlela echaphazela impilo yengqondo.
Ukuqonda i-β-Hydroxybutyrate: Ngakumbi kuneFuel nje
Kwabo batsha kwiblogi kunye nokutya kwe-ketogenic, masikunyuse ngokukhawuleza! I-β-Hydroxybutyrate ngumzimba we-ketone oveliswa kakhulu kwisibindi ngexesha lokunciphisa i-carbohydrate intake, njengokuzila ukutya okanye ukuthobela ukutya kwe-ketogenic. Kula mazwe, umzimba usuka ekusebenziseni i-glucose njengomthombo wayo oyintloko wokutshisa amafutha, okukhokelela ekuveliseni i-BHB kunye nezinye ii-ketones. Unokwenza i-BHB ngokulandela ukutya kwe-ketogenic, okanye ungathatha i-BHB njengesongezelelo okanye ukudibanisa ezimbini.
Kodwa kufuneka ukwazi ukuba indima yeBHB idlulela ngaphaya kokuba ngumthombo wamandla ongomnye. Isebenza njengomqondiso we-molecule echaphazela uluhlu lweenkqubo zebhayoloji. Phakathi kweendima zayo ezinomdla kukukwazi ukulungelelanisa kunye nokuphembelela ukubonakaliswa kofuzo ngeendlela ezahlukeneyo ze-epigenetic ezihambelana nesimo sengqondo kunye nokusebenza kwengqondo.
Indima ye-β-Hydroxybutyrate (BHB) kwiMpilo yengqondo: Impembelelo ye-Epigenetic kunye nokusebenzisana kwe-GPCR
Ngoko ke, ukuqonda indima eninzi ye-β-Hydroxybutyrate (BHB) kwimpilo yengqondo siya kufuneka sihlolisise impembelelo ye-epigenetic, kwaye ngokukodwa ukusebenzisana kwayo kunye ne-G protein-coupled receptors (GPCRs). I-GPCRs yintsapho enkulu yee-cell cell receptors ezidlala indima ephambili ekudluliseni imiqondiso ukusuka ngaphandle kweseli ukuya ngaphakathi. Zibophe ngee-ligands ezithile (njengamahomoni, i-NTs, kunye ne-metabolic byproducts efana ne-BHB) kwaye oku kusebenze iiprotheni ze-G.
Iiprotheyini ze-G, ezimfutshane kwi-guanine nucleotide-binding proteins, zilusapho lweeproteni ezisebenza njengotshintsho lwemolekyuli ngaphakathi kweeseli. Zibekwe kwicala langaphakathi le-membrane yeseli kwaye zisebenze yi-GPCRs.
Nje ukuba iiprotheyini ze-G zisebenze ngaphakathi kwiseli, zenza amanyathelo amaninzi okubonisa i-cascades ezibandakanya iimolekyuli ezibalulekileyo zomlamli ezifana nabathunywa besibini (umzekelo, i-cAMP, i-calcium ions) kunye ne-kinases (ii-enzymes ezongeza amaqela e-phosphate kwezinye iiprotheni). Ezinye zeendlela zokubonisa eziqaliswe yi-GPCRs ngokungathanga ngqo kunye noomatshini be-epigenetic beseli.
Ngokomzekelo, i-cascade abayiqalayo inokukhokelela ekusebenziseni i-kinases ukuba i-phosphorylate transcription factor okanye ezinye iiprotheni ezibandakanyekayo kulawulo lwemfuza. Ngendlela elula, xa iiprotheyini ze-G zisebenza, ziqala ukusabela kwekhonkco, ekugqibeleni zisebenze i-enzymes ethile (umzekelo, i-kinases). Ezi kinases ke ziguqula iiprotheyini eziphambili (njengezinto ezibhaliweyo) ezilawula ukuba zeziphi iijini ezisebenzayo kwiseli. Yile ndlela umqondiso ovela ngaphandle kweseli (njengehomoni) unokukhokelela ekutshintsheni into eyenziwa yiseli, kubandakanywa notshintsho apho imfuza esebenzayo.
Ngoko, konke oku kunomdla kakhulu, kodwa yintoni esiyaziyo ngendima yeBHB ekusebenzisaneni ne-GPCRs? I-GPR109A kunye ne-GPR41 ziintlobo ezithile ze-G protein-coupled receptors (GPCRs) apho iziphumo ezithile zeBHB ziye zachongwa kwiincwadi zophando.
