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Uninzi lwezifundo zemetabolism kwiimpuku zenziwa kubushushu begumbi, nangona phantsi kwezi meko, ngokungafaniyo nabantu, iimpuku zichitha amandla amaninzi zigcina ubushushu bangaphakathi.Apha, sichaza ubunzima obuqhelekileyo kunye nokukhuluphala okubangelwa kukutya (DIO) kwi-C57BL / 6J iigundane ezityiswa i-chow chow okanye i-45% yokutya okunamafutha aphezulu, ngokulandelanayo.Iigundane zibekwe kwiintsuku ze-33 kwi-22, i-25, i-27.5 kunye ne-30 ° C. kwinkqubo ye-calorimetry engathanga ngqo.Sibonisa ukuba inkcitho yamandla inyuka ngokulandelelana ukusuka kwi-30 ° C ukuya kwi-22 ° C kwaye imalunga ne-30% ephezulu kwi-22 ° C kuzo zombini iimodeli zegundane.Kwiimpuku ezinobunzima obuqhelekileyo, ukuthathwa kokutya kuchasene ne-EE.Ngakolunye uhlangothi, iigundane ze-DIO azizange zinciphise ukutya xa i-EE yehla.Ngaloo ndlela, ekupheleni kophando, iigundane kwi-30 ° C zinesisindo somzimba esiphezulu, ubunzima be-fat mass kunye ne-plasma glycerol kunye ne-triglycerides kuneegundane kwi-22 ° C.Ukungalingani kwiimpuku ze-DIO kusenokuba kungenxa yokonyuka kokutya okusekwe kulonwabo.
Impuku yeyona modeli yezilwanyana isetyenziswa kakhulu kuphononongo lwefiziyoloji yabantu kunye ne-pathophysiology, kwaye ihlala isilwanyana esingagqibekanga esisetyenziswa kumanqanaba okuqala okufunyanwa kweziyobisi kunye nophuhliso.Nangona kunjalo, iimpuku zahlukile ebantwini ngeendlela ezininzi ezibalulekileyo zomzimba, kwaye ngelixa ukukala kwe-allometric kunokusetyenziswa kwinqanaba elithile ukuguqulela ebantwini, umahluko omkhulu phakathi kweempuku kunye nabantu ulele kwi-thermoregulation kunye ne-homeostasis yamandla.Oku kubonisa ukungangqinelani okusisiseko.I-avareji yobunzima bomzimba weempuku ezikhulileyo ubuncinane ngamaxesha aliwaka ngaphantsi kweyabantu abadala (i-50 g vs. 50 kg), kwaye indawo engaphezulu kumlinganiselo wobunzima iyahluka malunga namaxesha angama-400 ngenxa yenguqu yejometri engekho mgca echazwe nguMee. .I-Equation 2. Ngenxa yoko, iimpuku zilahlekelwa ubushushu obungakumbi ngokumalunga nomthamo wazo, ngoko ke zinovelwano ngakumbi kwiqondo lobushushu, zityekele ngakumbi kwi-hypothermia, kwaye zinezinga eliphakathi kwe-basal metabolic ngokuphindwe kashumi ngaphezulu kwelabantu.Kwiqondo lokushisa eliqhelekileyo legumbi (~22 ° C), iimpuku kufuneka zonyuse inkcitho yazo yonke yamandla (EE) malunga ne-30% ukugcina ubushushu bomzimba obungundoqo.Kumaqondo obushushu asezantsi, iEE yonyuka ngakumbi malunga ne-50% kunye ne-100% kwi-15 kunye ne-7°C xa kuthelekiswa ne-EE kuma-22°C.Ke, iimeko zezindlu ezisemgangathweni zibangela impendulo yoxinzelelo olubandayo, olunokuthi lubeke esichengeni ukuhanjiswa kweziphumo zempuku ebantwini, njengoko abantu abahlala kuluntu lwanamhlanje bachitha ixesha labo elininzi kwiimeko ze-thermoneutral (kuba indawo yethu ephantsi yomgangatho wemitha ukuya kwivolumu isenza singabi namvakalelo ubushushu, njengoko sidala indawo ye-thermoneutral (TNZ) ejikeleze i-EE ngaphezu kwe-basal metabolic rate) idibanisa ~ 19 ukuya kwi-30 ° C6, ngelixa iigundane zinebhendi ephezulu kunye nencinci ehamba nge-2-4 ° C7,8 Enyanisweni, oku kubalulekile. inkalo ifumene ingqwalaselo enkulu kwiminyaka yakutshanje4, 7,8,9,10,11,12 kwaye kuye kwacetyiswa ukuba ezinye “iintlobo ezahlukeneyo” zinokuncitshiswa ngokunyusa iqondo lobushushu leqokobhe 9. Nangona kunjalo, akukho mvumelwano kuluhlu lobushushu oko kwenza i-thermoneutrality kwiimpuku.Ngaloo ndlela, ingaba iqondo lokushisa eliphantsi eliphantsi kwinqanaba le-thermoneutral kwiigundane zedolo elilodwa lisondele kwi-25 ° C okanye lisondele kwi-30 ° C4, 7, 8, 10, 12 lihlala liphikisana.I-EE kunye nezinye iiparamitha zemetabolism zimiselwe iiyure ukuya kwiintsuku, ngoko ke umgama wokuba sesichengeni ixesha elide kumaqondo obushushu ahlukeneyo kunokuchaphazela imilinganiselo yemetabolism efana nobunzima bomzimba ayicacanga.ukusetyenziswa, ukusetyenziswa kwe-substrate, ukunyamezela kwe-glucose, kunye ne-plasma lipid kunye ne-glucose concentrations kunye namahomoni okulawula ukutya.Ukongeza, uphando olongezelelweyo luyafuneka ukuqinisekisa ukuba ukutya kunokuphembelela kangakanani ezi parameters (iimpuku ze-DIO kukutya okunamafutha aphezulu zinokujoliswa ngakumbi kukutya okusekelwe kulonwabo (hedonic)).Ukubonelela ngolwazi oluthe kratya kwesi sihloko, siye savavanya isiphumo sokukhuliswa kobushushu kwiiparamitha zemetabolism ezikhankanywe ngasentla kubunzima obuqhelekileyo beempuku zamadoda kunye ne-Diet-induced obese (DIO) yeempuku eziyindoda kwi-45% yokutya okunamafutha aphezulu.Iigundane zazigcinwe kwi-22, 25, 27.5, okanye i-30 ° C ubuncinane kwiiveki ezintathu.Amaqondo obushushu angaphantsi kwe-22°C awakaphononongwa kuba indawo yokuhlala yezilwanyana ayifane ibe ngaphantsi kweqondo lobushushu begumbi.Sifumene ukuba iigundane ze-DIO eziqhelekileyo-ubunzima obuqhelekileyo kunye nesangqa esinye ziphendule ngokufanayo kwiinguqu kwiqondo lokushisa elivaliweyo ngokwe-EE kwaye kungakhathaliseki ukuba imeko yokuvalwa (kunye okanye ngaphandle kwendawo yokuhlala / i-nesting material).Nangona kunjalo, ngelixa iigundane ezinobunzima obuqhelekileyo zilungelelanisa ukutya kwazo ngokwe-EE, ukutya kweempuku ze-DIO kwakungaxhomekekanga kwi-EE, okukhokelela ekubeni iigundane zithole ubunzima obuninzi.Ngokweenkcukacha zobunzima bomzimba, i-plasma concentrations ye-lipids kunye nemizimba ye-ketone ibonise ukuba iigundane ze-DIO kwi-30 ° C zine-balance balance yamandla ngaphezu kweegundane kwi-22 ° C.Izizathu ezisisiseko zomahluko kwibhalansi yokuthatha amandla kunye ne-EE phakathi kobunzima obuqhelekileyo kunye neempuku ze-DIO zifuna uphononongo olongezelelweyo, kodwa zinokunxulumana notshintsho lwe-pathophysiological kwiimpuku ze-DIO kunye nesiphumo sokutya okusekelwe kulonwabo ngenxa yokutya okugqithisileyo.
I-EE inyuke ngokulandelelana ukusuka kwi-30 ukuya kwi-22 ° C kwaye yayimalunga ne-30% ephezulu kwi-22 ° C xa kuthelekiswa ne-30 ° C (Umfanekiso 1a, b).Ireyithi yokutshintshiselana ngokuphefumula (RER) yayizimeleyo kwiqondo lokushisa (Umfanekiso 1c, d).Ukutya kwakuhambelana ne-EE dynamics kwaye kwanda ngokuhla kweqondo lokushisa (kwaye ~ 30% ephezulu kwi-22 ° C xa kuthelekiswa ne-30 ° C (Fig. 1e, f) Ukungena kwamanzi. 1g).
Iigundane zamadoda (i-C57BL / 6J, iiveki ze-20 ubudala, izindlu zomntu ngamnye, n = 7) zigcinwe kwii-cages ze-metabolic kwi-22 ° C. kwiveki enye ngaphambi kokuqala kwesifundo.Kwiintsuku ezimbini emva kokuqokelela idatha yangasemva, iqondo lokushisa liphakanyiswe kwi-2 ° C ukunyuka kwi-06: iiyure ze-00 ngosuku (ukuqala kwesigaba sokukhanya).Idatha inikwe njengentsingiselo ± impazamo eqhelekileyo yentsingiselo, kwaye isigaba esimnyama (18:00–06:00 h) simelwe yibhokisi engwevu.a Inkcitho yamandla (kcal/h), b Iyonke inkcitho yamandla kumaqondo obushushu ahlukeneyo (kcal/24 h), c Izinga lokutshintshiselana ngokuphefumla (VCO2/VO2: 0.7–1.0), d Mean RER ekukhanyeni nasekumnyama (VCO2 / VO2) isigaba (ixabiso elinguziro lichazwa njengo-0.7).Ukuthathwa kokutya okongezelekayo (g), f I-24h yokutya iyonke, g 24h iyonke yamanzi ethathiweyo (ml), h 24h iyonke yokuthatha amanzi, inqanaba lomsebenzi elongezelekayo (m) kunye j inqanaba lomsebenzi lilonke (m/24h) .).Iimpuku zagcinwa kubushushu obuchaziweyo iiyure ezingama-48.Idatha eboniswe kwi-24, i-26, i-28 kunye ne-30 ° C ibhekisela kwiiyure zokugqibela ze-24 zomjikelezo ngamnye.Iimpuku zahlala zondliwa ngalo lonke ixesha lokufunda.Ukubaluleka kwamanani kwavavanywa ngemilinganiselo ephindaphindiweyo ye-ANOVA yendlela enye elandelwa luvavanyo lokuthelekisa oluninzi lukaTukey.Iinkwenkwezi zibonisa ukubaluleka kwexabiso lokuqala le-22 ° C, i-shading 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 ngalo lonke ixesha lovavanyo (iiyure eziyi-0-192).n = 7.
