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Uninzi lwezifundo ze-metabolic kwiimpuku ziqhutywa kubushushu begumbi, nangona ziphantsi kwezi meko, ngokungafaniyo nabantu, iimpuku zichitha amandla amaninzi. Apha, sichaza ubunzima obuqhelekileyo kunye nokutya okuzifuzisiweyo Iimpuku zabekwa kangangeentsuku ezingama-33 ze-22, 25, 27.5 ne-30 ° C. Kwinkqubo ye-calolorimsela engathanga ngqo. Sibonisa ukuba inkcitho yamandla inyuka ngokusuka kwi-30 ° C ukuya kwi-22 ° C kwaye malunga ne-30% ephezulu nge-22 ° C kwimodeli yemouse. Kwiimpuku ezithile eziqhelekileyo, ukutya okutyayo zibaliwe. Kwelinye icala, iimpuku zedio azinciphisi ukutya xa ihlile. Ke, ekupheleni kwesifundo, iimpuku nge-30 ° C yayinomzimba ophakamileyo, i-DATES kunye nePlasma Glycerol kunye nePlasma Glycerol kunye ne-trchlolcerol kunye ne-triglycerol kunye neempuku nge-MNGE nge-MNGE nge-MNGE nge-MNGE nge-MNGE. Ukungalingani kwiimpuku zedio kunokubangelwa kukutya okusekwe ngokuzonwabisa.
Imouse yeyona mfuziselo yesilwanyana isetyenziswayo yokufundwa kwequlokholi-moya kunye ne-pathophysiology, kwaye ihlala isilwanyana esingagqibekanga esisetyenziselwa ukufumanisa iziyobisi kunye nophuhliso. Nangona kunjalo, iimpuku zahlukile ebantwini ngeendlela ezibalulekileyo zomzimba, kwaye ngelixa iAdmetric Sciction ingasetyenziselwa ukuguqulela abantu, umahluko omkhulu phakathi kweempuku kwaye abantu balele kwi-themostas of kunye namandla e-celecostas. Oku kubonisa ukungahambelani. Ubunzima obuqhelekileyo beempuku zabantu abadala bungaphantsi kwamawakawaka amaxesha amancinci (i-50 g vs. . I-Equation 2. Ngenxa yoko, iimpuku ziphulukana nobungangamsha obungaphezulu komthamo wabo, ke zinovelwano ngakumbi kubushushu, kwaye zine-shority metalmia izihlandlo ezilishumi ngaphezulu koko. Kumaqondo obushushu egumbi (~ 22 °), iimpuku kufuneka zandise inkcitho yazo iyonke (i-EE) malunga ne-30% ukugcina ubushushu bomzimba ophambili. Kwiqondo lobushushu elisezantsi, i-EE inyuka ngakumbi malunga ne-50% ne-100% nge-15 ne-7 ° C ngokuthelekiswa ne-EE nge-22 ° C. Ke, iimeko zezindlu ezisemgangathweni zikhupha impendulo yoxinzelelo olubandayo, olunokulalanisa kakhulu kwimouse ezivela ebantwini, njengabantu abaphila kwixesha labo kwiimeko ze-thermolution (kuba indawo yethu esezantsi i-suble inobuthathaka Iqondo lokushisa, njengoko senza indawo ye-thermontels (Tnz) esijikeleze i-US. Ee Eas ~ 19 ukuya kwi-30 ukuya kwi-30 ukuya kwi-30 ° C6, ngelixa iimpuku zine-mice ne Iqela elincinci liyi-2-4 i-C7,8 enyanisweni, le nkalo ibalulekileyo ifumene ingqwalaselo ebonakalayo kwiminyaka yakutshanje, i-7,11,11,11,11,11,11,11, iphakanyisiwe Ngokwandisa ubushushu be-shell 9. Nangona kunjalo, akukho mvumelwano kuluhlu lobushushu olubonisa ubunyani be-thermonetporalution eneempuku. Thus, whether the lower critical temperature in the thermoneutral range in single-knee mice is closer to 25°C or closer to 30°C4, 7, 8, 10, 12 remains controversial. I-EE kunye nezinye iiparamitha ze-metabolic zinqunyelwe kwiiyure nje ukuya kwiintsuku, ngoko ke ukuvezwa kwexesha elide kubushushu obahlukeneyo kunokuchaphazela iiparamitha ze-metabolic ezifana nobunzima bomzimba azicacanga. Ukusetyenziswa, ukusetyenziswa komhlaba, ukunyamezelana kweglucose, kunye ne-plasma liipi kunye ne-glucose yoxinizelelo kunye ne-Houtite-elawula iihomoni. Ukongeza, kuya kufuneka ngakumbi ukuqiniseka ukuba ukutya kunokuphembelela kangakanani na le parameter (i-dio mice ekutsaleni enamafutha aphezulu inokuziswa ngakumbi kwi-Youle-esekwe). Ukubonelela ngolwazi oluthe kratya ngesi sihloko, sihlolisise isiphumo sokukhulisa ubushushu be-metanlical ye-metablic esele i-Aby-Fouremes ye-Mure-Figs ye-Ader. Iimpuphu zigcinwe ngo-22, 25, 27.5, okanye i-30 ° C ubuncinci iiveki ezintathu. Amaqondo obushushu angaphantsi kwe-22 ° C engakhange afungiwe kuba izindlu ezisemgangathweni ezisemgangathweni aziqhelekanga ngaphantsi kobushushu begumbi. Sifumanise ukuba ubunzima obuqhelekileyo kunye ne-Dio Share i-dio dice iphendule ngokufanayo kutshintsho kubushushu be-evaled ngokwe-EE nakubathathi cala okanye ngaphandle kwendawo yokuhlala / ngaphandle kwempahla yendawo yokuhlala / i-velles). Nangona kunjalo, ngelixa iimpuku eziqhelekileyo zihlengahlengise ukutya kwazo ngokwe-EE, ukutya kweempuku zedio kwakuzimele kakhulu kwi-EE, kukhokelela kwiimpuku ezifumana ubunzima ngakumbi. Ngokwedatha yobunzima bomzimba, ukugxininiswa kweplasma ze-lipids kunye namaqumrhu e-Ketone kubonise ukuba i-DIO MICE NGE-30 ° C wayenelungelo lokungazithembi ngakumbi kune-MNGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-MAGE nge-M. Izizathu eziphantsi komahluko ekulinganiselwe amandla kunye ne-EE phakathi kobunzima obuqhelekileyo kunye ne-dio mice ifuna ukuqhubeka notshintsho, kodwa zinokuhambelana notshintsho olusekwe kwi-DIO kunye nesiphumo sokutya okusekwe kumnandi.
I-EE inyuke nge-30 ukuya kwi-22 ° C kwaye yayimalunga ne-30% iphezulu nge-22 ° C ngokuthelekiswa ne-30 ° C ngokuthelekiswa ne-30 ° C (Fig. 1A, b). Inqanaba lokuphefumla lokuphefumla (rer) lalizimele kubushushu (umzobo 1c, d). Ukutya ukutya bekungqinelana ne-EE Dynamics kwaye inyuke ngeqondo lokushisa (kunye ne-30% ephezulu nge-22 ° C) I-CART i-30 ° C. I-1g). -To).
Iimpuku ezingamadoda (c57bl / 6j, iiveki ezingama-20 ubudala, indlu nganye, n = 7) zazigcinwe kwi-Metabolic City Cred nge-22 ° C. Kwiveki enye ngaphambi kokuqala kwesifundo. Iintsuku ezimbini emva kokuqokelelwa kwedatha yangasemva, iqondo lobushushu lakhuliswa kwi-2 ° Cunch nge-06: 00 iiyure ngosuku (ukuqala kwesigaba sokukhanya). Idatha inikezelwa njenge-± Impazamo ye-± yentsingiselo, kunye nenqanaba elimnyama (18: 00-06: 00 h) limelwe yibhokisi engwevu. Inkcitho yamandla (i-KCal / H), inkcitho yenkcitho yezakhono kwiqondo lokuhlala (i-KCal / 24 h (Ixabiso le-zero lichazwa njenge-0,7). I-Eumulating yokutya (g), F 24H iyonke, g 24h iyonke i-subike ). Iimpuku zigcinwa kubushushu obubonisiweyo iiyure ezingama-48. Idatha eboniswe nge-24, 26, 28 ne-30 ° C ijonga kwiiyure ezingama-24 zokugqibela zomjikelo ngamnye. Iigundane zihlala zondlekile kwisifundo sonke. Intsingiselo yeenkcukacha-manani yavavanywa ngemilinganiselo ephindaphindiweyo ye-anova enye elandelwa luvavanyo lweTukey. I-Asterisks ibonisa ukubaluleka kwexabiso lokuqala lama-22 ° C, ishayini ibonisa ukubaluleka phakathi kwamanye amaqela njengoko kubonisiwe. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,0001. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,0001. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001.Amaxabiso aphakathi abalwa lonke ixesha lovavanyo (0-192 iiyure). n = 7.