I-BHB isebenze i-GPR109A kwi-adipocytes, ukunciphisa i-lipolysis kunye nakwiiseli ze-immune kunye ne-endothelial. Oku kusebenze kunokuvelisa iziphumo ezichasayo, ezinokunciphisa umngcipheko we-atherosclerosis. Oku kunokuguqulelwa njani kwiziphumo ezithe ngqo kwimpilo yobuchopho kwaye, ke ngoko, ibonelele ngeziphumo zonyango lwesifo sengqondo kunye nokuphazamiseka kwemithambo-luvo? Ewe, iimpembelelo ezichasayo, ezifana nezo zibonelelwe ngokusebenzisana kwe-BHB kunye ne-GPR109A yokusebenza kwiiseli ze-immune kunye ne-endothelial, zibalulekile kwingqondo! Ukudumba okungapheliyo yinto eyaziwayo kwiingxaki ezahlukeneyo ze-neurological, ke ukunciphisa ukudumba kunokukhusela ingqondo kwi-neuroinflammation. Umsebenzi ophuculweyo we-endothelial uphucula ukuhamba kwegazi kwingqondo kwaye uqinisekisa ukuhanjiswa okungcono kwe-oksijini kunye nezondlo-iindlela ezibalulekileyo zobuchopho obusebenzayo kwaye, ngoko ke, ukuzinzisa isimo sengqondo kunye nokusebenza kwengqondo.
Nangona kunjalo, iziphumo ze-BHB ziyanqanda okanye "zichasayo" kwintetho ye-GPR41. Inokuba luncedo njani iBHB kwindlela yokuthetha? Oko kubonakala kuchasene, akunjalo? Ke, makhe siqale ukuhlola oku kumxholo wesifo seswekile.
Kwisifo sikashukela, intetho engabonakaliyo ye-GPR41 ihambelana nokuncipha kwe-insulin secretion. Oku kuncipha kucingelwa ukuba negalelo kumngeni weeseli ze-beta ze-pancreatic ekuphenduleni ngokufanelekileyo kumanqanaba aphezulu e-glucose, uphawu oluphambili lwe-2 yeswekile. Ukusebenza kwe-GPR41 kwiiseli ze-beta ze-pancreatic ngokwenene kunokudlala indima ekuvimbeleni i-glucose efanelekileyo-evuselelwe ukukhutshwa kwe-insulin phantsi kweemeko zesifo seswekile.
Nangona kunjalo, njengoko sele kuchaziwe, i-BHB ibonwe ukuba ichasene ne-GPR41. Kutheni ibalulekile nje loo nto? Ngenxa yokuba ukuchasana (ukuchasana okanye ukucotha) ukubonakaliswa kwe-GPR41 kunokuba nemiphumo emihle ye-metabolic.
Ngokusebenza ngokuchasene ne-GPR41, i-BHB inokwandisa i-insulin secretion, ngaloo ndlela iphucula ulawulo lwe-glucose yegazi. Lo matshini ubonisa indima ebalulekileyo kwi-BHB ekulawuleni isifo sikashukela, ngokukodwa ekuphuculeni ukunyamezela kwe-glucose kunye novelwano lwe-insulin. Kodwa kuthekani ngokugula ngengqondo kunye nemiba ye-neurological ephawulwe kukungasebenzi kakuhle kwemetabolism kwingqondo? Ndingatsho ukuba ezi ziphumo zibalulekile kwimpilo yengqondo.
Iswekile yegazi ezinzileyo ibalulekile ekusebenzeni kwengqondo, kwaye ukuphuculwa kokulawulwa kweglucose ixhasa impilo yengqondo, yehlisa umngcipheko wezifo ze-neurodeergenerative, inceda ukuzinzisa imo, kwaye inikezela nge-neuroprotection iyonke. Kuye kwaboniswa ukuba ukuchasana kweBHB kwe-GPR41 kuchaphazela ukusetyenziswa kwamandla kunye nomsebenzi we-nerve onovelwano. Intsebenziswano ekwachaphazela i-glucose homeostasis ngokulawula ukukhutshwa kwe-insulin.