Njengoko kwimeko yeegundane zobunzima obuqhelekileyo, i-EE yanda ngokulandelelana kunye nokunciphisa ukushisa, kwaye kule meko, i-EE nayo yayimalunga ne-30% ephezulu kwi-22 ° C xa kuthelekiswa ne-30 ° C (Umfanekiso 2a, b).I-RER ayizange itshintshe kumaqondo ahlukeneyo (Umfanekiso 2c, d).Ngokwahlukileyo kwiigundane zobunzima obuqhelekileyo, ukutya kwakungahambelani ne-EE njengomsebenzi wokushisa kwegumbi.Ukutya kokutya, ukuthathwa kwamanzi, kunye nenqanaba lomsebenzi lixhomekeke kwiqondo lokushisa (Imifanekiso 2e-j).
Indoda (i-C57BL / 6J, iiveki ze-20) iigundane ze-DIO zahlaliswa ngabanye kwii-cages ze-metabolic kwi-22 ° C. kwiveki enye ngaphambi kokuqala kwesifundo.Iigundane zingasebenzisa i-45% ye-HFD ad libitum.Emva kokulungelelaniswa kweentsuku ezimbini, idatha yesiseko yaqokelelwa.Emva koko, iqondo lokushisa liphakanyiswe ngokunyuka kwe-2 ° C yonke imihla ngo-06:00 (ukuqala kwesigaba sokukhanya).Idatha inikwe njengentsingiselo ± impazamo eqhelekileyo yentsingiselo, kwaye isigaba esimnyama (18:00–06:00 h) simelwe yibhokisi engwevu.a Inkcitho yamandla (kcal/h), b Iyonke inkcitho yamandla kumaqondo obushushu ahlukeneyo (kcal/24 h), c Izinga lokutshintshiselana ngokuphefumla (VCO2/VO2: 0.7–1.0), d Mean RER ekukhanyeni nasekumnyama (VCO2 / VO2) isigaba (ixabiso elinguziro lichazwa njengo-0.7).Ukuthathwa kokutya okongezelekayo (g), f I-24h yokutya iyonke, g 24h iyonke yamanzi ethathiweyo (ml), h 24h iyonke yokuthatha amanzi, inqanaba lomsebenzi elongezelekayo (m) kunye j inqanaba lomsebenzi lilonke (m/24h) .).Iimpuku zagcinwa kubushushu obuchaziweyo iiyure ezingama-48.Idatha eboniswe kwi-24, i-26, i-28 kunye ne-30 ° C ibhekisela kwiiyure zokugqibela ze-24 zomjikelezo ngamnye.Iigundane zigcinwe kwi-45% ye-HFD de kube sekupheleni kophononongo.Ukubaluleka kwamanani kwavavanywa ngemilinganiselo ephindaphindiweyo ye-ANOVA yendlela enye elandelwa luvavanyo lokuthelekisa oluninzi lukaTukey.Iinkwenkwezi zibonisa ukubaluleka kwexabiso lokuqala le-22 ° C, i-shading 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. *Р<0,05, ***Р<0,001, ****Р<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. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Amaxabiso aphakathi abalwa ngalo lonke ixesha lovavanyo (iiyure eziyi-0-192).n = 7.
Kolunye uthotho lweemvavanyo, sivavanye isiphumo sobushushu be-ambient kwiiparamitha ezifanayo, kodwa ngeli xesha phakathi kwamaqela eempuku ezihlala zigcinwa kubushushu obuthile.Iigundane zahlulwa zibe ngamaqela amane ukunciphisa utshintsho lwamanani kwintsingiselo kunye nokuphambuka okusemgangathweni kobunzima bomzimba, amanqatha, kunye nobunzima bomzimba obuqhelekileyo (Umfanekiso 3a-c).Emva kweentsuku ezisi-7 zokuqhelaniswa, iintsuku ezi-4.5 zeEE zarekhodwa.I-EE ichaphazeleka kakhulu kubushushu be-ambient zombini ngexesha lemini nobusuku (Fig. 3d), kwaye inyuka ngokulandelelana njengoko ubushushu buhla ukusuka kwi-27.5 ° C ukuya kwi-22 ° C (Fig. 3e).Xa kuthelekiswa namanye amaqela, i-RER yeqela le-25 ° C yancitshiswa ngandlela-thile, kwaye kwakungekho nantlukwano phakathi kwamaqela asele (umzobo 3f, g).Ukuthathwa kokutya okuhambelana nepateni ye-EE kunyuke malunga ne-30% kwi-22 ° C xa kuthelekiswa ne-30 ° C (Fig. 3h, i).Ukusetyenziswa kwamanzi kunye namanqanaba omsebenzi awazange ahluke kakhulu phakathi kwamaqela (Umfanekiso 3j, k).Ukubonakaliswa kwamaqondo okushisa ahlukeneyo ukuya kwii-33 iintsuku akuzange kuholele ekuhlukeni kobunzima bomzimba, ubunzima bobunzima, kunye nobunzima bamanqatha phakathi kwamaqela (umzobo we-3n-s), kodwa kubangele ukuhla kobunzima bomzimba obunzima malunga ne-15% xa kuthelekiswa amanqaku azichazayo (umzobo 3n-s).3b, r, c)) kunye ne-fat mass yanda ngamaxesha angaphezu kwama-2 (ukusuka ~ 1 g ukuya ku-2-3 g, umzobo 3c, t, c).Ngelishwa, ikhabhinethi ye-30 ° C ineempazamo zokulinganisa kwaye ayikwazi ukubonelela ngedatha echanekileyo ye-EE kunye ne-RER.
- Ubunzima bomzimba (a), ubunzima bokubhitya (b) kunye nobunzima bamafutha (c) emva kweentsuku ezisi-8 (usuku olunye phambi kokudluliselwa kwinkqubo ye-SABLE).d Ukusetyenziswa kwamandla (kcal / h).e I-avareji yokusetyenziswa kwamandla (0-108 iiyure) kumaqondo obushushu ahlukeneyo (kcal/24 iiyure).f Umlinganiselo wotshintshiselwano ngokuphefumla (RER) (VCO2/VO2).g Kuthetha iRER (VCO2/VO2).h Ukutya okupheleleyo kokutya (g).i Mean ukutya kokutya (g/24 iiyure).j Usetyenziso lwamanzi lulonke (ml).k Umlinganiselo wokusetyenziswa kwamanzi (ml/24 h).l Inqanaba lomsebenzi elongezelekayo (m).m Umyinge womgangatho womsebenzi (m/24 h).ubunzima bomzimba ngosuku lwe-18, o utshintsho kubunzima bomzimba (ukusuka kwi-8th ukuya kwi-18th day), ubunzima obuncinci ngosuku lwe-18, q utshintsho kubunzima obuncinci (ukusuka kwi-8th ukuya kwi-18th day), ubunzima bobunzima ngosuku lwe-18 , kunye nokutshintsha kwi-fat mass (ukusuka kwi-8 ukuya kwiintsuku ze-18).Ukubaluleka kwezibalo zamanyathelo aphindaphindiweyo kwavavanywa yi-Oneway-ANOVA elandelwa yi-Tukey yokuvavanya ukuthelekisa okuninzi. *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 iboniswe njengentsingiselo + impazamo eqhelekileyo yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe iibhokisi ezingwevu.Amachaphaza kwiihistograms amele iimpuku ezizimeleyo.Amaxabiso aphakathi abalwa ngalo lonke ixesha lovavanyo (iiyure ze-0-108).n = 7.
Iigundane zihambelana nesisindo somzimba, ubunzima obunzima, kunye ne-fat mass at baseline (Figs. 4a-c) kwaye zigcinwe kwi-22, 25, 27.5, kunye ne-30 ° C njengezifundo kunye neegundane eziqhelekileyo..Xa kuthelekiswa amaqela eempuku, ubudlelwane phakathi kwe-EE kunye nobushushu bubonise ubudlelwane obufanayo bomgca kunye nobushushu ngokuhamba kwexesha kwiigundane ezifanayo.Ngaloo ndlela, iigundane ezigcinwe kwi-22 ° C zidla malunga ne-30% yamandla ngaphezu kweegundane ezigcinwe kwi-30 ° C (Umfanekiso 4d, e).Xa ufunda iziphumo kwizilwanyana, ukushisa akuzange kuhlale kuchaphazela i-RER (Umfanekiso 4f, g).Ukutya kokutya, ukungena kwamanzi, kunye nomsebenzi awuzange uchaphazeleke kakhulu ngamaqondo okushisa (Amakhiwane 4h-m).Emva kweentsuku ze-33 zokukhuliswa, iigundane kwi-30 ° C zazinobunzima bomzimba obuphezulu kakhulu kuneegundane kwi-22 ° C (umzobo 4n).Xa kuthelekiswa neendawo zazo ezisisiseko, iimpuku ezikhuliswe kwi-30 ° C zazinobunzima bomzimba obuphezulu kakhulu kuneempuku ezikhuliswe kwi-22 ° C (zithetha ± impazamo eqhelekileyo yentsingiselo: Umzobo 4o).Ubunzima obuphezulu obuphezulu bubangelwa ukwanda kwamafutha (umzobo 4p, q) kunokunyuka kobunzima (umzobo 4r, s).Ngokuhambelana nexabiso eliphantsi le-EE kwi-30 ° C, ukubonakaliswa kweentlobo ezininzi ze-BAT ezandisa umsebenzi / umsebenzi we-BAT wancitshiswa kwi-30 ° C xa kuthelekiswa ne-22 ° C: i-Adra1a, i-Adrb3, kunye ne-Prdm16.Ezinye izakhi zofuzo eziphambili nazo zandisa umsebenzi we-BAT / umsebenzi azizange zichaphazeleke: I-Sema3a (ukulawulwa kwe-neurite ukukhula), i-Tfam (i-mitochondrial biogenesis), i-Adrb1, i-Adra2a, i-Pck1 (i-gluconeogenesis) kunye ne-Cpt1a.Okumangalisayo kukuba, i-Ucp1 kunye ne-Vegf-a, ehambelana nokunyuka komsebenzi we-thermogenic, ayizange iyancipha kwiqela le-30 ° C.Enyanisweni, amanqanaba e-Ucp1 kwiigundane ezintathu ayephezulu kuneqela le-22 ° C, kwaye i-Vegf-a kunye ne-Adrb2 yayiphakanyiswe kakhulu.Xa kuthelekiswa neqela le-22 ° C, iigundane ezigcinwe kwi-25 ° C kunye ne-27.5 ° C zibonise ukuba akukho tshintsho (umzobo owongezelelweyo 1).