Njengakwimeko yeempuku ezithile eziqhelekileyo, i-EE inyuke ngeqondo lokushisa, kwaye kule meko, i-EE ikwamalunga ne-30% iphezulu nge-22 ° C ngokuthelekiswa ne-30 ° C ngokuthelekiswa ne-30 ° C (fic. 2a, b). URer akazange atshintshe kubushushu obahlukeneyo (Fig. 2c, D). Ngokwahlukileyo kwiimpuku eziqhelekileyo eziqhelekileyo, ukutya ukutya kwakungangqinelani ne-EE njengomsebenzi wobushushu begumbi. Ukutya ukutya, ukuthathwa kwamanzi, kunye nenqanaba lomsebenzi bebezimele kubushushu (amakhiwane. 2E-J).
Indoda (c57bl / 6J, iiveki ezingama-20) iimpuku zikaDio bezigcinwe kwi-Metabolic City Cred Creds nge-22 ° C. Kanga kwiveki enye ngaphambi kokuqala kwesifundo. Iimpuku zinokusebenzisa i-45% HFD Litlid. Emva kokwamkelwa kweentsuku ezimbini, idatha yesiseko yaqokelelwa. Emva koko, amaqondo obushushu akhuliswa kwii-2 ° C nge-2 00 ngentsimbi ye-06: 00 (ukuqala kwesigaba sokukhanya). Idatha inikezelwa njenge-± Impazamo ye-± yentsingiselo, kunye nenqanaba elimnyama (18: 00-06: 00 h) limelwe yibhokisi engwevu. Inkcitho yamandla (i-KCal / H), inkcitho yenkcitho yezakhono kwiqondo lokuhlala (i-KCal / 24 h (Ixabiso le-zero lichazwa njenge-0,7). I-Eumulating yokutya (g), F 24H iyonke, g 24h iyonke i-subike ). Iimpuku zigcinwa kubushushu obubonisiweyo iiyure ezingama-48. Idatha eboniswe nge-24, 26, 28 ne-30 ° C ijonga kwiiyure ezingama-24 zokugqibela zomjikelo ngamnye. Iimpuku zigcinwa nge-45% hfd kude kube sekupheleni kwesifundo. Intsingiselo yeenkcukacha-manani yavavanywa ngemilinganiselo ephindaphindiweyo ye-anova enye elandelwa luvavanyo lweTukey. I-Asterisks ibonisa ukubaluleka kwexabiso lokuqala lama-22 ° C, ishayini ibonisa ukubaluleka phakathi kwamanye amaqela njengoko kubonisiwe. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * ઇ than <0,05, *** р <0,001, **** р <0 ~ 0,0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * ઇ than <0,05, *** р <0,001, **** р <0 ~ 0,0001. * P <0.05, *** p <0.001, **** p <0.0001.Amaxabiso aphakathi abalwa lonke ixesha lovavanyo (0-192 iiyure). n = 7.
Kolunye uthotho lweemvavanyo, sihlolisise isiphumo seqondo lobushushu le-parameter efanayo, kodwa ngeli xesha phakathi kwamaqela eempuku ezazigcinwa rhoqo kubushushu obuthile. Iimpuku zahlulahlulwa zangamaqela amane ukunciphisa utshintsho oluthile kwezibalo kwintsingiselo kunye nokuphambuka komgangatho wobunzima bomzimba, amanqatha, kunye nobunzima bomzimba oqhelekileyo (Fig. 3a-c). Emva kweentsuku ezisi-7 zokunyuswa, kwiintsuku ezi-4 ze-EE zabhalwa. I-EE ichaphazeleke kakhulu kubushushu obufanelekileyo phakathi kwemini yemini kwaye ebusuku (Fig. Xa kuthelekiswa namanye amaqela, i-RER yeqela lama-25 le-25 lancitshiswa, kwaye kwakungekho maqela aphakathi kwamaqela aseleyo (Fig. 3F, G). Ukutya kukutya kwiphethini ye-EE inyuke malunga ne-30% nge-22 ° xa kuthelekiswa ne-30 ° C (Fig. 3h, i). Ukusetyenziswa kwamanzi kunye namanqanaba omsebenzi awafani kakhulu phakathi kwamaqela (i-3J, k). Ukuvezwa kwamaqondo obushushu ahlukeneyo ukuya kuthi ga kwiintsuku ezingama-33 akukhokeli kwi-messies ngobunzima bomzimba, ubunzima obungaphezulu, kodwa baphumela ekunciphiseni ubunzima bomzimba we-15% xa kuthelekiswa amanqaku ozinzileyo (umzobo.-s). I-3b, R, C) Ngelishwa, iKhabhinethi eyi-30 ° 9 ineempazamo zokulinganisa kwaye azinakubonelela ngedatha echanekileyo ye-EE kunye ne-ReR.
- ubunzima bomzimba (a), ubunzima obuncindi (b) kunye nobunzima obuyinqatha (c) emva kweentsuku ezisi-8 (ngenye imini ngaphambi kwenkqubo yeSoby). D I-DROFITION YOKUXELWA (I-KCal / H). I-Endipetion ephakathi kwamandla (0-108 iiyure) kubushushu obahlukeneyo (i-KCAL / iiyure ezingama-24). F I-DREPRIRATORTRATOTOROTOR TRATIONATIONATO (Rer) (i-VCO2 / VO2). g Ithetha i-rer (i-VCO2 / VO2). H itoti yokutya (g). Ndithetha ukutya okutyayo (G / iiyure ezingama-24). j Iyonke yokusetyenziswa kwamanzi (ml). k ophakathi ukusebenzisa amanzi (ml / 24 h). Inqanaba lomsebenzi owodwa (m). Inqanaba lomsebenzi (m / 24 h). n Ubunzima bomzimba ngomhla we-18, o Guqula ubunzima bomzimba (ukusuka kwi-18 ukuya kwi-18 ka-Pight ukuya kumhla we-18, ukusuka kwi-18 ka-Right ukuya kumhla we-18 , kwaye utshintshe ubunzima obunamafutha (ukusuka kwiintsuku ezingama-18 ukuya kwi-18). Ukubaluleka kwenkcukacha-manani kumanyathelo aphindaphindiweyo kwavavanywa kwe-One-Anova elandelwa luvavanyo lweTukey. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001. * P <0,05, ** p <0,01, *** p <0,001, **** p <0,0001. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001. * P <0,05, ** p <0,01, *** p <0,001, **** p <0,0001. * P <0.05, ** p <0.01, *** p <0.001, **** p <0.0001.Idatha inikezelwa njenge-Foble + Impazamo esemgangathweni yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe ziibhokisi ezingwevu. Amachaphaza kwi-fistograms abonisa iimpuku zomntu ngamnye. Ixabiso eliphakathi labalwa lonke ixesha lovavanyo (0-108). n = 7.
Iimpuku zihambelana nobunzima bomzimba, ubunzima obuninzi, kunye nobunzima be-4, 25, 27.5, kunye ne-30 ° C njengeempuku eziqhelekileyo zeempuku. . Xa uthelekisa amaqela eempuku, ubudlelwane phakathi kwe-EE kunye neqondo lokushisa lubonise ubudlelwane obufanayo obufanayo nobushushu ngokuhamba kwexesha kwiimpuku ezifanayo. Ke, iimpuku zigcinwe nge-22 ° Cuted malunga ne-30% yamandla ngakumbi kune-mice kwi-30 ° C (Fig. 4D, e). Xa ukufunda imiphumo kwizilwanyana, ubushushu ayisoloko ichaphazela i-rer (Fig. 4F, G). Ukutya, ukutya kwamanzi, kunye nomsebenzi wawungachaphazeleka kakhulu kubushushu (amakhiwane. I-4h-M). Emva kweentsuku ezingama-33 zokukhulisa, iimpuku nge-30 ° C yayinomzimba ophezulu kakhulu kuneempuku nge-22 ° C (Fig. 4N). Xa kuthelekiswa namanqaku abo asisiseko abo, iimpuku zakhulisa kwi-30 ° C yayinamatye emigudu ephezulu kakhulu kuneempuku zayakhuliswa nge-22 ° C (intsingiselo) Ukuzifumana ubunzima obuphezulu kukubangelwa kukunyuka kobuninzi (umzobo 4p, q) kunokuba unyuswe ubunzima obunqindi (Fig. 4R, s). Ihambelana nexabiso eliphantsi le-EE nge-30 ° C, intetho yeentlobo ezahlukeneyo ze-Bit onyusa umsebenzi / umsebenzi we-ADROXI THISTE 22 ° C: ADRA16, NO-ADRM16. Ezinye izinto eziphambili ezenza ukuba umsebenzi we-BIT / umsebenzi awuchaphazelekanga: i-sema3a (i-nerrachondul biogenesis), i-TFRB1, ADRA2A, PLUTH1 Ngokumangalisayo, i-UCP1 kunye neVegf-A, enxulumene nokunyuka komsebenzi we-thermogenic, akazange anciphise kwiqela lama-30 ° C. Ngapha koko, amanqanaba e-UCP1 kwiimpuku ezintathu ziphezulu kunakwiqela lama-22 ° C, kunye ne-vegf-a kunye ne-adrb2 bephakanyisiwe. Xa kuthelekiswa neqela le-22 ° C eligcinwe nge-25 ° C kwaye i-27.5 ° C ayibonisi (umzobo wokuxabangela 1).