I-antagonism ye-GPR41 yi-BHB nayo ichaphazela umsebenzi we-nerve onovelwano. Ukulawula umsebenzi we-nerve enovelwano kubalulekile kuba yinxalenye yempendulo yomzimba kuxinzelelo. Ngokumodareyitha le mpendulo, i-BHB inokusebenzisa impembelelo ekulawuleni imiphumo enxulumene noxinzelelo kwingqondo, esaziyo ukuba inokuphazamisa i-metabolism yengqondo. Indima yolu nxibelelwano kwi-glucose homeostasis kunye nokukhuselwa kwe-insulin ibalulekile kwimpilo yobuchopho, kwaye ukungalingani kunokukhokelela kwimiba yeemvakalelo kunye neyokuqonda kunye nomngcipheko wokwanda kwezifo ze-neurodeergenerative.
I-BHB idlala indima ebalulekileyo kwi-inflammatory, neurologic, kunye izifo ze-metabolic njengeendogenous GPCRs ligand.
Yena, Y., Cheng, X., Zhou, T., Li, D., Peng, J., Xu, Y., & Huang, W. (2023). I-β-Hydroxybutyrate njenge-epigenetic modifier: Iindlela eziphantsi kunye neziphumo. IHeliyon. https://doi.org/10.1016/j.heliyon.2023.e21098
Akunzima ukubona indlela ii-BHB ezichaphazela ngayo ii-GPCR zineempembelelo ezibalulekileyo kwimpilo ye-metabolic, kwaye, ngoko ke iziphumo ezithe ngqo kwimpilo yengqondo.
Kwaye ezo ziziphumo ezingathanga ngqo zeBHB kwi-epigenetic expression ngokusebenzisa i-GPCRs. Masikunyuse ngokukhawuleza ngeendlela ezithe ngqo ezibandakanyekayo ukuze uqonde ngcono ukuba kutheni le nto ilunyango olunamandla kangaka.
I-Methylation 101: Ukumisela iSigaba sendima yeBHB kuLawulo lweGene
I-BHB ineempembelelo ezinamandla kwi-methylation. Ngaphambi kokuba sithethe ngabo, kufuneka sichithe umzuzwana sithetha malunga nokuba yintoni i-methylation kuba yinkqubo esisiseko yezinto eziphilayo edlala indima ebalulekileyo kulawulo lwemfuza kunye ne-epigenetics.
Musa ukwenza nzima kakhulu eli gama. Kubonakala kusongela ekuqaleni, kodwa kwi-core, i-methylation yongezwa nje kwamaqela amancinci emichiza ebizwa ngokuba ngamaqela e-methyl kwiindawo ezithile ze-DNA yethu okanye kwiiprotheni (i-histones) apho i-DNA ihlanganiswe khona. Benza 'njengeethegi' ezinokuthi zisebenze okanye zithulise imfuza. Xa amaqela e-methyl eyongezwa kwimimandla ethile, angakwazi 'ukucima' i-gene, ukukhusela ukuba ingasetyenziselwa ukudala iiprotheni. Xa la maqela amancinci e-methyl engekho, 'avula' imfuza ngokuyivumela ukuba ikhutshelwe ngokusebenzayo kwiiprotheni. Iithegi zeMethyl zicima izakhi zofuzo, kwaye ezo zifuzo azenzi iiprotheni. Iijini ezingenayo i-methyl tag zivula kwaye zenze iiproteni.
Kwithala leencwadi kunye nesifaniso soononcwadi, i-DNA methylation inokufaniswa nononcwadi obeka iimpawu ezithile okanye iithegi kwiincwadi ezithile. Ezi ziphawuli aziwutshintshi umxholo weencwadi (ulandelelwano lweDNA) kodwa zibonisa ukuba incwadi kufuneka ifumaneke lula okanye hayi. Kulo mzekeliso, xa incwadi ibhalwe ngumgcini-zincwadi (methylation), luphawu lokuba le ncwadi akufanele ivulwe okanye ifundwe okwangoku. Oku kufana nendlela i-methylation kwi-DNA inokucinezela ngayo ukubonakaliswa kofuzo oluthile. Kufana nokuba umphathi-thala uthi, “Le ncwadi ayifuneki ngoku; masiyigcine eshelufini kwaye ingayijikelezi. Ngokwahlukileyo, ukungabikho kwethegi enjalo kuthetha ukuba incwadi iyafumaneka ukuba ifundwe, kufana nendlela ukungabikho kwe-methylation kunokuvumela i-gene ukuba ibonakaliswe.