- Ubunzima bomzimba (a), ubunzima bokubhitya (b) kunye nobunzima bamafutha (c) emva kweentsuku ezili-9 (usuku olunye phambi kokudluliselwa kwinkqubo ye-SABLE).d Ukusetyenziswa kwamandla (EE, kcal/h).e Umyinge wokusetyenziswa kwamandla (iiyure ezingama-0-96) kumaqondo obushushu ahlukeneyo (kcal/24 iiyure).f Umlinganiselo wotshintshiselwano ngokuphefumla (RER, VCO2/VO2).g Kuthetha iRER (VCO2/VO2).h Ukutya okupheleleyo kokutya (g).i Mean ukutya kokutya (g/24 iiyure).j Usetyenziso lwamanzi lulonke (ml).k Umlinganiselo wokusetyenziswa kwamanzi (ml/24 h).l Inqanaba lomsebenzi elongezelekayo (m).m Umyinge womgangatho womsebenzi (m/24 h).n Ubunzima bomzimba ngosuku lwama-23 (g), o Ukutshintsha kobunzima bomzimba, p Ubunzima obubhityileyo, q Ukutshintsha kobunzima obubhityileyo (g) ngosuku lwama-23 xa kuthelekiswa nosuku lwe-9, Ukutshintsha kobunzima bamafutha (g) ngeentsuku ezingama-23, amafutha ubunzima (g) xa kuthelekiswa nosuku lwesi-8, usuku lwama-23 xa kuthelekiswa nosuku lwe-8.Ukubaluleka kwezibalo zamanyathelo aphindaphindiweyo kwavavanywa yi-Oneway-ANOVA elandelwa yi-Tukey yokuvavanya ukuthelekisa okuninzi. *P <0.05, ***P <0.001, ****P <0.0001. *P <0.05, ***P <0.001, ****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<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. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Idatha iboniswe njengentsingiselo + impazamo eqhelekileyo yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe iibhokisi ezingwevu.Amachaphaza kwiihistograms amele iimpuku ezizimeleyo.Amaxabiso aphakathi abalwa kulo lonke ixesha lokulinga (0-96 iiyure).n = 7.
Njengabantu, iimpuku zihlala zenza i-microenvironments ukunciphisa ilahleko yobushushu kwindalo esingqongileyo.Ukulinganisa ukubaluleka kokusingqongileyo kwi-EE, siye savavanya i-EE kuma-22, 25, 27.5, kunye nama-30 ° C, kunye okanye ngaphandle koonogada besikhumba kunye nempahla yokuzalela.Kwi-22 ° C, ukongezwa kwezikhumba eziqhelekileyo kunciphisa i-EE malunga ne-4%.Ukongezwa okulandelayo kwezinto zokuzalela kunciphise iEE nge-3-4% (Umfanekiso 5a,b).Akukho tshintsho lubalulekileyo kwi-RER, ukutya, ukungena kwamanzi, okanye amanqanaba omsebenzi abonwa kunye nokongezwa kwezindlu okanye izikhumba + zokulala (Umfanekiso 5i-p).Ukongezwa kwesikhumba kunye nezinto zokuzalela nazo zanciphisa kakhulu i-EE kwi-25 kunye ne-30 ° C, kodwa iimpendulo zazincinci.Kwi-27.5 ° C akukho mahluko ubonwe.Ngokucacileyo, kule mvavanyo, i-EE yehla ngokunyuka kweqondo lokushisa, kule meko malunga ne-57% ephantsi kwe-EE kwi-30 ° C xa kuthelekiswa ne-22 ° C (umzobo 5c-h).Uhlalutyo olufanayo lwenziwa kuphela kwisigaba sokukhanya, apho i-EE yayisondele kwisantya se-basal metabolic, ekubeni kulo mzekelo iigundane ziphumle kakhulu esikhumbeni, okubangelwa ukulinganisa ubukhulu beempembelelo kumaqondo okushisa ahlukeneyo (i-Supplementary Fig. 2a-h) .
Idatha yeempuku ezisuka kwindawo yokuhlala kunye nempahla yokuzalela (ibhlowu emnyama), ikhaya kodwa akukho mpahla yokuzalela (ibhlowu ekhanyayo), kunye nempahla yasekhaya kunye nendlwane (i-orenji).Ukusetyenziswa kwamandla (EE, kcal / h) kumagumbi a, c, e kunye ne-g kwi-22, 25, 27.5 kunye ne-30 °C, b, d, f kunye ne-h ithetha i-EE (kcal / h).ip Idatha yeempuku ezigcinwe ku-22°C: isantya sokuphefumla (RER, VCO2/VO2), j mean RER (VCO2/VO2), k ukuthathwa kokutya okuqokelelweyo (g), l umyinge wokutya (g/24 h), m Ukuthathwa kwamanzi xa iyonke (mL), kumyinge wokuthatha amanzi yi-AUC (mL/24h), o umsebenzi uwonke (m), umyinge womyinge womsebenzi (m/24h).Idatha iboniswe njengentsingiselo + impazamo eqhelekileyo yentsingiselo, isigaba esimnyama (18: 00-06: 00 h) simelwe iibhokisi ezingwevu.Amachaphaza kwiihistograms amele iimpuku ezizimeleyo.Ukubaluleka kwezibalo zamanyathelo aphindaphindiweyo kwavavanywa yi-Oneway-ANOVA elandelwa yi-Tukey yokuvavanya ukuthelekisa okuninzi. *P <0.05, **P <0.01. *P <0.05, **P <0.01. * Р<0,05, **Р<0,01. *P<0.05, **P<0.01. *P <0.05,**P <0.01. *P <0.05,**P <0.01. * Р<0,05, **Р<0,01. *P<0.05, **P<0.01.Amaxabiso aphakathi abalwe kulo lonke ixesha lovavanyo (iiyure ezingama-0-72).n = 7.
Kwiigundane zobunzima obuqhelekileyo (iiyure ze-2-3 zokuzila ukutya), ukukhuliswa kwamaqondo ahlukeneyo akuzange kubangele ukungafani okukhulu kwi-plasma concentrations ye-TG, i-3-HB, i-cholesterol, i-ALT, kunye ne-AST, kodwa i-HDL njengomsebenzi weqondo lokushisa.Umzobo 6a-e).Ukuzila ukutya kwe-plasma ye-leptin, i-insulin, i-C-peptide, kunye ne-glucagon nayo ayizange ihluke phakathi kwamaqela (Amanani 6g-j).Ngomhla wokuvavanya ukunyamezela kwe-glucose (emva kweentsuku ze-31 kumaqondo ahlukeneyo), inqanaba lesiseko se-glucose yegazi (iiyure ezingama-5-6 zokuzila ukutya) malunga ne-6.5 mM, kungekho mahluko phakathi kwamaqela. Ukulawulwa kwe-glucose yomlomo kwandisa i-blood concentrations kakhulu kuwo onke amaqela, kodwa zombini i-peak concentration kunye ne-incremental area under the curves (iAUCs) (15-120 min) yayiphantsi kwiqela leempuku ezigcinwe kwi-30 ° C (ixesha ngalinye: P <0.05–P <0.0001, Umfanekiso 6k, l) xa kuthelekiswa neempuku ezigcinwe kwi-22, 25 kunye ne-27.5 °C (ezingahlukanga phakathi komnye). Ukulawulwa kwe-glucose yomlomo kwandisa i-blood concentrations kakhulu kuwo onke amaqela, kodwa zombini i-peak concentration kunye ne-incremental area under the curves (iAUCs) (15-120 min) yayiphantsi kwiqela leempuku ezigcinwe kwi-30 ° C (ixesha ngalinye: P <0.05-P <0.0001, Umfanekiso 6k, l) xa kuthelekiswa neempuku ezigcinwe kwi-22, 25 kunye ne-27.5 ° C (ezingahlukanga phakathi komnye nomnye). Пероральное введение глюкозы значительно повышало концентрацию в крови во всех группах, но как пиковая концентрация выми (iAUC) (15–120 мин) были ниже в группе мышей, содержащихся при 30 °C (отдельные временные точки: P < 0,05–P < 0,0001, рис 6k, l) по сравнению с мышами, содержащимися при 22, 25 и 27,5 ° C (которые не различались межой со). Ukulawulwa komlomo we-glucose ngokuphawulekayo kwandisa i-blood glucose concentrations kuwo onke amaqela, kodwa zombini i-peak concentration kunye ne-incremental area under the curves (iAUC) (15-120 min) yayiphantsi kwiqela le-30 ° C leegundane (ixesha elihlukeneyo: P <0.05-) P <0.0001, Umzobo 6k, l) xa kuthelekiswa neegundane ezigcinwe kwi-22, 25 kunye ne-27.5 ° C (ezingahlukanga omnye komnye).口服葡萄糖的给药显着增加了所有组的血糖浓度，但在30 °C 饲养的小鼠组中，峰值浓度和时候(1) -120 分钟) 均较低（各个时间点:P <0.05–P <0.0001,图6k,l）与饲养在22,25 kunye27.5°C 的小鼠（彼此之间沒有差异）相比。口服 葡萄糖 的 给 药 显着 了 所有组 的 血糖 浓度 但 在 在 30 ° C 饲养 小鼠组 中平积 面积 (IAUC) (15-120 分钟) 均 较 低 各 个 点 点 点Umgangatho:P <0.05–P <0.0001,图6k,l）与饲养在22,25和27.5°C 的小鼠（彼此之间沒有差弸比).Ukulawulwa komlomo we-glucose ngokuphawulekayo kwandisa i-blood concentrations ye-blood glucose kuwo onke amaqela, kodwa zombini i-concentration ye-peak kunye nommandla ophantsi kwe-curve (iAUC) (i-15-120 min) yayiphantsi kwiqela le-30 ° C-elondliwe (amaxesha onke).: P < 0,05–P < 0,0001, рис. : P <0.05-P <0.0001, Umzobo.6l, l) xa kuthelekiswa neempuku ezigcinwe kwi-22, i-25 kunye ne-27.5 ° C (akukho mmahluko omnye komnye).