- ubunzima bomzimba (a), ubunzima obuncindi (b) kunye nobunzima be-FAT (c) emva kweentsuku ezili-9 (ngosuku olunye ngaphambi kwenkqubo yeSob). D Ukusetyenziswa kwamandla (EE, KCAL / H). I-Endiction ephakathi kwamandla (0-96 iiyure) kubushushu obahlukeneyo (i-KCal / 24 iiyure). F I-F RANDRORTRATOTOTOTORORTRATOROTOROTOR TRATIO (URRE, VCO2 / VO2). g Ithetha i-rer (i-VCO2 / VO2). H itoti yokutya (g). Ndithetha ukutya okutyayo (G / iiyure ezingama-24). j Iyonke yokusetyenziswa kwamanzi (ml). k ophakathi ukusebenzisa amanzi (ml / 24 h). Inqanaba lomsebenzi owodwa (m). Inqanaba lomsebenzi (m / 24 h). n ubunzima bomzimba ngomhla wama-23 (g), o tshintsho kubunzima bomzimba, ubunzima be-P Lean, q Ukutshintsha kobusuku (g) Ngomhla we-23, g) nge-23 -dy, amanqatha Ubunzima (g) Xa kuthelekiswa nosuku 8, usuku 23 xa kuthelekiswa no -8. Ukubaluleka kwenkcukacha-manani kumanyathelo aphindaphindiweyo kwavavanywa kwe-One-Anova elandelwa luvavanyo lweTukey. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * ઇ than <0,05, *** р <0,001, **** р <0 ~ 0,0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * P <0.05, *** p <0.001, **** p <0.0001. * ઇ than <0,05, *** р <0,001, **** р <0 ~ 0,0001. * P <0.05, *** p <0.001, **** p <0.0001.Idatha inikezelwa njenge-Foble + Impazamo esemgangathweni yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe ziibhokisi ezingwevu. Amachaphaza kwi-fistograms abonisa iimpuku zomntu ngamnye. Ixabiso elibalulekileyo labalwa lonke ixesha lovavanyo (0-96 iiyure). n = 7.
Njengabantu, iimpuku zihlala zimisa i-micronveroninves ukunciphisa ilahleko yobushushu kwindalo esingqongileyo. Ukulinganisa ukubaluleka kwendalo esingqongileyo ye-EE nge-22, 25, 27.5, kunye ne-30 ° C, kunye nabalindi kunye nezixhobo zesikhumba. Nge-22 ° C, ukongezwa kwezikhuselo ezisemgangathweni kunciphisa i-EE malunga ne-4%. Ukudityaniswa okulandelayo kwezakhiwo zenzalo kunciphisa i-EE nge-3-4% (Fig. 5A, B). Akukho lutshintsho lubalulekileyo kwi-RER, ukutya ukutya, ukutya kwamanzi, okanye amanqanaba omsebenzi aqwalaselwa ngongezwa kwezindlu okanye izikhumba (umzobo 5i-p). Ukongezwa kolusu kunye nezinto zencanyuse kunye nokuncitshiswa kwe-EE nge-25 ne-30 c, kodwa iimpendulo zincinci kakhulu. Kwi-27,5 ° CA Umahluko waqwalaselwa. Ngokukodwa, kwezi zinto zixilongo, ihlile amanzi ubushushu obukhulayo, kule meko malunga ne-57% isezantsi kune-30 ° C (Fig-H). Uhlalutyo olufanayo lwenziwa kuphela kwinqanaba lokukhanya, apho i-EE yayikufuphi nenqanaba leMetal Metal Metal, kuba iimpuku ziphumle ikakhulu kulusu, iziphumo ze-2A-h) .
Idatha yeempuku ezivela kwiShelter kunye neZiseko zeNkulumbuso Ukusetyenziswa kwamandla (i-EE, i-KCAL / H) yamagumbi A, C, E kunye ne-22, 25,5 ukuya kwi-22. Idatha ye-IP yeempuku ibihlala nge-22 ° C: I-CRISIRARRATOROTOROTORRATOROTORY (RER, VCO2), i-VCO2), i-VCO2), i-GCE2), i-GARTACE YOKUGQIBELA (G), M Iyonke i-ITATE YAMANZI Idatha inikezelwa njenge-Foble + Impazamo esemgangathweni yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe ziibhokisi ezingwevu. Amachaphaza kwi-fistograms abonisa iimpuku zomntu ngamnye. Ukubaluleka kwenkcukacha-manani kumanyathelo aphindaphindiweyo kwavavanywa kwe-One-Anova elandelwa luvavanyo lweTukey. * P <0.05, ** p <0.01. * P <0.05, ** p <0.01. * Р <0,05, ** dayitha 0.01. * P <0.05, ** p <0.01. * P <0.05, ** p <0.01. * P <0.05, ** p <0.01. * Р <0,05, ** dayitha 0.01. * P <0.05, ** p <0.01.Amaxabiso aphakathi abalwa lonke ixesha lovavanyo (0-72). n = 7.
Kwimigangatho eqhelekileyo yobunzima (iiyure ezingama-2-3 zokuzila), ukukhulisa amaqondo obushushu ahlukeneyo akazange aphumelelise umahluko obonakalayo kwi-TG, 3-HB, i-cholesterol, i-AST, i-HDL njengomsebenzi wobushushu. Umzobo 6A-E). Ukuzingca ngokukhawuleza kwe-plasma, i-insulin, i-C-peptede, kunye neGlucagon khangehlukanise naphakathi kwamaqela (amanani 6G-J). Ngomhla wovavanyo lokunyamezelana kweglucose (emva kweentsuku ezingama-31 kubushushu obahlukeneyo), inqanaba le-Glucose yeGazi leGlucose (iiyure ezingama-5-6 zokuzila ukutya) kwakumalunga ne-6.5 mm, ngaphandle kwamaqela phakathi kwamaqela. Ulawulo lweglucose yomlomo yanda kakhulu kuwo onke amaqela, kodwa zombini uxinzelelo lwe-pice phantsi kwe-curves (iaucs) (i-IAUCS) (i-IAICS) (i-IAICS) (i-Iaucs) yayiphantsi kwi-30 ° C (P <0.05-p <0.0001, fig. I-6K, l xa kuthelekiswa neempuku ezigcinwe kwi-22, 25 ne-27,5 ° C (engahlukanga khona nganye nganye enye). Ulawulo lweglucose yomlomo yanda kakhulu kuwo onke amaqela, kodwa zombini uxinzelelo lwe-pice phantsi kwe-curves (iaucs) (i-IAUCS) (i-IAICS) (i-IAICS) (i-Iaucs) yayiphantsi kwi-30 ° C (P <0.05-p <0.0001, fig. 6k, l) xa kuthelekiswa neempuku ezigcinwe kwi-22, 25 ne-27,5 ° C (engahlukanga khona nganye nganye enye). Xhosa-Q Chate ,воюю знав,,,,,,,,,,,,,,,,,,,,,,, Нак аппп,, нак пиковавоя концентрцц и прия кь (Отдельнные временные точки: и <0,50-P <0,000 различчались межу соо соо соо соо соо соо соой Ulawulo lomlomo lweglucose lwanda kakhulu kwigazi lokugxininisa kuwo onke amaqela, kodwa zombini ukugxininiswa kwe-Peak kunye neNdawo yokunyusa phantsi kweQela le-30 ° le miz) P <0.0001, fig. 6k, l) xa kuthelekiswa neempuku zigcinwe kwi-22, 25 ne-27,5 ° C (engafaniyo).口服葡萄糖的给药显着增加了所有组的血糖浓度, 但在 30 饲养的小鼠组中 饲养的小鼠组中, 峰值浓度和曲线下增加面积 (iauc) (15-120 分钟) 均较低) 均较低 (各个时间点: P <0.05-p <0.0001, 图 6k, l) 与饲养在 22,25 和) 的小鼠.口服 口服 的 给 药 显着 了 的 的 浓度 饲养 饲养 饲养 饲养 饲养 饲养 饲养 饲养 中 中 中 增加 增加 增加 增加面积 面积 面积点 点: P <0.05-p < 0.0001, 图 6K, l) 与饲养在 22,25 和 I-27,25 和 ° 的小鼠.) 的小鼠.Ulawulo lomlomo lweglucose lwanda kakhulu kwi-Glucose yegazi kuwo onke amaqela, kodwa zombini uxinzelelo lwe-curve (iauc) (i-IAUC) (i-IAUC) (15-120 min) yayiphantsi kweqela le-30: P <0,05-p <0,0001, рс. : P <0.05-p <0.0001, fig.I-6l, l) Xa kuthelekiswa neempuku zigcinwe kwi-22, 25 ne-27,5 ° C (akukho mahluko omnye komnye).
