Litlamorao le mesebetsi ea urolithin A ke efe? Ke lihlahisoa life tse kenyelletsoeng

 Urolithin A ke ntho ea bohlokoa ea bioactive e sebelisoang haholo meriana le tlhokomelo ea bophelo bo botle. Ke enzyme haholo-holo e hlahisoang ke liphio 'me e na le mosebetsi oa ho qhaqha maqeba a mali. Litlamorao le mesebetsi ea boselamose ea Urolithin A li bonts'oa haholo likarolong tse latelang.

Urolithin A e thibela ho senyeha ha mesifa

1. Khothaletsa motsoako oa liprotheine tsa mesifa le ho kenya tšebetsong tsela ea pontšo ea mTOR

Sepheo sa mammalian sa rapamycin (mTOR) tsela ea pontšo ke tsela e ka sehloohong ea ho laola motsoako oa liprotheine tsa mesifa. Urolithin A e ka kenya tšebetsong tsela ea ponts'o ea mTOR le ho khothaletsa protheine synthesis liseleng tsa mesifa.

mTOR e khona ho utloa matšoao a kang limatlafatsi le lintlha tsa ho hōla liseleng. Ha e kentsoe, e tla qala letoto la limolek'hule tsa matšoao a tlase, joalo ka ribosomal protein S6 kinase (S6K1) le eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Urolithin A e kenya tshebetsong mTOR, phosphorylating S6K1 le 4E-BP1, ka tsela eo e kgothalletsa qalo ya phetolelo ya mRNA le kopano ya ribosome, le ho akofisa protheine synthesis.

Ka mohlala, litekong tsa lisele tsa mesifa tse nang le in vitro cultured, ka mor'a ho eketsa urolithin A, ho ile ha hlokomeloa hore litekanyetso tsa phosphorylation tsa mTOR le limolek'hule tsa eona tse tlaase li ile tsa eketseha, 'me polelo ea li-protein synthesis markers (tse kang ketane e boima ea myosin) e ile ea eketseha.
E laola maikutlo a qotsitsoeng ka mokhoa o ikhethileng oa mesifa

Urolithin A e ka laola polelo ea lintlha tse ngotsoeng ka mokhoa o ikhethileng oa mesifa tse bohlokoa bakeng sa motsoako oa protheine ea mesifa le phapang ea lisele tsa mesifa. Ka mohlala, e ka laola polelo ea myogenic differentiation factor (MyoD) le myogenin.

MyoD le Myogenin li ka khothalletsa ho arohana ha lisele tsa mesifa ea mesifa ho lisele tsa mesifa le ho kenya tšebetsong polelo ea liphatsa tsa lefutso tse khethehileng tsa mesifa, ka tsela eo ho khothalletsa motsoako oa liprotheine tsa mesifa. Setšoantšong sa atrophy ea mesifa, ka mor'a phekolo ea urolithin A, polelo ea MyoD le Myogenin e ile ea eketseha, e thusang ho boloka mesifa ea mesifa le ho thibela ho fokotseha ha mesifa.

2. Thibela ho senyeha ha protheine ea mesifa le ho thibela tsamaiso ea ubiquitin-proteasome (UPS)

UPS ke e 'ngoe ea litsela tse ka sehloohong tsa ho senyeha ha protheine ea mesifa. Nakong ea mesifa ea mesifa, li-ligase tse ling tsa E3 ubiquitin, tse kang mesifa ea atrophy F-box protein (MAFbx) le mesifa ea RING finger protheine 1 (MuRF1), e sebelisoa, e ka tšoaeang liprotheine tsa mesifa ka ubiquitin ebe e li senya ka proteasome.

Urolithin A e ka thibela polelo le ts'ebetso ea li-ligase tsena tsa E3 ubiquitin. Litekong tsa mehlala ea liphoofolo, urolithin A e ka fokotsa maemo a MAFbx le MuRF1, ea fokotsa letšoao la ho ata ha liprotheine tsa mesifa, kahoo e thibela ho senyeha ha liprotheine tsa mesifa ea UPS-mediated le ho thibela ka katleho ho fokotseha ha mesifa.