Amanqanaba aphakamileyo e-β-Hydroxybutyrate (BHB) anokuthintela umsebenzi we-enzymes njenge-DNA methyltransferases (DNMTs). Ii-DNMTs zinoxanduva lokongeza amaqela e-methyl kwi-DNA, inkqubo ephambili kulawulo lwemfuza eyaziwa ngokuba yi-methylation. Ngokuthintela ezi enzymes, i-BHB inokunciphisa i-methylation ye-DNA, engakhokelela ekutshintsheni kwintetho yezakhi ezithile zofuzo.
Masenze umzekelo ukuququzelela ukufunda kwakho!
I-BHB inqanda i-enzymes ezikhuthaza i-methylation. Oku kuvinjelwa kwe-BHB kuvumela i-gene ye-PGC-1a (i-PPARG coactivator 1a) ukuba ilawule. Oku ngenene, kuhle ngokwenene. I-PGC-1a ibalulekile kumsebenzi we-mitochondrial kunye ne-biogenesis. Ukulawulwa kwale gene kudlala indima ebalulekileyo ekugcineni umsebenzi wokuphefumla we-mitochondrial kunye namazinga e-acid oxidation.
Ukuba ufuna ukwazi ukuba zeziphi izakhi zofuzo eziphenjelelwa yi-BHBs iziphumo kwi-methylation, ngoko uya kuvuya ngokwenene eli nqaku endilibhalileyo malunga naloo nto!
Kuyaziwa ngokubanzi ukuba imizimba ye-ketone ayisebenzi nje njenge-ancillary fuel endaweni ye-glucose kodwa iphinda ibangele i-anti-oxidative, anti-inflammatory, kunye ne-cardioprotective iimpawu ngokubophelela kwiiprotheni ezininzi ezijoliswe kuzo, kuquka i-histone deacetylase (HDAC), okanye i-G protein-coupled receptors. (GPCRs)
Yena, Y., Cheng, X., Zhou, T., Li, D., Peng, J., Xu, Y., & Huang, W. (2023). I-β-Hydroxybutyrate njenge-epigenetic modifier: Iindlela eziphantsi kunye neziphumo. IHeliyon. https://doi.org/10.1016/j.heliyon.2023.e21098
Le ntsebenziswano phakathi kwe-DNA methylation kunye notshintsho lwe-histone lungundoqo ekucimeni imfuza ethile. Unxibelelwano olunjalo olucwangcisiweyo lubonisa ubunzima bolawulo lwe-epigenetic, apho iinkqubo ezininzi zisebenza kunye ukuze zilungelelanise ukubonakaliswa kwezakhi zofuzo, ekugqibeleni zibe nefuthe ekusebenzeni kweselula.
Ukuphonononga ikhonkco phakathi kweBHB kunye ne-HDAC Inhibition
Emva koko, siza kuthetha ngento ebizwa ngokuba yi-Histone Deacetylases (HDACs). Intsapho ye-HDAC iqulethe i-enzymes ezininzi, nganye ikhethwe ngamanani ahlukeneyo, njenge-HDAC1, i-HDAC2, i-HDAC3, kunye nokunye, kuquka i-HDAC5. Ezi zi-enzymes ezisusa amaqela e-acetyl kwii-histones, ezikhokelela kwi-DNA epakishwe ngokuqinileyo kunye nokunciphisa umsebenzi wemfuza.
I-BHB iboniswe ukuba inqanda i-HDAC5, kwaye oku kuye kwadibaniswa neziphumo ze-neuroprotective, njengoko kunceda ekuvimbeleni iindlela ezikhokelela ekufeni kweeseli. Oku kuye kwaphakamisa imibuzo malunga nendima yeetoni, njenge-BHB, ekuphatheni ukuphazamiseka okubandakanya ukuhlukahluka kofuzo lwe-HDAC5, njenge-bipolar disorder. Ngaba ukumodareyithwa kwe-HDAC5 ngama-ketones ibe yindlela ephambili apho ukutya kwe-ketogenic kusebenzisa iziphumo zonyango kwi-bipolar disorder?