Ukugxininiswa kwe-TRASMA ye-TG, i-3-HB, i-cholesterol, HDL, i-AST, i-FFOPINE, i-Intanethi, i-Intanethi, i-Clycen, i-Clycen, kunye ne-Glucagon, i-33 yeentsuku zokuFunda kubushushu obonisiweyo . Iimpuku azizange zindle iiyure ezingama-2-3 ngaphambi kokuba isampula yegazi. Olunye ukhetho lwaluvavanyo lokunyamezelana ngomlomo, olwenziwe kwiintsuku ezimbini ngaphambi kokuphela kwesifundo kwiimpuku ezizinzileyo kwiiyure ezingama-5-6 kwaye zigcinwe kubushushu obufanelekileyo iintsuku ezingama-31. Iimpuku zicelomngeni nge-2 g / kg ubunzima bomzimba. Indawo ephantsi kwedatha yejika (l) ibonakaliswa njengedatha yokunyusa (iauc). Idatha inikezelwa njenge-± ye-± ye-± ye-± ye-SEM. Amachaphaza amele iisampulu zomntu ngamnye. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,000, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,000, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7.
Kwi-DIO MICE (ikwazipho malunga neeyure ezingama-2-3), i-Plasma Cholesterol, HDL, Alt, i-AST, kunye neFFA ekugxilwe kuzo zahlukile phakathi kwamaqela. Zombini i-TG kunye ne-Glycerol ziphakanyisiwe kakhulu kwiqela lama-30 ° C xa kuthelekiswa neqela lama-22 ° C iqela (amanani 7a-h). Ngokwahlukileyo, i-3-GB yayimalunga ne-25% isezantsi kwi-30 ° C ngokuthelekiswa ne-22 ° C (umzobo 7b). Ke, nangona iimpuku zigcinwe kwi-22 ° C yayinelungelo lokuzinza elihle, njengoko kucetyiswa ukubaluleka kwe-TGE, i-Glycerol, i-Glycerol, i-3-HB xa isampulu yayingaphantsi kwe-22 ° C C. ° C. Iimpuku ziyakhuliswa kwi-30 ° C ngesayensi engabinayo. Ihambelana noku, ukugxininiswa kwesibindi kwe-Glycerol kunye ne-TG, kodwa hayi i-glycogen kunye ne-cholesterol kunye ne-cholesterol, yayiphezulu kwiqela lama-30 fugrament (D). Ukuphanda ukuba umahluko oxhomekeke kubushushu kwiLipolysis (njengoko kulinganiswa iplasma tg kunye ne-glycerol) sisiphumo sotshintsho lwangaphakathi kwivenkile ekupheleni kwesifundo kunye ne-Acid e-Acid yeFotty Acid e-Acid Vivo. ndikhulule i-glycerol. Kuwo onke amaqela ovavanyo, abacacisayo kwiisampulu zezicubu ezivela kwi-epididymy kunye ne-guinal Depots ibonise ukunyuka ezimbini kwi-Glycerol kunye ne-FFA-SEFREAT ekuphenduleni. Nangona kunjalo, akukho siphumo sobushushu be-Shell kwi-basial okanye i-Iyoprotenol-i-Lipolysis ifunyenwe. Iyahambelana nobunzima obuphezulu kunye nobunzima obukhulu, amanqanaba ePlasma Lepptin babe ngaphezulu kakhulu kwiqela lama-30 ° C kuneqela le-22 ° C). Ngokuchasene noko, amanqanaba ePlasma ye-Insulin kunye ne-C-pertide engafaniyo phakathi kwamaqela obushushu (kodwa k) i-Pllucagon ibonisa ukuxhomekeka kubushushu, kodwa kule meko ikwiqela elichasene ne-22 phantse kabini ngokuthelekiswa kabini ukuya kwi-30 ° C. Ukusuka. Iqela C (Fig. 7L). I-FGF21 ayifani phakathi kwamaqela ahlukeneyo amaqondo (i-7m). Ngomhla we-OGTTT, i-Glucose yegazi yayimalunga ne-10 mm kwaye ayifani phakathi kweempuku ezihlala kubushushu obahlukeneyo (Fig. 7N). Ulawulo lomlomo lweglucose lunyusa amanqanaba eglucose yegazi kwaye igcinwe kuwo onke amaqela kwi-18 mm 15 emva kodongwe. Kwakungekho umahluko kwi-IAUC (15-120 min) kunye nokugxininiswa kwamanqaku ohlukeneyo emva kwe-Dose (15, 60, 60, 90, 90 imiz) (o).
Ukugxininiswa kweplasma ye-TG, i-3-HB, i-cholesterol, HDL, i-AST, i-FFOID, i-Intanethi, i-CLFIN, i-CLF21 iboniswe kwiintsuku ezingama-33 zokuondla. Iqondo lokushisa elichaziweyo. Iimpuku azizange zindle iiyure ezingama-2-3 ngaphambi kokuba isampula yegazi. Uvavanyo lokunyamezelana ngomlomo lwalungaphandle njengoko lwenziwa kwidosi ye-2 g / kg ubunzima bomzimba weentsuku ezimbini ngaphambi kokuphela kwe-5-6 iiyure kwaye zigcinwe kwiqondo elifanelekileyo leentsuku ezingama-31. Indawo ephantsi kwedatha yejika (o) iboniswe njengedatha eyongezelelweyo (iauc). Idatha inikezelwa njenge-± ye-± ye-± ye-± ye-SEM. Amachaphaza amele iisampulu zomntu ngamnye. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,000, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7. * P <0,05, ** p <0,01, ** p <0,001, **** p <0,000, N = 7. * P <0.05, ** p <0.01, ** p <0.001, **** p <0.0001, N = 7.
Ukudluliselwa kwedatha ye-rodent ebantwini yimbandezelo entsonkothileyo ekutolikeni ukubaluleka kokuqwalaselwa kwimeko yophando lomzimba kunye nephamma. Ngenxa yezizathu zezoqoqosho kunye nokwenza lula uphando, iimpuku zihlala zigcinwa kubushushu begumbi ngaphantsi kwendawo yazo ye-thermonteratraltortor, ekhokelela ekusebenzeni kweenkqubo ezahlukeneyo zokulungisa izinto ze-metabos kunye nokungaphazamiseli ukuguqulwa kwemeta. Ke, ukuvezwa kweempuku kubandayo kunokubonelela ngemayile ekutyeni kakhulu kwaye kungathintela i-hyperglycemia kwi-rats ye-glucose ye-Glualin. Nangona kunjalo, akucacanga ukuba ukuvezwa kolawulo lweqondo lokuhlala ixesha elide (ukusuka kwigumbi ukuya kwi-thermoutral) ichaphazela i-thesostas eyodwa ye-godiostas) kunye ne-DFD) kunye ne-Ditabolic Parameter, kunye nenqanaba apho babekwazi ukulungelelanisa ukwanda kwe-EE ngolwando lokutya. Isifundo esinikezwe kweli nqaku sijolise ekuziseni ukucaciswa kwesi sihloko.