I-Plasma concentrations ye-TG, i-3-HB, i-cholesterol, i-HDL, i-ALT, i-AST, i-FFA, i-glycerol, i-leptin, i-insulin, i-C-peptide, kunye ne-glucagon iboniswa kwi-DIO (al) yendoda endala emva kweentsuku ze-33 zokutya kwiqondo lokushisa elibonakalisiweyo. .Iimpuku azizange zondliwe kwiiyure ezingama-2-3 ngaphambi kokuba kuthathwe isampulu yegazi.Okungafaniyo kwakuyimvavanyo yokunyamezela i-glucose yomlomo, eyenziwa iintsuku ezimbini ngaphambi kokuphela kwesifundo kwiigundane ezizila ukutya iiyure ezingama-5-6 kwaye zigcinwe kwiqondo lokushisa elifanelekileyo kwiintsuku ezingama-31.Iigundane zacelwa umngeni nge-2 g / kg ubunzima bomzimba.Ummandla ongaphantsi kwedatha ye-curve (L) ichazwa njengedatha eyongezelelweyo (iAUC).Idatha inikezelwe njengentsingiselo ± SEM.Amachaphaza amele iisampulu nganye. *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<0.0001, 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 <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7.
Kwiigundane ze-DIO (kwaye zizila ukutya kwiiyure ze-2-3), i-cholesterol ye-plasma, i-HDL, i-ALT, i-AST, kunye ne-FFA yogxininiso ayizange ihluke phakathi kwamaqela.Zombini i-TG kunye ne-glycerol ziphakanyiswe kakhulu kwiqela le-30 ° C xa kuthelekiswa neqela le-22 ° C (Amanani 7a-h).Ngokwahlukileyo, i-3-GB yayimalunga ne-25% ephantsi kwi-30 ° C xa kuthelekiswa ne-22 ° C (Umfanekiso 7b).Ngaloo ndlela, nangona iigundane zigcinwe kwi-22 ° C zine-balance balance yamandla, njengoko kucetyiswa kukufumana ubunzima, ukuhlukana kwi-plasma concentrations ye-TG, i-glycerol, kunye ne-3-HB ibonisa ukuba iigundane kwi-22 ° C xa isampuli yayingaphantsi kwe-22 °. C.°C.Iimpuku ezikhuliswe kwi-30 °C bezikwimo enzima kakhulu.Ngokuhambelana nale nto, ugxininiso lwesibindi se-glycerol kunye ne-TG, kodwa kungekhona i-glycogen kunye ne-cholesterol, yayiphezulu kwiqela le-30 ° C (i-Supplementary Fig. 3a-d).Ukuphanda ukuba iqondo lokushisa elixhomekeke kwi-lipolysis (njengoko lilinganiswe yi-plasma TG kunye ne-glycerol) sisiphumo sotshintsho lwangaphakathi kwi-epididymal okanye i-inguinal fat, sikhuphe izicubu ze-adipose kwezi venkile ekupheleni kophononongo kunye ne-quantified free fatty acid ex. vivo.kunye nokukhululwa kwe-glycerol.Kuwo onke amaqela okulinga, iisampulu zezicubu ze-adipose ezivela kwi-epididymal kunye ne-inguinal depot zibonise ubuncinane ukunyuka okuphindwe kabini kwimveliso ye-glycerol kunye ne-FFA ekuphenduleni ukuvuselela i-isoproterenol (i-Supplementary Fig. 4a-d).Nangona kunjalo, akukho mpembelelo yokushisa kwegobolondo kwi-basal okanye i-isoproterenol-stimulated lipolysis yafunyanwa.Ngokuhambelana nobunzima bomzimba kunye nobunzima bomzimba, amanqanaba e-plasma leptin ayephezulu kakhulu kwiqela le-30 ° C kuneqela le-22 ° C (Umfanekiso 7i).Ngokuchasene noko, amanqanaba e-plasma ye-insulin kunye ne-C-peptide awazange ahluke phakathi kwamaqela okushisa (umzobo 7k, k), kodwa i-plasma glucagon ibonise ukuxhomekeka kwiqondo lokushisa, kodwa kule meko phantse i-22 ° C kwiqela elichaseneyo liphindwe kabini. ukuya kuma-30°C.UKUSUKA.Iqela C (umzobo 7l).I-FGF21 ayizange ihluke phakathi kwamaqela ahlukeneyo obushushu (Umfanekiso we-7m).Ngomhla we-OTT, isiseko se-glucose yegazi malunga ne-10 mM kwaye ayizange ihluke phakathi kweegundane ezigcinwe kumaqondo okushisa ahlukeneyo (Umfanekiso 7n).Ukulawulwa komlomo kweglucose yonyusa amanqanaba eglucose yegazi kwaye kwanda kakhulu kuwo onke amaqela ekugxininiseni malunga ne-18 mM 15 imizuzu emva kokudosa.Kwakungekho nantlukwano ebalulekileyo kwi-iAUC (i-15-120 min) kunye nokugxininiswa kumanqaku exesha elihlukeneyo emva kwe-dose (15, 30, 60, 90 kunye ne-120 min) (Umfanekiso 7n, o).
I-Plasma concentrations ye-TG, i-3-HB, i-cholesterol, i-HDL, i-ALT, i-AST, i-FFA, i-glycerol, i-leptin, i-insulin, i-C-peptide, i-glucagon, kunye ne-FGF21 iboniswe kwi-DIO (ao) yamadoda omdala emva kweentsuku ze-33 zokutya.ubushushu obuchaziweyo.Iimpuku azizange zondliwe kwiiyure ezingama-2-3 ngaphambi kokuba kuthathwe isampulu yegazi.Uvavanyo lokunyamezela i-glucose yomlomo lwaluhlukile njengoko lwenziwa kwi-dose ye-2 g / kg yesisindo somzimba iintsuku ezimbini ngaphambi kokuphela kophando kwiigundane ezizila ukutya kwiiyure ze-5-6 kwaye zigcinwe kwiqondo lokushisa elifanelekileyo kwiintsuku ze-31.Indawo ephantsi kwedatha yegophe (o) iboniswa njengedatha eyongezelelweyo (iAUC).Idatha inikezelwe njengentsingiselo ± SEM.Amachaphaza amele iisampulu nganye. *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<0.0001, 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 <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7.
Ukudluliselwa kwedatha yeempuku ebantwini ngumba ontsonkothileyo odlala indima ephambili ekutolikeni ukubaluleka koqwalaselo kumxholo wophando lomzimba kunye nolwekhemesti.Ngenxa yezizathu zoqoqosho kunye nokuququzelela uphando, iimpuku zihlala zigcinwa kwiqondo lobushushu elingaphantsi kwendawo yazo ye-thermoneutral, okukhokelela ekusebenzeni kweenkqubo ezahlukeneyo zembuyekezo yefiziyoloji ezonyusa isantya semetabolism kwaye zinokuthi ziphazamise ukuguqulelwa9.Ke, ukuvezwa kweempuku kubanda kunokwenza iimpuku zixhathise ukutyeba okubangelwa kukutya kwaye kunokuthintela i-hyperglycemia kwiimpuku ezinyangelwe yi-streptozotocin ngenxa yokwanda kokuthuthwa kweglucose engaxhomekekanga kwi-insulin.Nangona kunjalo, akukacaci ukuba kungakanani ukuvezwa ixesha elide kumaqondo obushushu ahlukeneyo (ukusuka kwigumbi ukuya kwi-thermoneutral) kuchaphazela amandla ahlukeneyo e-homeostasis yeempuku ezinobunzima obuqhelekileyo (ekutyeni) kunye neempuku ze-DIO (kwi-HFD) kunye neeparamitha zemetabolism, kunye nobungakanani. apho bakwazi ukulinganisa ukunyuka kwe-EE kunye nokunyuka kokutya kokutya.Uphononongo olunikwe kweli nqaku lujolise ekuziseni ingcaciso ethile kwesi sihloko.
Sibonisa ukuba kubunzima obuqhelekileyo beempuku zabantu abadala kunye neempuku ze-DIO eziyindoda, i-EE inxulumene ngokungafaniyo nobushushu begumbi phakathi kwe-22 kunye ne-30 ° C.Ngoko ke, iEE kuma-22°C yayimalunga nama-30% ngaphezulu kwe-30°C.kuzo zombini iimodeli zempuku.Nangona kunjalo, umahluko obalulekileyo phakathi kweegundane zobunzima obuqhelekileyo kunye neegundane ze-DIO kukuba ngelixa iigundane zobunzima obuqhelekileyo zihambelana ne-EE kumaqondo okushisa aphantsi ngokulungelelanisa ukuthathwa kokutya ngokufanelekileyo, ukutya kweegundane ze-DIO kwahluka kumanqanaba ahlukeneyo.Amaqondo obushushu ophononongo ayefana.Emva kwenyanga enye, iimpuku ze-DIO ezigcinwe kwi-30 ° C zafumana ubunzima bomzimba kunye nobunzima obuninzi kuneempuku ezigcinwe kwi-22 ° C, ngelixa abantu abaqhelekileyo bagcinwe kubushushu obufanayo kwaye ngexesha elifanayo abazange bakhokele kwifiva.umahluko oxhomekeke kubunzima bomzimba.iimpuku zobunzima.Xa kuthelekiswa namaqondo obushushu kufutshane ne-thermoneutral okanye kwiqondo lobushushu begumbi, ukukhula kwiqondo lobushushu begumbi kubangele i-DIO okanye iimpuku ezinobunzima obuqhelekileyo kukutya okunamafutha aphezulu kodwa hayi kubunzima obuqhelekileyo bokutya kwempuku ukufumana ubunzima obuncinci.umzimba.Ixhaswe zezinye izifundo17,18,19,20,21 kodwa hayi zonke22,23.