Masibuyele kwithala lethu lethala leencwadi kunye nesifaniso soononcwadi. Yiba nomfanekiso-ngqondweni wethala leencwadi (i-epigenetics) usebenzisa i-HDACs (i-enzyme) ukupakisha iincwadi (imfuza) ngokungqongqo ngakumbi kwiishelufu (iihistones). Oku kupakishwa kuqinileyo kwiishelufu kwenza kube nzima ukukhupha iincwadi ezizimeleyo (sonke sineshelufu yeencwadi ngolu hlobo, akunjalo?). Ubunzima obufunyenwe ekukhupheni incwadi kwi-shelf kunciphisa amathuba okuba ifundwe (i-gene expression). Ii-HDAC ezimbalwa zithetha indawo eninzi kwiishelufa zeencwadi kunye nokufunyanwa lula kweencwadi (imfuza). Ndiyifumene? Kulungile! Masiqhubeke!
Kwaye abo bangenayo imvelaphi yebhayoloji, unokuzibuza ukuba i-methylation ngandlela-thile inxulumene ne-Histone Deacetylases (HDACs). Abekho. Ziindlela ezahlukeneyo ezahlukeneyo. Nangona kunjalo, zihlala zixutyushwa kunye kumanqaku afanayo kuba ezi ndlela zinobume bentsebenziswano. Iindawo ze-DNA ezifumana i-methylation enzima zinokutsala iiprotheni eziqaphela le mimandla ye-methylated. Ezi proteni zinokuthi emva koko zifune ii-HDAC kwindawo, oza kufunda ngayo kunokuba neziphumo ezinamandla.
Kwenzeka nje ukuba i-BHB idlala indima enamandla kwimodulation ye-gene expression ngokuthintela i-Histone Deacetylases (HDACs). Ukuvinjelwa kwe-BHB ye-HDACs kuthintela le deacetylation, ekhokelela kwimeko ekhululekile ye-DNA.
Ndiyazi ukuba igama elithi "ukuphumla" aliqhelekanga kulo mongo. Kodwa andikwenzi oko. Igama elithi "relaxed" kumxholo we-DNA kunye nokuguqulwa kwe-histone lifanelekile kwaye lisetyenziswa ngokuqhelekileyo kwibhayoloji yemolekyuli. Xa i-DNA "ikhululekile," ibhekisela kwimeko apho i-DNA ingaqinanga kakhulu kwi-histones. Oku kuphumla kubalulekile ekubonakalisweni kofuzo, njengoko kuvumela izinto ezikhutshelweyo kunye nezinye iiproteni ezilawulayo ukufikelela lula kwimimandla ethile ye-DNA.
Oku kuphumla kuvumela iijini ezithile, njengeFOXO3a, umzekelo, ukuba zisebenze ngakumbi. I-FOXO3a ibandakanyeka kwiinkqubo ezahlukeneyo zeselula, kubandakanywa impendulo yoxinzelelo kunye ne-apoptosis (i-programmed cell death). Ukuvinjelwa kwe-HDACs nge-BHB kunokuphucula ukubhalwa kwe-FOXO3a, igalelo ekuxhathiseni uxinzelelo lwamaselula kunye neendlela zokuphila. Esi siphumo sichaphazelekayo ngokukodwa kumxholo wokukhusela i-neuroprotection, eyona mpembelelo yonyango efunekayo kakhulu kwabo bagula ngengqondo.
Andifuni ukuba ucinge ukuba iziphumo ze-BHBs kwi-HDAC zifanelekile kuphela kwi-gene enye. Omnye umzekelo ofanelekileyo kunye nobalulekileyo wendlela ukuvinjelwa kwe-HDACs ngokubakho kweBHB njengokuguqulwa kwe-epigenetic kubonakala xa sijonga kwi-Brain-Derived Neurotrophic Factor (BDNF)
Iziphumo zethu zibonise ukuba i-ketone body BHBA inokukhuthaza ukubonakaliswa kwe-BDNF kwindawo yoxinzelelo ngaphakathi kwendawo ye-physiological (0.02-2mM) phantsi kokunikezelwa kwamandla okuqhelekileyo.
Hu, E., Du, H., Zhu, X., Wang, L., Shang, S., Wu, X., ... & Lu, X. (2018). I-Beta-hydroxybutyrate ikhuthaza ukubonakaliswa kwe-BDNF kwi-hippocampal neurons phantsi kokunikezelwa kwe-glucose eyaneleyo. Neuroscience, 386, 315-325. https://doi.org/10.1016/j.neuroscience.2018.06.036
Ukuvinjelwa kwe-BHB ye-HDACs nayo ibonakale ikhokelela ekunyuseni kwintetho ye-BDNF. I-BDNF iyimfuza ebalulekileyo yokukhula kwe-neuronal, ukusinda, kunye ne-synaptic plasticity. Ngokuthintela i-HDACs, i-BHB ikhuthaza i-acetylated state ye-histones kufuphi ne-BDNF gene, iququzelele ukubhaliswa kwayo. Oku kunyuswa kwe-BDNF kunokuba nefuthe elibalulekileyo kwi-neuroplasticity, umsebenzi wokuqonda, kunye nokunyangwa kokudakumba kunye nezinye iingxaki zengqondo.