Sibonisa ukuba kwiimpuku eziqhelekileyo zobunzima kunye neempuku zedayi zedio, i-EE inxulumene neqondo lobushushu begumbi phakathi kwe-22 ne-30 ° C. Yiyo loo nto nge-EE nge-22 ° C yayimalunga ne-30% ephezulu kune-30 ° C. kuzo zombini iimodeli zemouse. Nangona kunjalo, umahluko obalulekileyo phakathi kweempuku eziqhelekileyo zeempuku kunye neempuku zedio yile ngelixa i-mice ye-gesi eqhelekileyo ehambelana neqondo lokutya ngokulungelelanisa ngokutya, ukutya kweempuku zahluka ngokwahlukeneyo. Amaqondo obushushu afundwayo ayefana. Emva kwenyanga enye, i-Dio Mice igcinwe kwi-30 ° C efumana ubunzima bomzimba kunye nobunzima obune-° C, c, ngelixa abantu abaqhelekileyo bengazange bakhokelele kumkhuhlane. Umahluko oxhomekekileyo kubunzima bomzimba. iimpuku zobunzima. Xa kuthelekiswa namaqondo obushushu kufutshane ne-thermonter okanye kubushushu begumbi, ukukhula kubushushu begumbi kubangele i-dio okanye inyama yegugu eziqhelekileyo kwi-diet ephezulu yokutya kodwa hayi kwisisindo esiqhelekileyo sokufumana ubunzima obuncinci. umzimba. Ixhaswanga zezinye izifundo17,18,19,20,21,21 kodwa ingeyiyo yonke22,23.
Ukukwazi ukwenza i-micronvevialvisive ukunciphisa ilahleko yobushushu yi-hypotheadwed yokutshintsha ukungathathi cala kwe-thermal ukuya ekhohlo ukuya kuthi ga kwi-EE kodwa engathathi cala i-C. Ngenxa yoko, idatha yethu ayixhasi into ephantsi kwe-thermonetralution kwiimpuku ezinamadolo enye, okanye ngaphandle kwezindlu ezityetyileyo okusingqongileyo, kufuneka zibe ngama-26 ukuya kwi-26 ukuya kwi-26 ° C njengoko kubonisiwe ezinye izifundo ezibonisa ubuchwephesha. Iqondo lobushushu lama-30 ° C kwi-mice ye-SICE7, 10, 24. Ukwenza ubunzima, indawo ye thermoralution kwimayile ibonakalisiwe kwiSigaba sokuPhumla (ukukhanya) Ukuveliswa ngenxa yomsebenzi kunye nokutya okubangelwa yi-thermogenesis. Ke, kwinqanaba lokukhanya, indawo esezantsi yokungathathi hlangothi iguqukele kwi-29 ° st, nakwinqanaba elimnyama, ~ ~ ~ ~25.
Ekugqibeleni, ubudlelwane obuphakathi kobushushu obunobushushu kunye nokusetyenziswa kwamandla ngokupheleleyo kugqitywe kukutya kobushushu. Kule meko, umyinge womphezulu kwivolumu sisimiselo esibalulekileyo semvakalelo ye-thermal, echaphazela zombini ukungavisisani kobushushu (indawo yomphezulu) kunye nomsindo (ivolumu). Ukongeza kwindawo engaphezulu, ukuhanjiswa kobushushu kukwagqitywa ngokufakwa (umyinge wokudluliselwa kobushushu). Ebantwini, ubunzima obutyebileyo bunokunciphisa ilahleko yobushushu ngokwenza isithintelo esirhabaxa esijikeleze iqokobhe lomzimba, kwaye kucetyisiwe ukuba ubunzima be-thermontels ibalulekile kwaye kuncitshiswe imvakalelo yobushushu i-therma ngokungangathathi hlangothi ( curve thando). Iqondo lokushishi elithelekiswa ne-EE) 12. Isifundo sethu bebengenziwanga ukuba sivavanye ngqo olu lwalamano lwamabala kuba idatha yokwenziwa komzimba iqokelelwe kwiintsuku ezili-9 ngaphambi kokuba idatha yenkcitho iqokelelwa kwaye ngenxa yokuba ubunzima benkcitho bekungazinzanga kwisifundo ngasinye. Nangona kunjalo, kuba ubunzima obuqhelekileyo kunye ne-dio mice inama-30% e-EE kwi-30 ° C kune-22 ° C ngaphandle kokungafani kwe-5 ° ukuya kwi-5 okanye idatha yethu ayixhasi ukuba ukukhumbula okukhulu kufuneka kunikezelwe ukufakelwa kakhulu. Inqaku, ubuncinci hayi kuluhlu lobushushu ophando. Oku kuhambelana nezinye izifundo kuze kube lula ukuphonononga le4,24. Kwezi zifundo, isiphumo sokukhubazeka sokukhuluphala sincinci, kodwa uboya wafunyanwa ukubonelela nge-30-50% yokufakelwa kwe-thermal ngokupheleleyo4,24. Nangona kunjalo, kwimayile efileyo, ukuqhutywa kwe-thermal kwandiswa malunga ne-450% ngokukhawuleza emva kokuba umntu efile, ephakamisa indlela ye-fursological, kubandakanya i-vasococliction, ukusebenza. Ukongeza kwimiyalelo yezinto eziphilayo kuboya phakathi kweempuku nabantu, imeko engekho mthethweni yokutyeba kakhulu kwiimpuku zinokuphenjelelwa ngenxa yezithambiso ezinamafutha omntu (ubungqingqwa) 26,27. Ngokwesiqhelo kwi-rodents ngaphantsi kwe-20% ye-Aultional STAT28. Ukongeza, inani lilonke lamafutha alinakuba ngumlinganiso we-suboptimal yokufakelwa komntu oshushu, njengoko ithe yaxolelwa ukuba ukuphunyezwa okuphuculweyo kukhuliswe yilahleko yendawo (kwaye ke yonyusa ukulahleka kobushushu) njengokunyuka kobushushu. .
Kwimilinganiselo yesiqhelo ye-round, yokuzila ngokukhawuleza kwe-TG, i-3-HB, i-Cholesterol, HDL, i-HDL, i-Alt, kunye ne-AST, i-AST, i-AST, i-MALS ikwimeko efanayo ye-5 yamandla. zazifana nobunzima kunye nobume bomzimba njengakuphela kwesifundo. Iyahambelana nokufana ngokufana kwi-DATAT, kwakungekho manqanaba ahlukeneyo kumanqanaba amaPlasma Leptin, okanye kwi-Insulin ekhawulezayo, i-C-Poptide, neGlucagon. Iimpawu ezingaphezulu zafunyanwa kwiimpuku zedio. Nangona iimpuku nge-22 ° C nazo azinawo amandla amabi apheleleyo kweli meko (njengoko zifumana ubunzima), ekupheleni kophononongo babenelungelo lokuthelekiswa namandla xa kuthelekiswa ne-30 ° C, kwiimeko ezinje I-Kights ephezulu. Ukuvelisa umzimba (3-GB) kunye nokwehla kwi-Glycerol kunye ne-TG kwiPlasma. Nangona kunjalo, umahluko oxhomekekileyo kubushushu kwiLipolysis ayibonakali ngathi yindawo yotshintsho lwe-epididymone, kuba i-FFAINAL, efana notshintsho kwifutha elikhutshwe kwezi meko Amaqela ayafana omnye komnye. Nangona singakhange siphande ngethoni yovelwano kuphononongo lwangoku, abanye bafumanise ukuba (ngokusekelwe kumgangatho wentliziyo kwaye kuthetha ukuba i-arrial fast) ihambelana nobushushu be-30 ° C kune-22 ° C C ngenxa yoko, umahluko oxhomekekileyo kubushushu ngethoni enovelwano ingadlala indima kwiLiphulissis kwisifundo sethu, kodwa ukunyuka kwethoni enovelwano kunokuvuselela ithoni, ezinye iindlela Inokuchasana nokuncipha kweempuku ezikhulisiweyo. Indima enokubakho yokuqhekeka kwamafutha omzimba. Ubushushu begumbi. Ngaphaya koko, inxalenye yefuthe elivuselelekileyo le-lipolysis ithethwe ngokungathanga ngqo kwi-inselin ye-insulin, kodwa kwisifundo se-Infoulin kunye ne-C-Peptude enovelwano ngamaqondo obushushu ahlukeneyo akwanelanga ukutshintsha i-lipolysis. Endaweni yoko, safumanisa ukuba umahluko kwimo yamandla yayisengozini enkulu kulo mahluko kwiimpuku. Izizathu ezisisiseko ezikhokelela kulawulo olungcono lokutya nge-EE kwi-EE kwi-vice eqhelekileyo ifuna ukuqhubeka nophando. Ngokubanzi, nangona kunjalo, ukutya ukutya kulawulwa yi-cuestatic kunye ne-hedonic cies31,32,33. Nangona kukho ingxoxo malunga nokuba yeyiphi kwezi zibonakaliso ezimbini zibaluleke ngakumbi, ezingama-31,32,33 eyaziwa ukuba ukusetyenziswa kwexesha elide lokutya okuphezulu kukhulisa i-homeostassis. . -Ukutya ukutya okutyayo34,35,36. Ke ngoko, i-Hodonic yondla kwi-Dio Muce ithwaxwa nge-45% ye-HFD inokuba sesinye sezizathu zokuba le misi ingalungelelanga ukutya nge-EE. Okubangela umdla kukuba, umahluko ekuthatheni kunye negazi le-Glucose-elawula iihomoni ezigcinwe kwi-dice yeqondo leqondo