Ikhono lokudala i-microenvironment ukunciphisa ukulahleka kobushushu kucatshangelwa ukuguqula ukungathathi hlangothi kwe-thermal ukuya kwesobunxele8, 12. Kwisifundo sethu, zombini ukongezwa kwezinto zokuzalela kunye nokufihla ukunciphisa i-EE kodwa akuzange kubangele ukungathathi hlangothi kwe-thermal ukuya kwi-28 ° C.Ngaloo ndlela, idatha yethu ayixhasi ukuba indawo ephantsi ye-thermoneutrality kwiigundane ezikhulile ezinedolo elilodwa, kunye okanye ngaphandle kwezindlu eziphuculwe ngokusingqongileyo, kufuneka zibe yi-26-28 ° C njengoko kubonisiwe8,12, kodwa ixhasa ezinye izifundo ezibonisa ukushisa kwe-thermoneutrality.amaqondo obushushu e-30 ° C kwindawo ephantsi iimice7, 10, 24. Ukunyanzela imicimbi, indawo ye-thermoneutral kwiigundane ibonakaliswe ukuba ayinayo i-static emini njengoko iphantsi ngexesha lokuphumla (ukukhanya) isigaba, mhlawumbi ngenxa yekhalori ephantsi. imveliso ngenxa yomsebenzi kunye nokutya-induced thermogenesis.Ngaloo ndlela, kwisigaba sokukhanya, indawo ephantsi yokungathathi hlangothi kwe-thermal ijika ibe ngu- ~ 29 ° С, kwaye kwinqanaba elimnyama, ~ 33 ° С25.
Ekugqibeleni, ubudlelwane phakathi kobushushu be-ambient kunye nokusetyenziswa kwamandla apheleleyo kugqitywa ngokuchithwa kobushushu.Kulo mongo, umlinganiselo wendawo ukuya kumthamo yinto ebalulekileyo yokumisela ukuvakalelwa kwe-thermal, echaphazela ukutshatyalaliswa kobushushu (ummandla ongaphezulu) kunye nokuveliswa kobushushu (umthamo).Ukongeza kwindawo engaphezulu, ukuhanjiswa kobushushu kukwamiselwa ngokufakwa kwe-insulation (isantya sokuhanjiswa kobushushu).Kubantu, ubunzima bamafutha bunokunciphisa ilahleko yobushushu ngokudala umqobo wokukhusela kwigobolondo lomzimba, kwaye kuye kwacetyiswa ukuba ubunzima be-fat bukwabalulekile ekufakweni kwe-thermal kwiimpuku, ukunciphisa indawo ye-thermoneutral kunye nokunciphisa uvakalelo lobushushu ngaphantsi kwendawo engathathi hlangothi ye-thermal ( ukuthambeka kwegophe).ubushushu be-ambient xa kuthelekiswa neEE)12.Uphononongo lwethu aluzange lwenzelwe ukuvavanya ngokuthe ngqo olu lwalamano lubekayo ngenxa yokuba idatha yokwakheka komzimba iqokelelwe iintsuku ze-9 ngaphambi kokuba idatha yenkcitho yamandla iqokelelwe kwaye ngenxa yokuba ubunzima be-fat abuzange buzinzile kulo lonke uphando.Nangona kunjalo, ekubeni ubunzima obuqhelekileyo kunye neegundane ze-DIO zine-30% ephantsi kwe-EE kwi-30 ° C ngaphezu kwe-22 ° C nangona ubuncinane i-5-fold umehluko kubunzima be-fat mass, idatha yethu ayixhasi ukuba ukukhuluphala kufuneka kubonelele i-insulation esisiseko.factor, ubuncinane hayi kuluhlu lobushushu obuphandwayo.Oku kuhambelana nezinye izifundo ezilungiselelwe ngcono ukuphonononga le4,24.Kwezi zifundo, umphumo wokukhusela ukukhuluphala wawuncinci, kodwa uboya bufunyenwe bubonelela nge-30-50% ye-thermal insulation epheleleyo4,24.Nangona kunjalo, kwiigundane ezifileyo, ukuhanjiswa kwe-thermal kwanda malunga ne-450% ngokukhawuleza emva kokufa, ebonisa ukuba i-insulating effect yoboya iyimfuneko kwiindlela ze-physiological, kubandakanywa ne-vasoconstriction, ukusebenza.Ukongeza kwiiyantlukwano zeentlobo zoboya phakathi kweempuku kunye nabantu, isiphumo esibi sokukhusela ukutyeba kwiimpuku sinokuphenjelelwa yile ngqwalasela ilandelayo: I-insulating factor of human fat mass is especially mediated by subcutaneous fat mass (ukutyeba)26,27.Ngokwesiqhelo kwiimpuku Ngaphantsi kwe-20% yamafutha ezilwanyana ewonke28.Ukongeza, ubunzima be-fat mass abunakuba ngumlinganiselo ongaphantsi kobushushu bomntu, njengoko kuye kwaxoxwa ukuba ukuphuculwa kwe-thermal insulation kuhlanjululwa kukunyuka okungenakuthintelwa kwindawo ephezulu (kwaye ngoko kwanda ukulahleka kobushushu) njengoko ubunzima bamafutha bunyuka..
Kwiigundane zobunzima obuqhelekileyo, i-plasma yokuzila ukutya kwe-TG, i-3-HB, i-cholesterol, i-HDL, i-ALT, kunye ne-AST ayizange itshintshe kumaqondo okushisa ahlukeneyo malunga neeveki ze-5, mhlawumbi ngenxa yokuba iigundane zazikwimeko efanayo yokulinganisela kwamandla.zazifana ngobunzima kunye nokwakheka komzimba njengoko ekupheleni kophononongo.Ngokuhambelana nokufana kwe-fat mass, kwakungekho nantlukwano kumanqanaba e-plasma leptin, okanye kwi-insulin yokuzila, i-C-peptide kunye ne-glucagon.Imiqondiso emininzi ifunyenwe kwiimpuku ze-DIO.Nangona iimpuku kwi-22 ° C nazo zazingenalo ibhalansi yamandla engalunganga ngokubanzi kulo mbuso (njengoko zaye zafumana ubunzima), ekupheleni kophononongo zaziswele amandla ngakumbi xa kuthelekiswa neempuku ezikhuliswe kwi-30 ° C, kwiimeko ezinje. iiketoni eziphezulu.ukuveliswa ngumzimba (i-3-GB) kunye nokuncipha kwe-concentration ye-glycerol kunye ne-TG kwi-plasma.Nangona kunjalo, umahluko oxhomekeke kwiqondo lobushushu kwi-lipolysis awubonakali ngathi sisiphumo sotshintsho lwangaphakathi kwi-epididymal okanye kwi-inguinal fat, njengotshintsho kwimbonakalo ye-adipohormone-responsive lipase, kuba i-FFA kunye ne-glycerol ekhutshiweyo kumafutha athathwe kwezi depo ziphakathi kobushushu. amaqela afana omnye komnye.Nangona asizange siphande ithoni yovelwano kuphononongo lwangoku, abanye baye bafumanisa ukuba (ngokusekelwe kwisantya sentliziyo kunye noxinzelelo lwe-arterial) luhambelana ngokuhambelana nobushushu be-ambient kwiigundane kwaye bungaphantsi kwe-30 ° C kune-22 ° C 20% C Ngaloo ndlela, ukuhluka okuxhomekeke kwiqondo lokushisa kwithoni enovelwano kunokudlala indima kwi-lipolysis kwisifundo sethu, kodwa ekubeni ukwanda kwethoni yovelwano kukhuthaza kunokuba kuthintele i-lipolysis, ezinye iindlela zinokuthi zichase oku kuncipha kweempuku ezikhuliswe.Indima enokwenzeka ekuqhekekeni kwamafutha omzimba.Ubushushu begumbi.Ngapha koko, inxalenye yesiphumo sokuvuselela ithoni yovelwano kwi-lipolysis ilawulwa ngokungathanga ngqo ngokuthintelwa okuqinileyo kwe-insulin secretion, iqaqambisa isiphumo sokuphazamiseka kwe-insulin kwi-lipolysis30, kodwa kuphononongo lwethu, i-insulin yokuzila ukutya kunye ne-C-peptide ithoni yovelwano kumaqondo obushushu ahlukeneyo. akwanelanga ukuguqula i-lipolysis.Endaweni yoko, sifumanise ukuba iyantlukwano kwisimo samandla yeyona nto inokwenzeka ukuba ibenegalelo kolu mahluko kwiimpuku ze-DIO.Izizathu ezisisiseko ezikhokelela kulawulo olungcono lokutya kunye ne-EE kwiimpuku ezinobunzima obuqhelekileyo zifuna uphononongo oluqhubekayo.Ngokuqhelekileyo, nangona kunjalo, ukutya kulawulwa yi-homeostatic kunye ne-hedonic cues31,32,33.Nangona kukho ingxoxo malunga nokuba yeyiphi imiqondiso emibini ebaluleke kakhulu ngokobungakanani, i-31,32,33 iyaziwa kakuhle ukuba ukusetyenziswa kwexesha elide lokutya okunamafutha amaninzi kukhokelela ekuziphatheni okutya okusekelwe kwizinto zokuzonwabisa okungahambelani noko. i-homeostasis..