Ukuqonda impembelelo yeBHB kwiMicroRNA Regulation
Enye indlela yolawulo lwe-epigenetic yinto ebizwa ngokuba yi-microRNAs (miRNAs), eziziimolekyuli ezincinci ze-RNA ezilawula ukubonakaliswa kofuzo. Benza njengezikhokelo ezinokuncamathisela kwisithunywa esithile se-RNA (mRNA) kwiseli, kwaye xa besenza oku, i-microRNAs (miRNAs) inokumisa umthunywa we-RNA (mRNA) ekwenzeni iiprotheni okanye ukunciphisa imveliso yeprotheni. Siyichaza njani indima ye-microRNA kwi-epigenetic expression sisebenzisa isifaniso sethu sethala leencwadi?
Kwi-analogy yethu yelayibrari yofuzo, apho iijene ziyiencwadi, kwaye ithala leencwadi limele i-epigenetics, i-microRNAs (miRNAs) zifana namanqaku amancinci afika emva kokuba unolayibrari sele ekhethe ukufunda incwadi (i-gene) kunye neefotokopi (mRNA) zenziwe. La manqaku anika isikhokelo malunga nokuba kukangaphi na umsebenzi wethala leencwadi (i-epigenetics) kufuneka aqhubeke nokufikelela kwiincwadi ezithile (imizila yemfuza) okanye nokuba ukufikelela kufuneka kubekelwe imiqathango, ukuqinisekisa ulawulo olungcono kwimbonakalo yemfuza ukuhlangabezana neemfuno zeseli.
I-BHB yandisa impembelelo yayo kwi-microRNAs (miRNAs). I-BHB yenza njani oku?Zisebenza ngokuzibophelela kwii-molecule ze-RNA (mRNA) zesithunywa, ngokuqhelekileyo kubangela ukunyanzeliswa okanye ukuthotywa kwezo zithunywa ze-RNAs. Njengoko kuchaziwe kumzekeliso wethu wethala leencwadi, ii-microRNAs (i-miRNAs) zidlala indima kulawulo lwasemva kokukhutshelwa ngokubhala ngokusisiseko ngokucokisekileyo ukuchazwa kofuzo. Basenokujolisa kwii-RNAs zomthunywa (mRNAs) wokuthotywa okanye ukuthintela ukuguqulelwa kwabo ukwandisa okanye ukunciphisa ukuveliswa kweeprotheni ezithile ekuphenduleni iimfuno zeseli.
Iinkqubo ezinjalo ziyinxalenye ebalulekileyo yommiselo emva kokubhala okuchaphazela uluhlu olubanzi lweenkqubo zeselula, ezenzekayo ukubandakanya imetabolism.
Izifundo ezenziwe kumavolontiya abantu zibonise ukuba iiprofayili zokubonisa i-microRNA zatshintshwa kakhulu emva kwe-regimen ye-6 yeveki kwi-Ketogenic Diet (KD), ebonisa ukuba utshintsho lwe-metabolic olubangelwa yi-KD, olubandakanya amanqanaba aphezulu e-BHB, lunokubangela utshintsho kwi-miRNA. intetho.
Lilonke, amavolontiya akwi-KD abonise ukulawulwa kwe-miRNAs ejolise kuhlobo oluthile oludityaniswe kwimetabolism yezondlo kunye ne-mTOR, ii-PPARs, i-insulin, kunye neendlela zokubonisa i-cytokine.