Ho feto-fetoha ha tsamaiso ea autophagy-lysosomal (ALS)

ALS e phetha karolo ea ho nchafatsa liprotheine tsa mesifa le li-organelles, empa ho sebetsa ho feteletseng ho ka boela ha lebisa ho fokotseng mesifa. Urolithin A e ka laola ALS ho isa boemong bo loketseng. E ka thibela autophagy e feteletseng le ho thibela ho senyeha ho feteletseng ha liprotheine tsa mesifa.
Ka mohlala, urolithin A e ka laola polelo ea liprotheine tse amanang le autophagy (tse kang LC3-II), e le hore e ka boloka homeostasis ea tikoloho ea lisele tsa mesifa ha e ntse e qoba ho tlosoa ho feteletseng ha liprotheine tsa mesifa, kahoo e thusa ho boloka mesifa ea mesifa.

3. Ntlafatsa metabolism ea matla ea lisele tsa mesifa

Ho honyela ha mesifa ho hloka matla a mangata, 'me mitochondria ke sebaka se seholo sa tlhahiso ea matla. Urolithin A e ka ntlafatsa ts'ebetso ea mesifa ea mitochondria le ho ntlafatsa katleho ea tlhahiso ea matla. E ka khothaletsa biogenesis ea mitochondrial mme ea eketsa palo ea mitochondria.

Ka mohlala, urolithin A e ka kenya tšebetsong receptor ea peroxisome proliferator-activated γ coactivator-1α (PGC-1α), e leng molaoli ea ka sehloohong oa mitochondrial biogenesis, e khothalletsang ho pheta-pheta ha DNA ea mitochondrial le motsoako oa liprotheine tse amanang. Ka nako e ts'oanang, urolithin A e ka boela ea ntlafatsa ts'ebetso ea ketane ea phefumoloho ea mitochondrial, ea eketsa motsoako oa adenosine triphosphate (ATP), ea fana ka matla a lekaneng bakeng sa ho fokotseha ha mesifa, le ho fokotsa ho fokotseha ha mesifa ho bakoang ke matla a sa lekaneng.

E laola metabolism ea tsoekere le lipid mme e tšehetsa tšebetso ea mesifa

Urolithin A e khona ho laola tsoekere le lipid metabolism ea lisele tsa mesifa. Mabapi le metabolism ea tsoekere, e ka ntlafatsa ho amoheloa le ho sebelisoa ha tsoekere ke lisele tsa mesifa, le ho netefatsa hore lisele tsa mesifa li na le likaroloana tse lekaneng tsa matla ka ho kenya tšebetsong tsela ea pontšo ea insulin kapa litsela tse ling tse amanang le ho tsamaisa tsoekere.

Mabapi le metabolism ea lipid, urolithin A e ka khothaletsa oxidation ea acid e mafura, e fana ka mohloli o mong oa matla bakeng sa ho honyela ha mesifa. Ka ho matlafatsa metabolism ea tsoekere le lipid, urolithin A e boloka matla a lisele tsa mesifa mme e thusa ho thibela ho theoha ha mesifa.

Urolithin A e ntlafatsa metabolism

1. Laola metabolism ea tsoekere le ho ntlafatsa kutloisiso ea insulin
Urolithin A e ka ntlafatsa kutloisiso ea insulin, e leng bohlokoa ho boloka botsitso ba tsoekere maling. E ka sebetsa ho limolek'hule tsa bohlokoa tse tseleng ea pontšo ea insulin, joalo ka liprotheine tsa insulin receptor substrate (IRS).