– ukutya okulawulwayo34,35,36.Ke ngoko, ukonyuka kokuziphatha kwe-hedonic ye-DIO yeempuku eziphathwe nge-45% HFD inokuba sesinye sezizathu zokuba ezi mpuku zingakhange zilinganise ukutya kunye ne-EE.Okubangela umdla kukuba, iyantlukwano kumdla wokutya kunye neehomoni ezilawula iswekile yegazi nazo zabonwa kwiimpuku zeDIO ezilawulwa ngubushushu, kodwa hayi kwiimpuku ezinobunzima obuqhelekileyo.Kwiimpuku ze-DIO, amanqanaba e-plasma leptin anda ngobushushu kunye namanqanaba e-glucagon ehle ngobushushu.Ubungakanani bobushushu obunokuthi buphembelele ngokuthe ngqo lo mahluko lufanele ukufundwa ngakumbi, kodwa kwimeko ye-leptin, ibhalansi yamandla engalunganga kwaye ngaloo ndlela ubunzima obuphantsi bamafutha kwiimpuku kwi-22 ° C ngokuqinisekileyo budlale indima ebalulekileyo, njengoko ubunzima be-fat kunye ne-plasma leptin. inxulumene kakhulu37.Nangona kunjalo, ukutolikwa komqondiso weglucagon kuyadida ngakumbi.Njengakwi-insulin, ukukhutshwa kweglucagon kwakuthintelwe ngamandla kukwanda kwethowuni yovelwano, kodwa ithowuni ephezulu yovelwano yayiqikelelwe ukuba ikwiqela le-22 ° C, elalinelona qondo liphezulu leglucagon kwiplasma.I-insulin yenye i-regulator eqinile ye-plasma glucagon, kunye nokuxhatshazwa kwe-insulin kunye nohlobo lwe-2 yeswekile ihambelana kakhulu nokuzila ukudla kunye ne-postprandial hyperglucagonemia 38,39.Nangona kunjalo, iigundane ze-DIO kwisifundo sethu nazo zazingenangqondo kwi-insulin, ngoko ke oku kwakungenakuba yinto ephambili ekunyuseni kwe-glucagon yokubonisa kwiqela le-22 ° C.Umxholo wamafutha wesibindi unxulumene ngokuqinisekileyo nokunyuka kwe-plasma glucagon concentration, iindlela ezinokuthi zibandakanye ukuxhathisa kwe-glucagon ye-hepatic, ukunciphisa ukuveliswa kwe-urea, ukunyuka kwe-amino acid concentrations, kunye nokunyuka kwe-amino acid-stimulated glucagon secretion40,41, 42.Nangona kunjalo, ekubeni i-extractable concentrations ye-glycerol kunye ne-TG ayizange ihluke phakathi kwamaqela okushisa kwisifundo sethu, le nto ayinakuba yinto enokuthi ibangele ukunyuka kwe-plasma ye-plasma kwiqela le-22 ° C.I-Triiodothyronine (T3) idlala indima ebalulekileyo kwizinga le-metabolic jikelele kunye nokuqaliswa kokukhusela umzimba kwi-hypothermia43,44.Ngaloo ndlela, i-plasma ye-T3 yoxinaniso, mhlawumbi ilawulwa ngeendlela eziphakathi, i-45,46 inyuka kuzo zombini iigundane kunye nabantu phantsi kweemeko ezingaphantsi kwe-thermoneutral47, nangona ukwanda kwabantu kuncinci, okuxhomekeke ngakumbi kwiigundane.Oku kuhambelana nokulahleka kobushushu kokusingqongileyo.Asizange silinganise i-plasma ye-T3 i-concentrations kwisifundo esikhoyo, kodwa ugxininiso lunokuba luphantsi kwiqela le-30 ° C, elinokuthi lichaze umphumo weli qela kumanqanaba e-plasma glucagon, njengoko thina (uhlaziyo lwe-Figure 5a) kunye nabanye baye babonisa ukuba I-T3 yonyusa i-plasma glucagon ngendlela exhomekeke kwidosi.Iihomoni ze-thyroid ziye zaxelwa ukuba zenze i-FGF21 ibonakaliswe esibindini.Njenge-glucagon, i-plasma FGF21 i-concentrations nayo yanda nge-plasma T3 concentrations (i-Supplementary Fig. 5b kunye ne-ref. 48), kodwa xa kuthelekiswa ne-glucagon, i-FGF21 i-plasma concentrations kwisifundo sethu ayizange ichaphazeleke kwiqondo lokushisa.Izizathu ezisisiseko zale ntlukwano zifuna uphononongo olongezelelweyo, kodwa i-T3-driven FGF21 induction kufuneka yenzeke kumanqanaba aphezulu e-T3 exposure xa kuthelekiswa nempendulo yeglucagon eqhutywe yi-T3 (i-Supplementary Fig. 5b).
I-HFD ibonakaliswe ukuba inxulumene kakhulu nokunyamezela ukunyamezela kwe-glucose kunye nokuxhatshazwa kwe-insulin (amanqaku) kwiigundane ezikhuliswe kwi-22 ° C.Nangona kunjalo, i-HFD ayizange idibaniswe nokuba yi-glucose ukunyamezela ukunyamezela okanye ukuxhathisa i-insulin xa ikhulile kwindawo ye-thermoneutral (echazwe apha njenge-28 °C) 19.Kwisifundo sethu, olu lwalamano aluzange luphindwe kwiigundane ze-DIO, kodwa iigundane ezinobunzima obuqhelekileyo zigcinwe kwi-30 ° C ziphucule kakhulu ukunyamezela kwe-glucose.Isizathu salo mahluko sidinga uphononongo olongezelelweyo, kodwa sinokuphenjelelwa kukuba iigundane ze-DIO kwisifundo sethu zazixhathisa i-insulin, kunye ne-plasma yokuzila i-C-peptide concentrations kunye noxinzelelo lwe-insulin amaxesha angama-12-20 aphezulu kuneempuku ezinobunzima obuqhelekileyo.nasegazini kwisisu esingenanto.i-glucose concentrations malunga ne-10 mM (malunga ne-6 mM kubunzima bomzimba obuqhelekileyo), ebonakala ishiya ifestile encinci kuyo nayiphi na imiphumo enokuba yinzuzo yokuvezwa kweemeko ze-thermoneutral ukuphucula ukunyamezela kwe-glucose.Into enokuthi idideke kukuba, ngenxa yezizathu eziphathekayo, i-OGTT iqhutyelwa kwiqondo lokushisa.Ke, iimpuku ezigcinwe kumaqondo obushushu aphezulu zifumana ukothuka okubandayo, okunokuthi kuchaphazele ukufunxwa/ukucocwa kweglucose.Nangona kunjalo, ngokusekwe kugxininiso olufanayo lwe-glucose yegazi lokuzila ukutya kumaqela ahlukeneyo obushushu, utshintsho kwiqondo lobushushu be-ambient lusenokungazichaphazeli kakhulu iziphumo.
Njengoko kukhankanyiwe ngaphambili, kutsha nje kuphawulwe ukuba ukonyusa ubushushu begumbi kunokunciphisa ukusabela okuthile kuxinzelelo olubandayo, olunokuthi lube nombuzo wokudluliselwa kwedatha yemouse ebantwini.Nangona kunjalo, akucaci ukuba leliphi iqondo lobushushu elilelona lifanelekileyo lokugcina iimpuku zilinganisa i-physiology yabantu.Impendulo yalo mbuzo inokuphenjelelwa yinkalo yokufunda kunye nesiphelo esifundwayo.Umzekelo wale nto yimpembelelo yokutya ekuqokeleleni kwamafutha esibindi, ukunyamezela i-glucose kunye nokumelana ne-insulin19.Ngokubhekiselele kwinkcitho yamandla, abanye abaphandi bakholelwa ukuba i-thermoneutrality lelona qondo lobushushu liphezulu lokukhuliswa, njengoko abantu bafuna amandla amancinci ongezelelweyo ukugcina ubushushu bomzimba wabo ongundoqo, kwaye bachaza iqondo lokushisa elinye lomjikelo weempuku zabantu abadala njenge-30 ° C7,10.Abanye abaphandi bakholelwa ukuba amaqondo obushushu anokuthelekiswa nabantu abadla ngokufumana iimpuku zabantu abadala kwelinye idolo yi-23-25 ° C, njengoko befumene i-thermoneutrality ibe yi-26-28 ° C kwaye isekelwe ebantwini ukuba bangaphantsi kwe-3 ° C.iqondo lobushushu labo elisezantsi elibalulekileyo, elichazwa apha njenge-23°C, liyi-8.12 kancinane.Uphononongo lwethu luhambelana nezinye izifundo ezininzi ezichaza ukuba ukungathathi hlangothi kwe-thermal akufezekanga kwi-26-28 ° C4, 7, 10, 11, 24, 25, ebonisa ukuba i-23-25 ° C iphantsi kakhulu.Enye into ebalulekileyo ekufuneka iqwalaselwe malunga nobushushu begumbi kunye ne-thermoneutrality kwiimpuku yindawo enye okanye yeqela.Xa iimpuku zazihlaliswa ngokwamaqela endaweni yokuba zihlaliswe zizodwa, njengoko kuphononongo lwethu, uvakalelo lobushushu lwancitshiswa, mhlawumbi ngenxa yokuxinana kwezilwanyana.Nangona kunjalo, ukushisa kwegumbi kwakusengaphantsi kwe-LTL ye-25 xa amaqela amathathu asetyenziswa.Mhlawumbi umahluko obaluleke kakhulu we-interspecies kulo mbandela ngokubaluleka kobungakanani bomsebenzi we-BAT njengento yokukhusela kwi-hypothermia.Ngaloo ndlela, ngelixa iigundane zihlawulela ukulahlekelwa kweekhalori eziphezulu ngokunyusa umsebenzi we-BAT, ongaphezu kwe-60% EE kwi-5 ° C kuphela, i-51,52 igalelo lomsebenzi we-BAT wabantu kwi-EE yayiphezulu kakhulu, incinci kakhulu.Ngoko ke, ukunciphisa umsebenzi we-BAT kunokuba yindlela ebalulekileyo yokwandisa ukuguqulelwa komntu.Ukulawulwa komsebenzi we-BAT kuyinkimbinkimbi kodwa ihlala idibene nemiphumo edibeneyo yokuvuselela i-adrenergic, i-hormone ye-thyroid kunye ne-UCP114,54,55,56,57 ibonakaliso.Idatha yethu ibonisa ukuba ukushisa kufuneka kuphakanyiswe ngaphezu kwe-27.5 ° C xa kuthelekiswa neegundane kwi-22 ° C ukuze kubonwe ukungafani kwintetho ye-BAT ejongene nokusebenza / ukusebenza.Nangona kunjalo, ulwahlulo olufunyenwe phakathi kwamaqela kwi-30 kunye ne-22 ° C aluzange lubonise ukwanda komsebenzi we-BAT kwiqela le-22 ° C kuba i-Ucp1, i-Adrb2 kunye ne-Vegf-a yayiphantsi kweqela le-22 ° C.Oyena nobangela wezi ziphumo zingalindelekanga usasaziwa.Enye into enokwenzeka kukuba imbonakalo yabo eyongeziweyo isenokungabonakalisi uphawu lobushushu begumbi eliphakamileyo, kodwa kunokuba nefuthe elibukhali lokuzisusa ukusuka kwi-30 ° C ukuya kwi-22 ° C ngomhla wokususwa (iimpuku zifumana le mizuzu emi-5-10 ngaphambi kokuba zihambe) .).