lobushushu, kodwa hayi kwiimpuku eziqhelekileyo. Kwi-DIO MICE, amanqanaba e-Plasma Lepptin anyuke ngamaqondo obushushu kunye namanqanaba eGlucagon anciphe ngamaqondo obushushu. Ubungakanani beqondo lobushushu elinokuthi lichaphazele ngokuthe ngqo ukufunda, kodwa kwimeko ye-leptin, ibhalansi engalunganga yamandla kwaye ke i-FORD AMANZI AMAZWE KWI-MAGINE KWI-MAGINE KWI-MAGINE NEPHING NEPTIIN SUPTIn Ukunxibelelana kakhulu37. Nangona kunjalo, ukutolikwa komqondiso weGlucagon kuyadideka ngakumbi. Njenge-Insulin, ukhuseleko lwe-glucagon lwalunyuswa kakhulu yithoni enovelwano, kodwa oyena mntu uphakamileyo welizwi waxelwa kwangaphambili ukuba kwiqela le-22 ° CADE, elinengxaki yePlasma Glucagagon. I-Insulin yenye uMlawuli oQinisekisiweyo wePlasma Glucagon, kunye nokunganyangeki kwe-insulin kunye ne-Diabetes ezi-2 ezinxulunyaniswa kakhulu nokuzila ngokukhawuleza kunye ne-Phyperglucaguaguaguagonemia 38,39. Nangona kunjalo, iimpuku zedio ekufundeni kwethu zazingakhathali, ke oku akunakuba yinto ephambili ekunyukeni kwiqela le-Glucagon kwiqela le-22 ° C Iqela leqela le-22. Umxholo wamafutha we-Lillr unxulunyaniswa nokwanda kwe-Plasma Glucagon Constical, iindlela zazo, zinokujikeleza kwe-hepatic gesions, kunye nokunyuka kwe-Amino Acid Cereutot 42. Nangona kunjalo, ukulungiselela ukugxininiswa kwe-glycerol kunye ne-TG ayifani phakathi kwamaqela obushushu kwisifundo sethu, oku akunakuba yinto enokubakho ekwandeni kwe-PLASMA kwiqela le-22 ° C. I-Triodioidyfolline (T3) idlala indima ebalulekileyo kwi-metabolicres iyonke kunye nokuqaliswa kweMetabolic kwi-hypothermia43,44. Ngenxa yoko, uxinzelelo lwePlasma T3, ekunokwenzeka ukuba lulawulwa ziindlela eziphakathi, ezingama-45,46 zonyuka kuzo zombini iimpuku nabantu abangaphantsi kweemeko ze-thermonter47, nangona ukwanda kwabantu kuncinci, nto leyo ichazwe kakhulu kwiimpuku. Oku kuyahambelana nokulahleka kobushushu kwindalo esingqongileyo. Besingalingani iPlasma T3 Ukugxininiswa kwesifundo sangoku, kodwa ukugxininisa kusenokwenzeka ukuba babesezantsi kwiqela lama-30 ° C, elinokucacisa iziphumo zeli qela kumanqanaba ePlasma Glucagon, njengoko (ezinye ziyibonisile loo nto I-T3 yonyusa i-plasma glucagon ngendlela exhomekeke kwidosi. Iihomoni ze-Hidroid zixeliwe ukuba zikhuphe intetho ye-FGF21 kwisibindi. NjengeGlucagon, ugxininiso lwePlasma Fgf21 lunyuke nge-plasma t3 ukugxininisa (i-GGFEAT Fig. 48), kodwa kuthelekiswa neGlucagon, i-FGF21 i-PLASMA kwisifundo sethu ayichaphazelekanga. Izizathu ezisisiseko zokungangqinelani zifuna ukufundisisa, kodwa i-T3-i-T3-i-T3 ye-FGF21 ifanele yenzeke kumanqanaba aphezulu e-T3 eqhutywa kwi-T3-i-Glucagon Glucagon Glucagon ye-T3. 5b).
I-HFD ibonisiwe ukuba inxulunyaniswa kakhulu nokunganyangeki kwe-glucose ye-glucose kunye nokunganyangeki kwe-Insulin (iMakishi) kwi-MICO i-22 ° C. Nangona kunjalo, i-HFD yayinganxulunyaniswa nokuba unganyamezeli i-glucose okanye ukunganyangeki kwe-isulin xa ikhule kwindawo ye-thermotlelt (echazwe apha i-28 ° C) 19. Kwisifundo sethu, olu lwalamano aluzange luphindwe kwiimpuku zedio, kodwa iimpuku eziqhelekileyo eziqhelekileyo ezigcinwe kwi-30 ° C iphumelele ukunyamezelana kweglucose. Isizathu soku lo mahluko sifuna ukuqhubeka nesifundo, kodwa sinokuphenjelelwa sisibakala sokuba i-DIO yeempuku zam kwisifundo se-inseulin, ngokungxama kwe-Callin C-peptide i-Informade ye-12 ukuya kwi-20 amaxesha aphezulu kunemigangatho yesiqhelo. nasegazini kwisisu esingenanto. Ukugxininiswa kwe-glucose malunga ne-10 mm (malunga ne-6 mm kubunzima bomzimba obuqhelekileyo), oko kubonakala ngathi kushiya iwindow encinci kuyo nayiphi na imiphumo yolwazi yokuphucula ukunyamezelwa kwe-thertoose. Into edidayo kukuba, ngenxa yezizathu ezisebenzayo, i-OGTT yenziwe kubushushu begumbi. Ke, iimpuku zihlala kumaqondo obushushu aphezulu awazisileyo othukayo othusayo, onokuthi achaphazele ukufunxa / ukucaciswa. Nangona kunjalo, ngokusekwe kwi-Glucose efanayo yegazi kumaqela ahlukeneyo amaqondo obushushu, iinguqu kubushushu be-amolgesent azinakuchaphazela kakhulu iziphumo.
Njengoko bekutshiwo ngaphambili, kutshanje iqaphelwe ukuba ukwandisa amaqondo obushushu kwigumbi kunokuthathelela ingqalelo ethile kuxinzelelo olubandayo, olunokutsalela umnxeba kwi-Transfeed to of datch yedatha. Nangona kunjalo, akucaci ukuba yintoni iqondo lobushushu elifanelekileyo lokugcina iimpuku ukuba zilime ngomzimba. Impendulo yalo mbuzo inokuphenjelelwa yintsimi yesifundo kunye nesiphelo sokufunda. Umzekelo woku sisiphumo sokutya kwi-Livel Fight, i-Glucose Golloses kunye ne-Insulin19. Ngokwenkcitho yenkcitho, abanye abaphandi bakholelwa ukuba ubushushu be-thermoutral liyiqondo elingakumbi lokukhulisa, kwaye abantu bafuna ukuba amaqondo obushushu omzimba aphambili, kwaye bachaza amaqondo obune amathaphu ama-30 ° C7,10. Abanye abaphandi bakholelwa ukuba iqondo lobushushu liyakholelwa ukuba abantu baqhelene neempuku zabantu abadala kwidolo elinye lingama-23 ukuya kwe-22 ° C, njengoko babefumana i-26 ° C kwaye ngokusekelwe kubantu abaphantsi kwe-3 ° C. Ubushushu babo obuncinci obukhulu, oluchazwe apha ngama-23 ° C, buyi-8.12. Isifundo sethu sihambelana nezinye izifundo ze-therm azifikanga kwi-26-28 ° 7, 10, 11, 25, ibonisa ukuba iphantsi kakhulu. Enye into ebalulekileyo ekufuneka uyiqwalasele malunga nobushushu begumbi kunye ne-thermonetralution kwi-muce okanye izindlu zeqela. Xa iimpuku zihlanjululwe ngokwamaqela kunezifundo zethu, njengakwisifundo sethu, ubushushu bancitshiswa, kungenzeka ukuba baninzi kwezilwanyana. Nangona kunjalo, ubushushu begumbi yayisezantsi kwe-LTL ye-25 xa kwasetyenziswa amaqela amathathu. Mhlawumbi ezona zinto zibaluleke kakhulu ngokuchasene noku kukubaluleke kakhulu komsebenzi webat njengezikhusela kwi-hypothermia. Ngenxa yoko, ngelixa iimpuku zibuyekezwa kakhulu kwi-calori yabo ephezulu yokuphulukana nomsebenzi we-BAT, ongaphezulu kwe-60% ye-5 yedwa, i-51 52 igalelo lomsebenzi we-BALD kwi-EE wawuphakamile, omncinci kakhulu. Ke ngoko, ukunciphisa umsebenzi wabatwa kunokuba yinto ebalulekileyo yokwandisa inguqulelo yabantu. The regulation of BAT activity is complex but is often mediated by the combined effects of adrenergic stimulation, thyroid hormones and UCP114,54,55,56,57 expression. Idatha yethu ibonisa ukuba iqondo lobushushu kufuneka likhuliswe ngaphezulu kwe-27,5 ° le-C ngokuthelekiswa neempuku nge-22 ° C ukuze ifumanise umahluko kwimbonakalo ye-BAT inoxanduva lomsebenzi / olwenziweyo. Nangona kunjalo, umahluko ofunyenwe phakathi kwamaqela angama-30 nama-22 e-C engasoloko ebonisa ukwanda komsebenzi we-BIT kwi-22 ° Cela i-CAG1, i-ADRB2 kunye neVegf-A yakhutshwa kwiqela lama-22 ° Ingcambu yezi ziphumo zingalindelekanga ihleli zimiselwe. Inokwenzeka into yokuba intetho yabo ayizukubonisa umqondiso wegumbi eliphakamileyo, kodwa endaweni yoko lenza ukuba isuka kwi-30 ° C ukuya kwi-22 ° 6 . ).