Boemong ba ho hanyetsa insulin, tyrosine phosphorylation ea protheine ea IRS e ea thibeloa, e leng se bakang ho hloleha ha tsela ea pontšo ea phosphatidylinositol 3-kinase (PI3K) e tlase ho sebetsa ka mokhoa o tloaelehileng, mme karabelo ea sele ho insulin ea fokola.

Urolithin A e ka khothaletsa tyrosine phosphorylation ea protheine ea IRS, ka hona ea kenya tšebetsong tsela ea pontšo ea PI3K-protein kinase B (Akt), e nolofalletsa lisele ho monya le ho sebelisa tsoekere hamolemo. Ka mohlala, litekong tsa mohlala oa liphoofolo, ka mor'a ho tsamaisoa ha urolithin A, kutloisiso ea mesifa le lisele tsa adipose ho insulin e ile ea ntlafatsoa haholo, 'me maemo a tsoekere ea mali a laoloa ka katleho.

E laola sebopeho sa glycogen le ho senyeha

Glycogen ke mofuta oa mantlha oa polokelo ea tsoekere 'meleng, e bolokiloeng haholo sebeteng le liseleng tsa mesifa. Urolithin A e khona ho laola ho qaptjoa le ho bola ha glycogen. E ka kenya tšebetsong glycogen synthase, ea khothaletsa tlhahiso ea glycogen, 'me ea eketsa polokelo ea glycogen.

Ka nako e ts'oanang, urolithin A e ka boela ea thibela ts'ebetso ea li-enzyme tsa glycogenolytic, joalo ka glycogen phosphorylase, 'me ea fokotsa bongata ba glycogen e qhibilihang ho ba tsoekere ebe e lokolloa maling. Sena se thusa ho tsitsisa maemo a tsoekere ea mali le ho thibela ho fetoha ho feteletseng ha tsoekere ea mali. Phuputsong ea mohlala oa lefu la tsoekere, ka mor'a phekolo ea urolithin A, litaba tsa glycogen sebeteng le mesifa li ile tsa eketseha, 'me taolo ea tsoekere ea mali e ile ea ntlafatsoa.

2. Ntlafatsa metabolism ea lipid le ho thibela motsoako oa mafura a mafura

Urolithin A e na le phello e thibelang tšebetsong ea lipid synthesis. Sebeteng le liseleng tsa adipose, e ka thibela li-enzyme tsa bohlokoa ka har'a motsoako oa mafura a acid, joalo ka fatty acid synthase (FAS) le acetyl-CoA carboxylase (ACC).

FAS le ACC ke li-enzyme tsa bohlokoa tsa taolo ho de novo synthesis ea mafura acid. Urolithin A e ka fokotsa tlhahiso ea li-acid tse mafura ka ho thibela tšebetso ea tsona. Ka mohlala, ka mohlala oa sebete sa mafura a bakoang ke lijo tse nang le mafura a mangata, urolithin A e ka fokotsa ts'ebetso ea FAS le ACC sebeteng, ea fokotsa motsoako oa triglycerides, 'me kahoo ea fokotsa ho bokellana ha lipid sebeteng.

E khothalletsa oxidation ea mafura a mafura

Ntle le ho thibela motsoako oa acid e mafura, urolithin A e ka boela ea khothalletsa ho bola ha oxidative ea mafura a acid. E ka kenya tšebetsong litsela tsa matšoao le li-enzyme tse amanang le oxidation ea mafura a acid. Ka mohlala, e ka phahamisa mosebetsi oa carnitine palmitoyltransferase-1 (CPT-1).

CPT-1 ke enzyme ea bohlokoa ho mafura a acid β-oxidation, e ikarabellang bakeng sa ho tsamaisa mafura a acid ho mitochondria bakeng sa ho bola ha oxidative. Urolithin A e khothalletsa β-oxidation ea mafura a acid ka ho kenya CPT-1, e eketsa tšebeliso ea matla a mafura, e thusa ho fokotsa ho boloka mafura a 'mele, le ho ntlafatsa metabolism ea lipid.