Umda jikelele wophononongo lwethu kukuba sifunde iimpuku zamadoda kuphela.Olunye uphando lucebisa ukuba isini sinokuba yingqwalasela ebalulekileyo kwizalathisi zethu eziphambili, njengoko iimpuku zabasetyhini bedolo elinye zibuthathaka ngakumbi ngenxa ye-thermal conductivity ephezulu kunye nokugcina amaqondo obushushu alawulwa ngokungqongqo.Ukongezelela, iigundane zesetyhini (kwi-HFD) zibonise umbutho omkhulu wokuthatha amandla kunye ne-EE kwi-30 ° C xa kuthelekiswa neegundane zamadoda ezidla iigundane ezininzi zesini esifanayo (20 ° C kule meko) 20.Ke, kwiimpuku zabasetyhini, umxholo we-subthermonetral uphezulu, kodwa unepateni efanayo neyeempuku zamadoda.Kuphononongo lwethu, sigxininise kwiimpuku zamadoda anedolo elinye, njengoko ezi ziimeko apho uninzi lwezifundo ze-metabolic ezivavanya i-EE zenziwa.Omnye umda wokufunda kwethu kukuba iimpuku zazikukutya okufanayo kulo lonke uphononongo, oluthintele ukufunda ukubaluleka kweqondo lokushisa kwigumbi lokuguquguquka kwe-metabolic (njengoko kulinganiswe ngotshintsho lwe-RER kwiinguqu zokutya kwiindidi ezahlukeneyo ze-macronutrient).kwiimpuku ezizimazi nezenkunzi ezigcinwe ku-20°C xa kuthelekiswa neempuku ezihambelanayo ezigcinwe kuma-30°C.
Ukuqukumbela, uphononongo lwethu lubonisa ukuba, njengakwezinye izifundo, i-lap 1 yeempuku ezinobunzima obuqhelekileyo zi-thermoneutral ngaphezu kwe-27.5 ° C eqikelelweyo.Ukongezelela, uphando lwethu lubonisa ukuba ukukhuluphala akuyona into enkulu yokukhusela kwiigundane ezinobunzima obuqhelekileyo okanye i-DIO, okubangelwa ukushisa okufanayo: i-EE ratios kwi-DIO kunye neegundane eziqhelekileyo zobunzima.Ngelixa ukutya kweegundane ezinobunzima obuqhelekileyo kwakuhambelana ne-EE kwaye ngaloo ndlela kugcinwe ubunzima bomzimba obuzinzile phezu kweqondo lonke lobushushu, ukutya kweegundane ze-DIO kwakufana namaqondo okushisa ahlukeneyo, okubangelwa umlinganiselo ophezulu weegundane kwi-30 ° C. .kwi-22 ° C ifumene ubunzima bomzimba obuninzi.Lilonke, izifundo ezicwangcisiweyo ezivavanya ukubaluleka okunokubakho kokuphila ngaphantsi kobushushu be-thermoneutral zifanelekile ngenxa yokunganyamezeli kakuhle phakathi kwempuku kunye nezifundo zabantu.Ngokomzekelo, kwizifundo zokukhuluphala, inkcazo yenxalenye yokuguqulela okuhlwempuzekileyo ngokubanzi kunokuba ngenxa yokuba izifundo zokulahlekelwa kwesisindo se-murine zidla ngokuqhutyelwa kwizilwanyana ezixinzelelekileyo ezibandayo ezigcinwe kwindawo yokushisa ngenxa yokwanda kwe-EE.Ukulahlekelwa kwesisindo esigqithisileyo xa kuthelekiswa nobunzima bomzimba obulindelekileyo bomntu, ngokukodwa ukuba indlela yokwenza ixhomekeke ekunyuseni i-EE ngokunyusa umsebenzi we-BAP, osebenzayo ngakumbi kwaye usebenze kwiqondo lokushisa elingaphantsi kwe-30 ° C.
Ngokuhambelana neDanish Animal Experimental Law (1987) kunye neNational Institutes of Health (Ushicilelo No. 85-23) kunye neNgqungquthela yaseYurophu yoKhuseleko lweVertebrate esetyenziselwa uVavanyo kunye nezinye iinjongo zeSayensi (iBhunga leYurophu No. 123, eStrasbourg , 1985).
Iigundane ezingamashumi amabini aneveki ze-C57BL/6J zafunyanwa kwi-Janvier Saint Berthevin Cedex, eFransi, kwaye zanikwa i-ad libitum standard chow (Altromin 1324) kunye namanzi (~22 ° C) emva kweyure ye-12: 12 ukukhanya: umjikelezo omnyama.ubushushu begumbi.Iigundane ze-DIO zamadoda (iiveki ze-20) zifunyenwe kumboneleli ofanayo kwaye zanikwa i-ad libitum ukufikelela kwi-45% yokutya okunamafutha aphezulu (Cat. No. D12451, Research Diet Inc., NJ, USA) kunye namanzi phantsi kweemeko zokukhulisa.Iimpuku zaziqhelaniswe nokusingqongileyo kwiveki phambi kokuqala kophononongo.Kwiintsuku ezimbini ngaphambi kokudluliselwa kwinkqubo ye-calorimetry engathanga ngqo, iigundane zilinganiswe, zixhomekeke kwi-MRI scanning (EchoMRITM, TX, USA) kwaye zahlulwe zibe ngamaqela amane ahambelana nobunzima bomzimba, amanqatha kunye nobunzima bomzimba obuqhelekileyo.
Umzobo womzobo woyilo lophononongo uboniswe kuMfanekiso 8. Iimpuku zaye zatshintshelwa kwinkqubo evaliweyo nelawulwa bubushushu obungathanga ngqo kwi-calorimetry system kwi-Sable Systems Internationals (Nevada, USA), equka izijongi zomgangatho wokutya kunye nomgangatho wamanzi kunye nesakhelo se-Promethion BZ1 esirekhodiweyo. amanqanaba omsebenzi ngokulinganisa izithuba zemiqadi.XYZ.Iigundane (n = 8) zahlaliswa nganye nganye kwi-22, 25, 27.5, okanye i-30 ° C kusetyenziswa ibhedi kodwa akukho ndawo yokuhlala kunye nezinto zokuzalela kwi-12: 12-yure yokukhanya: umjikelo omnyama (ukukhanya: 06: 00- 18: 00) .2500ml/min.Iigundane zaqhelaniswa kwiintsuku ezisi-7 ngaphambi kokubhaliswa.Urekhodisho lwaqokelelwa iintsuku ezine zilandelelana.Emva koko, iigundane zigcinwe kumaqondo okushisa ahlukeneyo kwi-25, 27.5, kunye ne-30 ° C ngeentsuku ezongezelelweyo ze-12, emva koko i-cell concentrates yongezwa njengoko kuchazwe ngezantsi.Okwangoku, amaqela eegundane agcinwe kwi-22 ° C agcinwe kule bushushu iintsuku ezimbini ngaphezulu (ukuqokelela idatha entsha yesiseko), kwaye ke izinga lokushisa landiswa ngamanyathelo e-2 ° C yonke imihla ekuqaleni kwesigaba sokukhanya ( 06:00) de ifike kuma-30 °C Emva koko, iqondo lobushushu lehliswa ukuya kuma-22°C kwaye idatha yaqokelelwa ezinye iintsuku ezimbini.Emva kweentsuku ezimbini ezongezelelweyo zokurekhoda kwi-22 ° C, izikhumba zongezwa kuzo zonke iiseli kuwo onke amaqondo okushisa, kwaye ukuqokelela idatha kwaqala ngosuku lwesibini (usuku lwe-17) kunye neentsuku ezintathu.Emva koko (umhla wama-20), i-nesting material (8-10 g) yongezwa kuzo zonke iiseli ekuqaleni komjikelezo wokukhanya (06:00) kwaye idatha yaqokelelwa ezinye iintsuku ezintathu.Ngaloo ndlela, ekupheleni kophononongo, iigundane ezigcinwe kwi-22 ° C zigcinwe kule bushushu iintsuku ezingama-21/33 kunye ne-22 ° C kwiintsuku ze-8 zokugqibela, ngelixa iigundane kwamanye amaqondo okushisa zigcinwe kule bushushu iintsuku ezingama-33./33 iintsuku.Iimpuku zondliwa ngexesha lokufunda.
Ubunzima obuqhelekileyo kunye neempuku ze-DIO zilandele iinkqubo zophononongo ezifanayo.Ngomhla we-9, iigundane zalinganiswa, i-MRI iskenwa, kwaye yahlulahlulwe yangamaqela anokuthelekiswa nobunzima bomzimba kunye nokwakheka komzimba.Ngomhla we-7, iigundane zidluliselwe kwiqondo lokushisa elivaliweyo elilawulwa yi-calorimetry system engathanga ngqo eyenziwe yi-SABLE Systems International (Nevada, USA).Iimpuku zahlaliswa zodwa zomandlalo kodwa ngaphandle kwendlwana okanye izixhobo zokufihla intloko.Ubushushu bubekwe ku 22, 25, 27.5 okanye 30 °C.Emva kweveki enye ye-acclimatization (iintsuku -7 ukuya kwi-0, izilwanyana azizange ziphazamiseke), idatha yaqokelelwa ngeentsuku ezine ezilandelelanayo (ientsuku ze-0-4, idatha eboniswe kwi-FIGS. 1, 2, 5).Emva koko, iigundane ezigcinwe kwi-25, 27.5 kunye ne-30 ° C zigcinwe phantsi kweemeko eziqhubekayo kude kube yimini ye-17.Ngexesha elifanayo, iqondo lokushisa kwiqela le-22 ° C liye landa ngezikhathi ze-2 ° C yonke imihla ngokulungelelanisa umjikelezo weqondo lokushisa (06: 00 h) ekuqaleni kokuvezwa kokukhanya (idatha iboniswe kwi-Fig. 1) .Ngomhla we-15, ukushisa kwehle ukuya kwi-22 ° C kwaye iintsuku ezimbini zedatha zaqokelelwa ukubonelela ngedatha yesiseko kunyango olulandelayo.Izikhumba zongezwa kuzo zonke iigundane ngosuku lwe-17, kwaye izinto zokuzalela zongezwa ngosuku lwe-20 (umzobo 5).Ngomhla we-23, iigundane zalinganiswa kwaye zaphantsi kwe-MRI scanning, emva koko zashiywa zodwa iiyure ze-24.Ngomhla we-24, iigundane zazizila ngokukhawuleza ukususela ekuqaleni kwe-photoperiod (06: 00) kwaye zafumana i-OGTT (2 g / kg) kwi-12: 00 (i-6-7 iiyure zokuzila ukutya).Emva koko, iimpuku zabuyiselwa kwiimeko zazo ze-SABLE ezifanelekileyo kwaye zabulawa ngosuku lwesibini (usuku lwama-25).