Umqobo ngokubanzi wesifundo sethu kukuba sifunde kuphela iimpuku ezingamadoda. Olunye uphando lubonisa ukuba isini sinokuba luqwalaselo olubalulekileyo kwiimpawu zethu eziphambili, njengoko iimpuku ze-gue-tice ezingamadolo zinobuthathaka kakhulu ngenxa yokuqhutywa kobushushu obuphezulu kunye nokugcina ubushushu obukhulu obungalawulekiyo. Ukongeza, iimpuku zabasetyhini (kwi-HFD) ibonise umanyano olukhulu lwamandla kunye ne-EE kwi-30 ° C ngokuthe xa kuthelekiswa neempuku ezingamadoda ezityiweyo zesondo ezifanayo (20 ° C kule meko) 20. Ngenxa yoko, kwiimpuku zabasetyhini, ifuthe le-ficritheralwazic umxholo uphakame, kodwa inepatheni efanayo nakwiimpuku ezingamadoda. Kwisifundo sethu, sigxile kwiimpuku ezingamadoda amane, njengoko ezi ziimeko apho uninzi lwezifundo ze-metabolic ezivavanywa i-EE ziqhutywa. Omnye umda wesifundo sethu kukuba iimpuku zazikukutya okufanayo kuzo zonke isifundo, esathintela ukufundela ukubaluleka kwegumbi lokuguquguquka kwe-metabolic kwiingoma ezahlukeneyo ze-Macronroutrieries. Kwii-mnigy kunye neempuku zamadoda zigcinwe nge-20 ° C xa kuthelekiswa neempuku ezihambelana ne-30 ° C.
Ukuqukumbela, isifundo sethu sibonisa ukuba, njengabanye bezifundo, iimpuku ezi-1 eziqhelekileyo ze-thermoflotralt ngaphezulu kwe-27,5 ° C. Ukongeza, ukufundisisa kwethu kubonisa ukuba ukutyeba kakhulu ayisiyonto iphambili kwiimpuku ezinobunzima obuqhelekileyo okanye i-dio, kukhokelela kubushushu obufanayo: i-EE Rices kwi-dio kunye neempuku eziqhelekileyo. Ngelixa ukutya okunemigangatho eqhelekileyo yobunzima bekungqinelana ne-EE kwaye ke kugcinwe ubunzima bomzimba obuzinzileyo kuluhlu lonke lobushushu, ukutya kweempuku zakwe-dio kwakufana nomlinganiso ophezulu weempuku ezingama-30 ° C . Nge-22 ° C efumana ubunzima bomzimba. Ngokubanzi, inkqubela phambili ecwangcisiweyo yokuvavanya ukubaluleka kokuphila ngezantsi kwamaqondo obushushu e-thermonteral afunwa kubangela ukuqaqadeka okungalunganga phakathi kwegundane kunye nezifundo zomntu. Umzekelo, kwizifundo ezikhulayo, inqaku eliyinxenye lokuguqulwa okungalunganga kunokubangelwa yinto yokuba izifundo ze-MURINE zoMlinganiso zihlala zisebenza kwizilwanyana ezinobushushu obunexabiso elifanelekileyo. Ukulahleka kwesisindo xa kuthelekiswa nobunzima bomzimba olindelekileyo, ngakumbi ukuba indlela yentshukumo ixhomekeke kwi-EE ngokwandisa umsebenzi we-BIP, osebenza ngakumbi kwaye usebenze kubushushu begumbi ngaphezulu kwe-30 ° C.
Ngokungqinelana noMthetho woPhingo lweSilwanyana saseDanish (1987) kunye namaziko ezempilo kazwelonke (upapasho Nomb. 85-23) kunye neNgqungquthela yaseYurophu esetyenziselwa ukuvavanywa kunye nezinye iinjongo zenzululwazi (iBhunga lezesayensi (iBhunga laseYurophu. 123, Strasbourg , 1985).
Ishumi lamashumi amabini anesihlanu elineeveki ze-C57bl / 6j mice ifunyenwe kwi-Janvier Saint Berthevin ceseever, iFrance 1324) kunye ne-Ad-Adlin 1324) kunye ne-Ad-Adline 1324 ubushushu begumbi. Iimpuku zedio ze-dio (iiveki ezingama-20) zafunyanwa kumthengisi ofanayo kwaye zanikwa ukufikelela kwi-45% yokufikelela kwi-45% yokutya okuphezulu kwamafutha (ikati. Hayi. I-NJ, i-USA) kunye namanzi aphantsi kwemeko yokukhulisa. Iimpuku zazilungelelaniswa okusingqongileyo ngeveki ngaphambi kokuqala kwesifundo. Iintsuku ezimbini ngaphambi kokutshintshelwa kwinkqubo ye-carifatry engathanga ngqo, iimpuku zaqengqeleka, ziphantsi kwe-MRI (i-Echomrim, i-Echomrim, i-Echomrim, i-USA, i-USA) yahlulahlulwe ngokwamaqela amane ahambelana nobunzima bomzimba, ubunzima obuqhelekileyo.
Umzobo wegrafu wendlela yokufunda ubonisiwe kwi-8. Iimpuku zatshintshelwa kwi-carimet ye-carimet evaliweyo kunye neqondo elingalinganiyo elilawulwa ngeqondo le-seble kwi-indals Amanqanaba omsebenzi ngokulinganisa i-Beam iqhekeza. I-XYZ. Iimpuku (n = 8) zazigcinwe ngo-22, 25,5, okanye i-30 ° C esebenzisa i-Bedring kodwa ikhusi kunye nendawo enobumnyama (ukukhanya: 06: 00) . I-2500ml / min. Iimpuku zaziqhutywa ngeentsuku ezisi-7 ngaphambi kobhaliso. Ukurekhodwa kwaqokelelwa iintsuku ezine ngokulandelelana. Emva koko, iimpuku zigcinwa kubushushu obunama-25, 27,5, kunye ne-30 ° C kwiintsuku ezili-12 ezongezelelekileyo, emva koko kongezwa iseli njengoko kuchaziwe ngezantsi. Okwangoku, amaqela eempuku agcinwe nge-22 ° C egcinwe kweli thuba ezimbini iintsuku (ukuqokelela idatha entsha), kwaye emva koko iqondo lobushushu lalonyuswa ngamanqanaba e-2 ° C ngalo lonke ixesha ekuqaleni kwesigaba sokukhanya ( Ngo-06: 00) kude kufike i-30 ° C emva koko, iqondo lobushushu lahliselwa kwi-22 ° C kunye nedatha eqokelelweyo enye iintsuku ezimbini. Emva kweentsuku ezimbini ezongezelelekileyo zokurekhoda nge-22 ° C, izikhumba zongezwa kuzo zonke iiseli kulo lonke ubushushu, kunye nokuqokelelwa kwedatha kwaqala ngomhla wesibini (usuku 17) kwaye iintsuku ezintathu. Emva koko (usuku lwe-20), ukongezwa kwezinto (8-10 g) kongezwa kuzo zonke iiseli ekuqaleni komjikelo wokukhanya (06: 00) kunye nedatha beqokelelwa kwenye iintsuku ezintathu. Ngenxa yoko, ekupheleni kwesifundo, iimpuku zigcinwe nge-22 ° C zigcinwe kweli gumbi ngeentsuku ezingama-21/33 kwaye nge-8 ° C kwiintsuku ezisi-8 ezidlulileyo, ngelixa iimpuku ngamanye ama-33 zigcinwe kweli nani i-33. / Iintsuku ezingama-33. Iimpuku zazondliwe ngexesha lokufunda.