3. Ntlafatsa metabolism ea matla le ho ntlafatsa mosebetsi oa mitochondrial

Mitochondria ke "lifektheri tsa matla" tsa lisele, 'me urolithin A e ka ntlafatsa ts'ebetso ea mitochondria. E ka laola biogenesis ea mitochondrial le ho khothaletsa motsoako oa mitochondrial le nchafatso. Ka mohlala, e ka kenya tšebetsong peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α).

PGC-1α ke molaoli ea ka sehloohong oa biogenesis ea mitochondrial, e ka khothalletsang ho ikatisa ha DNA ea mitochondrial le motsoako oa liprotheine tse amanang le mitochondrial. Urolithin A e eketsa palo le boleng ba mitochondria mme e ntlafatsa katleho ea tlhahiso ea matla ea lisele ka ho kenya tšebetsong PGC-1α. Ka nako e ts'oanang, urolithin A e ka boela ea ntlafatsa ts'ebetso ea ketane ea phefumoloho ea mitochondria le ho eketsa motsoako oa adenosine triphosphate (ATP).

4. Ho laola Reprogramming ea Metaboliki ea Lisele

Urolithin A e ka tataisa lisele hore li kenelle tšebetsong ea metabolic, e leng ho etsang hore metabolism ea sele e sebetse hantle haholoanyane. Tlas'a maemo a itseng a khatello ea maikutlo kapa lefu, mokhoa oa metabolism oa sele o ka fetoha, e leng se bakang ho fokotseha ha ts'ebetso ea tlhahiso ea matla le ho kopanya lintho.

Urolithin A e ka laola litsela tsa matšoao a metabolic liseleng, joalo ka AMP-activated protein kinase (AMPK) tsela ea pontšo. AMPK ke "sensor" ea metabolism ea matla a cellular. Ka mor'a hore urolithin A e sebetse AMPK, e ka etsa hore lisele li fetohe ho tloha ho anabolism ho ea ho catabolism, ho sebelisa matla le limatlafatsi ka katleho, kahoo ho ntlafatsa ts'ebetso ea metabolism ka kakaretso.

Tšebeliso ea urolithin A ha e felle feela lefapheng la bongaka. Hape butle-butle e fumana tlhokomelo lihlahisoa tsa bophelo bo botle le litlolo. Urolithin A e kenyelletsoa lihlahisoa tse ngata tsa bophelo bo botle ho matlafatsa tšireletso ea 'mele, ho ntlafatsa phallo ea mali le ho khothalletsa metabolism. Hangata lihlahisoa tsena li na le li-capsules, matlapa kapa metsi, tse loketseng litlhoko tsa lihlopha tse fapaneng tsa batho.

Lefapheng la litlolo, urolithin A e sebelisoa haholo lihlahisoa tsa tlhokomelo ea letlalo ka lebaka la ho tsosolosoa ha lisele le thepa ea ho thibela botsofali. E ka ntlafatsa phallo ea mali letlalong 'me ea khothalletsa motsoako oa collagen, ka tsela eo, e ntlafatsa letlalo le khanyang. Mefuta e mengata ea maemo a holimo ea tlhokomelo ea letlalo e se e qalile ho sebelisa urolithin A e le motsoako oa mantlha ho qala lihlahisoa tse thibelang botsofali, ho lokisa le ho nosetsa ho kopana le takatso ea bareki ea letlalo le letle.

Qetellong, e le ntho ea bioactive e nang le mesebetsi e mengata, urolithin A e bontšitse tebello e pharaletseng ea ts'ebeliso litabeng tsa meriana, tlhokomelo ea bophelo bo botle le botle. Ka ho teba ha lipatlisiso tsa mahlale, sebaka sa ts'ebeliso ea urolithin A se tla tsoela pele ho hola, ho fana ka likhetho tse ngata bakeng sa bophelo bo botle le botle ba batho.