Nasser, S., Vialichka, V., Biesiekierska, M., Balcerczyk, A., & Pirola, L. (2020). Iziphumo zokutya kwe-ketogenic kunye nemizimba ye-ketone kwinkqubo ye-cardiovascular system: Imicimbi yokugxila. Ijenali yehlabathi yesifo seswekile, i-11 (12), i-584-595. https://doi.org/10.4239/wjd.v11.i12.584
Kodwa inxalenye enomdla yayiyeyokuba i-miRNAs elawulwa yi-Ketogenic Diet (KD) ijolise kwiijini ezithile ezidityaniswe ne-metabolism yezondlo, kunye neendlela ezibalulekileyo zokubonisa iimpawu ezifana ne-mTOR (i-mechanistic target ye-rapamycin), i-PPARs (i-peroxisome proliferator-activated receptors), i-insulin. umqondiso, kunye neendlela zokubonisa i-cytokine. Ezi ziindlela ezibalulekileyo kwimpilo yengqondo ngokumodareyitha i-metabolism yamandla kunye nokulungisa kunye nokunciphisa i-neuroinflammation.
Ngenye indlela i-BHB enokuthi ifake ngayo igalelo ekulungiseni kakuhle ukubonakaliswa kwemfuza, ukuchaphazela umsebenzi weselula, kunye nokubonelela ngemiphumo enokubakho yonyango kwiinkqubo zesifo okanye i-metabolic states.
isiphelo
Kule nqaku, uhlolisise iindlela ezininzi apho ubukho beBHB busebenza njengemodyuli ye-epigenetic ye-gene expression. Ukubuyela kwisifaniso sethu selayibrari egcwele iincwadi (i-genes) kunye nomgcini-zincwadi (epigentics), kuyacaca ukuba iBHB ithatha indima yomgcini-zincwadi "kwithala leencwadi" lethu.
Ngokufana nempembelelo yomgcini-zincwadi kwimixholo yethala leencwadi, i-BHB ayitshintshi i-DNA esisiseko ukulandelelana ngokwayo; ishiya ulandelelwano lwe-DNA lungatshintshanga. Nangona kunjalo, i-BHB idlala indima ebalulekileyo ekuphembeleleni amanqaku e-epigenetic kunye neenkqubo ze-molecular ezimisela i-gene expression. Ngempembelelo yayo kwiinkqubo ezifana nokuguqulwa kwe-histone, i-DNA methylation, kunye nokulawulwa kwe-microRNA, i-BHB ivela njengomlawuli onamandla kwihlabathi eliyinkimbinkimbi ye-epigenetics. Ichaphazela kakhulu imeko yethu yemetabolism kwaye inokuchaphazela ukubonakaliswa kofuzo, kuphembelela ukusebenza kweenkqubo ezininzi ezifanelekileyo ezichaphazela impilo yengqondo. Kwaye ke ndiyabuza, kutheni ingaboneleli ngeziphumo zonyango kwizigulo zengqondo kunye nokuphazamiseka kwemithambo-luvo?
Ndiyathemba ngokunyanisekileyo ukuba eli nqaku libe luncedo ekuqondeni kwakho ukutya kwe-ketogenic. Unelungelo lokwazi zonke iindlela onokuziva ungcono ngazo, kunye nefuthe elinamandla lokubonakaliswa kwee-ketones ezichongiweyo kwiincwadi zophando, unokufumanisa ukuba ukutya kwe-ketogenic kungenye yazo.
Ucaphulo
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Hu, E., Du, H., Zhu, X., Wang, L., Shang, S., Wu, X., Lu, H., & Lu, X. (2018). I-Beta-hydroxybutyrate Ikhuthaza ukubonakaliswa kwe-BDNF kwi-Hippocampal Neurons phantsi kwe-Supply yeGlucose eyaneleyo. Neuroscience, 386, 315-325. https://doi.org/10.1016/j.neuroscience.2018.06.036
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Mikami, D., Kobayashi, M., Uwada, J., Yazawa, T., Kamiyama, K., Nishimori, K., … & Iwano, M. (2019). I-β-Hydroxybutyrate, umzimba we-ketone, inciphisa umphumo we-cytotoxic we-cisplatin ngokusebenza kwe-HDAC5 kwiiseli ze-renal cortical epithelial. Iinzululwazi zoBomi, 222, 125-132. https://doi.org/10.1016/j.lfs.2019.03.008
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Nasser, S., Vialichka, V., Biesiekierska, M., Balcerczyk, A., & Pirola, L. (2020). Iziphumo zokutya kwe-ketogenic kunye nemizimba ye-ketone kwinkqubo ye-cardiovascular system: Imicimbi yokugxila. Ijenali yeHlabathi yeSifo seswekile, 11(12), 584-595. https://doi.org/10.4239/wjd.v11.i12.584
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