Ubunzima obuqhelekileyo kunye neempuku zedio zilandele iinkqubo ezifanayo zokufunda. Emini -9, iimpuku zanyibilika, i-MRI ikhathazwe, yahlulahlulwe yangamaqela anokuthelekiswa nobunzima bomzimba kunye nokwenziwa komzimba. Ngosuku -7, iimpuku zatshintshelwa kwi-carimet ye-carect ye-carect ye-carering yenziwa yiNkqubo yeSolob (Nevada, eUSA). Iimpukane zazigcinwe ngokukodwa nge-bedding kodwa ngaphandle kwendlwana okanye izixhobo zokhuseleko. Iqondo lokushisa lisetwe ku-22, 25, 27.5 okanye i-30 ° C. Emva kweveki enye yokuvunywa (iintsuku -7 ukuya kwi-0, izilwanyana aziphazanyiswa), idatha iqokelelwe kwiintsuku ezine ngokulandelelana (iintsuku ze-4, 2, 5). Emva koko, iimpukane zigcinwe nge-25, 27,5 ne-30 ° C zigcinwe phantsi kweemeko ezingapheliyo de kube yimini ye-17. Kwangelo xesha, iqondo lobushushu kwiqela lama-22 ° C lanyuswa le-2 ° C imihla ngemihla ngokuhlengahlengiswa komjikelo wobushushu (06: 00 h) ekuqaleni kokuvezwa kokukhanya (idatha iboniswe kwi-Fig. 1) . Ngosuku lwe-15, amaqondo obushushu ahlise ukuya kwi-22 ° C kwaye iintsuku ezimbini zedatha eziqokelelweyo ukubonelela ngedatha yesiseko kunyango olulandelayo. Izikhumba zongezwa kuzo zonke iimpuku ngosuku lwe-17, kunye nezinto ezibonakalayo zongezwa ngomhla wama-20 (umzobo 5). Ngomhla wama-23, iimpuku zixinelelwa kwaye ziphantsi kwe-MRI, emva koko zashiywa zodwa iiyure ezingama-24. Ngosuku lwe-24, iimpuku zaziqiniswe ukusuka ekuqaleni kwefotoperper (06:00) kwaye ifumene i-OGTT (2 g / kg) ngo-12: 00 iiyure zokuzila ukutya). Emva koko, iimpuku zabuyiselwa kwiimeko zabo zokuzibopha kwaye zikhuliswe ngosuku lwesibini (usuku 25).
I-Dio Mice (n = 8) ilandele iprotocol efanayo njengeempuku eziqhelekileyo (njengoko kuchaziwe apha ngasentla nangomfanekiso 8). Iimpuku zigcina i-45% hfd kuzo zonke iindlela zokuvavanywa kwenkcitho yamandla.
I-VO2 kunye ne-VCO2, kunye noxinzelelo lwe-vapor yamanzi, zarekhodwa kwi-1 hz ngexesha leseli rhoqo kwi-2 min. Ukutya kunye nokutya kwamanzi kwaqokelelwa ngokurekhoda okuqhubekayo (1 hz) yobunzima bokutya kunye neendlela zamanzi. Ukubek'esweni okusemgangathweni kusetyenziswa ingxelo yesisombululo se-0.002 g. Amanqanaba omsebenzi arekhodwa kusetyenziswa i-3D xyz beam ye-xoy, idatha iqokelelwa kwisigqibo sangaphakathi se-240 HZ kwaye inikwe ingxelo nganye yesibini ukuba ithathe i-0,25 cm. Idatha yalungiswa ngenkqubo ye-SACRO ITATATATATATATITTATITTATITATITTATITATITATITARITT. Itoliki ye-MACRO ilungiselelwe ukuba ikhuphe idatha yemveliso yazo zonke iiparameter qho kwimizuzu emihlanu.
Ukongeza ekumiselweni kwe-EE, amaqondo obushushu anokulawula neminye imiba yeMetabolism, kubandakanya i-Potacose ye-Glucose ye-Glucose, ngokulawula imvimbo ye-glucose-metaboling yehomoni. Ukuvavanya le ngxaki, ekugqibeleni sawugqiba ukufundwa kobushushu bomzimba ngokuphosa iimpuku eziqhelekileyo ezinomthwalo we-daio ye-dio yomlomo (2 g / kg). Iindlela zichazwe ngokweenkcukacha ngezinto ezongezelelweyo.
Ekupheleni kwesifundo (usuku 25), iimpuku zazizila iiyure eziyi-2-3 (ukuqala ngo-06: 00), i-anesthetised e-Isforline, kwaye iqhutywa ngokupheleleyo ngokuthintela i-retoorbitata. Ukuxaniswa kwe-plasma lipids kunye nehomoni kunye nee-lipids kwiSibindi zichazwe kwizixhobo ezongezelelweyo.
Ukuphanda ukuba iqondo lobushushu le-soll libangela utshintsho olwenziweyo kwi-tishu yesicubu esichaphazela i-lipolysis, i-IngiInel kunye ne-epididyymil i-ted i-tishu ye-tishu yenziwa ngokuthe ngqo kwiimpuku emva kwenqanaba lokugqibela. Izicubu zenziwa zisebenzisa i-vivo ye-lipolysis esandula ukwenziwa echazwe kwiindlela ezongezelelweyo.
Izicubu ze-quissip ezi-brown (bat) ziqokelelwa ngomhla wokuphela kwesifundo kwaye zigqitywe njengoko kuchaziwe kwiindlela zokuxabangela.
Idatha inikezelwa njenge-± ye-± ye-± ye-± ye-SEM. Iigrafu zenziwa kwi-prograph ye-9 (i-LA JOLLA, i-CA) kunye nemizobo yahlelwa kwi-Adobe Mpheline. Intsingiselo yeenkcukacha-manani yavavanywa kwi-prographid prism kwaye ivavanywe ngovavanyo lwe-T-ndlela / iindlela eziphindaphindwe kabini / ezimbini zendlela elandelwa yi-TUTKEY YINGCICONOONOONOOONOOONS, okanye i-anova engafakwanga ikwavavanywa ngokuthelekisa okuninzi kweTuokey njengoko kufuneka. Ukusasazwa kwedatha ye-gausius yedatha iqinisekisiwe yi-D'adstino-Pearson Pearson ngaphambi kovavanyo. Ubungakanani besampulu buboniswa kwicandelo elihambelanayo lecandelo "Iziphumo", kunye nakwibali. Ukuphindaphinda kuchazwa njengawo nawuphi na umlinganiso othathwe kwisilwanyana esinye (kwi-vivo okanye isampulu ye-tishu). Ngokuphathelele ukubuyiswa kwedatha, ukunxulumana phakathi kwenkcitho yamandla kunye neqondo lobushushu kuboniswe kwizifundo ezine ezizimeleyo kusetyenziswa iimpuku ezahlukeneyo ngoyilo olufanayo lokufunda.
Iiprothokholi ezineenkcukacha zovavanyo, izixhobo, kunye nedatha eluhlaza iyafumaneka kwisicelo esivakalayo kwi-Coul Groe Grue E. Kuhre. Olu phononongo aluzange luvelise ii-regepnts ezintsha ezizodwa, izilwanyana ze-transgenic / zeseli, okanye ukulandelela idatha.
Ngolwazi oluthe kratya malunga noyilo lokufunda, jonga ingxelo yophando yendalo ngaphandle kwenqaku.
Yonke idatha yefom igrafu. I-1-7 ifakwe kwindawo yogcino lwedatha yesayensi, inombolo yofikelelo: 1253.11.sciedb.02284 okanye https: //oi.org/0.5760.02284. Idatha eboniswe kwi-EM inokuthunyelwa ukuba i-ruge e kuhre emva kovavanyo olusengqiqweni.
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Ixesha lokuposa: I-Oct-28 ukuya ku-2822