Iigundane ze-DIO (n = 8) zilandele iprotocol efanayo njengeegundane zobunzima obuqhelekileyo (njengoko kuchazwe ngasentla nakwi-Figure 8).Iimpuku zigcine i-45% ye-HFD kulo lonke ulingo lwenkcitho yamandla.
I-VO2 kunye ne-VCO2, kunye noxinzelelo lomphunga wamanzi, zirekhodwe kwi-frequency ye-1 Hz kunye ne-cell time constant ye-2.5 min.Ukutya kunye nokufakwa kwamanzi kwaqokelelwa ngokurekhoda okuqhubekayo (1 Hz) kobunzima bokutya kunye neepayile zamanzi.Umlindi womgangatho osetyenzisiweyo uchaze isisombululo se-0.002 g.Amanqanaba omsebenzi arekhodwa kusetyenziswa i-3D XYZ ye-array monitor, idatha yaqokelelwa kwisisombululo sangaphakathi se-240 Hz kwaye yaxelwa kwisekondi nganye ukulinganisa umgama ohanjiweyo (m) kunye nesisombululo esisebenzayo se-0.25 cm.Idatha yacutshungulwa kunye ne-Sable Systems Macro Interpreter v.2.41, ukubala i-EE kunye ne-RER kunye nokucoca ngaphandle (umzekelo, iziganeko zokutya zobuxoki).Itoliki enkulu iqwalaselwe ukuba ikhuphe idatha yazo zonke iiparamitha rhoqo ngemizuzu emihlanu.
Ukongeza ekulawuleni i-EE, ubushushu be-ambient bunokulawula ezinye iinkalo ze-metabolism, kubandakanywa i-postprandial glucose metabolism, ngokulawula ukukhutshwa kwe-glucose-metabolizing hormones.Ukuvavanya le ngcamango, ekugqibeleni sagqiba isifundo sobushushu bomzimba ngokucaphukisa iigundane ezinobunzima obuqhelekileyo kunye nomthwalo we-glucose womlomo we-DIO (2 g / kg).Iindlela zichazwe ngokweenkcukacha kwizinto ezongezelelweyo.
Ekupheleni kwesifundo (usuku lwe-25), iigundane zazizila ngokukhawuleza kwiiyure ze-2-3 (ukuqala kwi-06: 00), i-anesthetized nge-isoflurane, kwaye ixutywe ngokupheleleyo yi-retroorbital venipuncture.Ubungakanani be-plasma lipids kunye nehomoni kunye neelipids esibindini zichazwe kwiiMathiriyeli ezongezelelweyo.
Ukuphanda ukuba ubushushu beqokobhe bubangela utshintsho lwangaphakathi kwizicubu ze-adipose ezichaphazela i-lipolysis, izicubu ze-inguinal kunye ne-epididymal adipose zakhutshwa ngokuthe ngqo kwiimpuku emva kwenqanaba lokugqibela lokopha.Izicubu zacutshungulwa kusetyenziswa i-ex vivo lipolysis assay esanda kuphuhliswa echazwe kwiiNdlela ezoNgezelelweyo.
I-Brown adipose tissue (BAT) yaqokelelwa ngomhla wokuphela kwesifundo kwaye iqhutywe njengoko kuchazwe kwiindlela ezongezelelweyo.
Idatha inikezelwe njengentsingiselo ± SEM.Iigrafu zenziwe kwiGraphPad Prism 9 (La Jolla, CA) kunye nemizobo yahlelwa kwi-Adobe Illustrator (i-Adobe Systems Incorporated, San Jose, CA).Ukubaluleka kwamanani kwavavanywa kwi-GraphPad Prism kwaye yavavanywa ngovavanyo oludibeneyo lwe-t-test, imilinganiselo ephindaphindiweyo yendlela enye / indlela emibini ye-ANOVA elandelwa luvavanyo lokuthelekisa oluninzi lwe-Tukey, okanye i-ANOVA yendlela enye engasebenziyo elandelwa luvavanyo oluninzi lwe-Tukey lokuthelekisa njengoko kufuneka.Ukuhanjiswa kwe-Gaussian kwedatha kwaqinisekiswa ngovavanyo lwesiqhelo lwe-D'Agostino-Pearson ngaphambi kovavanyo.Ubungakanani besampulu bubonakaliswe kwicandelo elihambelanayo lecandelo elithi "Iziphumo", kunye nakwi-legend.Ukuphindaphinda kuchazwa njengawo nawuphi na umlinganiselo othathwe kwisilwanyana esifanayo (kwi-vivo okanye kwisampuli yezicubu).Ngokubhekiselele kwi-reproducibility yedatha, ukudibanisa phakathi kwenkcitho yamandla kunye nokushisa kwemeko kuboniswe kwizifundo ezine ezizimeleyo zisebenzisa iigundane ezahlukeneyo kunye noyilo olufanayo lokufunda.
Iiprothokholi zovavanyo ezineenkcukacha, izixhobo, kunye nedatha eluhlaza ziyafumaneka ngesicelo esinengqiqo esivela kumbhali okhokelayo uRune E. Kuhre.Olu pho nonongo aluzange luvelise ama-reagents amatsha ahlukileyo, isilwanyana se-transgenic / imigca yeseli, okanye idatha yokulandelelana.
Ukufumana ulwazi oluthe kratya malunga noyilo lwesifundo, bona iNgxelo yoPhando lweNdalo eqhagamshelwe kweli nqaku.
Zonke iinkcukacha zenza igrafu.I-1-7 yafakwa kwindawo yokugcina idatha yeSayensi, inombolo yokungena: 1253.11.sciencedb.02284 okanye https://doi.org/10.57760/sciencedb.02284.Idatha eboniswe kwi-ESM ingathunyelwa kwi-Rune E Kuhre emva kovavanyo olufanelekileyo.
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Fischer, AW, Cannon, B. & Nedergaard, J. Amaqondo obushushu ezindlu afanelekileyo ukuze iimpuku zilinganise indawo yobushushu babantu: Uphononongo lokulinga. Fischer, AW, Cannon, B. & Nedergaard, J. Amaqondo obushushu ezindlu afanelekileyo ukuze iimpuku zilinganise indawo yobushushu babantu: Uphononongo lokulinga.I-Fischer, i-AW, i-Cannon, i-B., kunye ne-Nedergaard, i-J. Ubushushu obufanelekileyo bendlu yeempuku ukulinganisa indawo ye-thermal yomntu: isifundo sokulinga. Fischer, AW, Cannon, B. & Nedergaard, J. 小鼠模拟人类热环境的最佳住房温度：一项实验研究。 Fischer, AW, Cannon, B. & Nedergaard, J.Fisher AW, Cannon B., kunye Nedergaard J. Elona qondo lobushushu lezindlu kwiimpuku ezilinganisa imeko-bume eshushu yomntu: Uphononongo lokulinga.Moore.imetabolism.7, 161-170 (2018).
Keijer, J., Li, M. & Speakman, JR Leliphi elona qondo lobushushu lendlu ukuguqulela imifuniselo yempuku ebantwini? Keijer, J., Li, M. & Speakman, JR Leliphi elona qondo lobushushu lendlu ukuguqulela imifuniselo yempuku ebantwini?UKeyer J, uLee M kunye noSpeakman JR Leliphi elona qondo lobushushu legumbi lokudlulisela imifuniselo yempuku ebantwini? Keijer, J., Li, M. & Speakman, JR 将小鼠实验转化為人类的最佳外壳度是多少? Keijer, J., Li, M. & Speakman, JRU-Keyer J, u-Lee M kunye no-Speakman JR Leliphi elona qondo lobushushu leqokobhe lokudlulisela imifuniselo yempuku ebantwini?Moore.imetabolism.25, 168-176 (2019).
Seeley, RJ & MacDougald, OA Iimpuku njengemifuziselo yovavanyo lwefiziyoloji yomntu: xa iidigri ezininzi kumcimbi wobushushu bezindlu. Seeley, RJ & MacDougald, OA Iimpuku njengemifuziselo yovavanyo lwefiziyoloji yomntu: xa iidigri ezininzi kumcimbi wobushushu bezindlu. Seeley, RJ & MacDougald, OA Мыши как экспериментальные модели для физиологии человека: когда несколько градусов в жилище имеют значение. Seeley, RJ & MacDougald, OA Iimpuku njengemizekelo yovavanyo lwe-physiology yabantu: xa iidigri ezimbalwa kwindawo yokuhlala zenza umahluko. Seeley, RJ & MacDougald, OA 小鼠作為人类生理学的实验模型：当几度的住房温度很重要时. Seeley, RJ & MacDougald, OA Мыши Seeley, RJ & MacDougald, OA как экспериментальная модель физиологии человека: когда несколько градусов температуры в помеении человека Seeley, RJ & MacDougald, OA iimpuku njengemodeli yokulinga ye-physiology yabantu: xa iidigri ezimbalwa zobushushu begumbi zibalulekile.Imetabolism yesizwe.3, 443–445 (2021).
Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo kumbuzo othi "Yintoni elona qondo lokushisa lezindlu ukuguqulela iimvavanyo zemouse ebantwini?" Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo kumbuzo othi "Yintoni elona qondo lokushisa lezindlu ukuguqulela iimvavanyo zemouse ebantwini?" Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo kumbuzo othi "Leliphi iqondo lokushisa elingcono kakhulu lokudlulisa iimvavanyo zemouse ebantwini?" Fischer, AW, Cannon, B. & Nedergaard, J. 问题的答案“将小鼠实验转化为人类的最佳外壳温度是多少? Fischer, AW, Cannon, B. & Nedergaard, J.UFisher AW, uCannon B., kunye noNedergaard J. Iimpendulo kumbuzo othi "Leliphi iqokobhe elilelona lobushushu lokudlulisela imifuniselo yempuku ebantwini?"Ewe: thermoneutral.Moore.imetabolism.26, 1-3 (2019).
Ixesha lokuposa: Oct-28-2022
