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Izifundo eziningi ze-metabolic kumagundane zenziwa ekamelweni lokushisa, nakuba ngaphansi kwalezi zimo, ngokungafani nabantu, amagundane achitha amandla amaningi egcina izinga lokushisa langaphakathi.Lapha, sichaza isisindo esivamile kanye nokukhuluphala okubangelwa ukudla (DIO) ku-C57BL/6J amagundane adliwe i-chow chow noma ukudla okunamafutha aphezulu angu-45%, ngokulandelana.Amagundane abekwe izinsuku ezingu-33 ku-22, 25, 27.5 kanye no-30 ° C. ohlelweni lwe-calorimetry olungaqondile.Sibonisa ukuthi izindleko zamandla zenyuka ngokomugqa zisuka ku-30°C ziye ku-22°C futhi cishe ziphakeme ngo-30% ngo-22°C kuwo womabili amamodeli wamagundane.Emagundaneni anesisindo esijwayelekile, ukudla kuphambane ne-EE.Ngokuphambene, amagundane e-DIO awazange anciphise ukudla lapho i-EE yehla.Ngakho, ekupheleni kocwaningo, amagundane ku-30 ° C ayenesisindo somzimba esiphezulu, isisindo samafutha kanye ne-plasma glycerol kanye ne-triglycerides kunamagundane ku-22 ° C.Ukungalingani kumagundane e-DIO kungase kube ngenxa yokwanda kokudla okusekelwe enjabulweni.
Igundane liyimodeli yezilwane esetshenziswa kakhulu ocwaningweni lwesayensi yokwakheka komzimba womuntu kanye ne-pathophysiology, futhi ngokuvamile iyisilwane esizenzakalelayo esisetshenziswa ezigabeni zokuqala zokutholwa nokuthuthukiswa kwezidakamizwa.Kodwa-ke, amagundane ahluka kubantu ngezindlela ezimbalwa ezibalulekile zomzimba, futhi ngenkathi ukukala kwe-allometric kungasetshenziswa ngokwezinga elithile ukuze kuhunyushelwe kubantu, umehluko omkhulu phakathi kwamagundane nabantu ulele ku-thermoregulation kanye ne-homeostasis yamandla.Lokhu kubonisa ukungqubuzana okuyisisekelo.Isilinganiso somzimba wamagundane amadala okungenani singaphansi ngokuphindwe ngenkulungwane kunesabantu abadala (50 g vs. 50 kg), futhi indawo engaphezulu kuya kobukhulu ihluka izikhathi ezingaba ngu-400 ngenxa yoguquko lwejiyomethri olungaqondile oluchazwe ngu-Mee. .Isibalo sesi-2. Ngenxa yalokho, amagundane alahlekelwa ukushisa okwengeziwe ngokuphawulekayo okuhlobene nevolumu yawo, ngakho azwela kakhulu izinga lokushisa, athambekele kakhulu ku-hypothermia, futhi anesilinganiso se-basal metabolic rate esiphindwe kashumi ngaphezu kwesabantu.Ezingeni lokushisa elijwayelekile legumbi (~22°C), amagundane kufanele akhuphule inani lawo lezindleko zamandla (EE) cishe ngo-30% ukuze agcine izinga lokushisa lomzimba eliyisisekelo.Emazingeni okushisa aphansi, i-EE ikhuphuka nakakhulu cishe ngo-50% no-100% ku-15 no-7°C uma kuqhathaniswa ne-EE ku-22°C.Ngakho-ke, izimo zezindlu ezijwayelekile zenza impendulo yokucindezeleka ebandayo, engase ibeke engozini ukudluliswa kwemiphumela yegundane kubantu, njengoba abantu abahlala emiphakathini yesimanje bechitha isikhathi sabo esiningi ezimweni ze-thermoneutral (ngoba indawo yethu ephansi yesilinganiso ingaphezulu kuya kwivolumu isenza singazweli kakhulu izinga lokushisa, njengoba sakha indawo ye-thermoneutral (TNZ) esizungezile. I-EE ngaphezu kwesilinganiso se-basal metabolic) idlula ~19 kuya ku-30°C6, kuyilapho amagundane anebhande eliphakeme nelincane elihlanganisa kuphela u-2–4°C7,8 Eqinisweni, lokhu okubalulekile isici sithole ukunakwa okukhulu eminyakeni yamuva4, 7,8,9,10,11,12 futhi kuye kwaphakanyiswa ukuthi okunye “ukwahlukana kwezinhlobo” kungancishiswa ngokukhuphula izinga lokushisa legobolondo 9. Nokho, akukho ukuvumelana ngebanga lokushisa lokho kwenza i-thermoneutrality kumagundane.Ngakho-ke, kungakhathaliseki ukuthi izinga lokushisa eliphansi elibucayi ebangeni le-thermoneutral kumagundane edolo elilodwa liseduze no-25 ° C noma eduze no-30 ° C4, 7, 8, 10, 12 lihlala liphikisana.I-EE namanye amapharamitha we-metabolic akhawulelwe emahoreni kuya ezinsukwini, ngakho-ke izinga lapho ukuchayeka isikhathi eside kumazinga okushisa ahlukene kungathinta imingcele ye-metabolic njengesisindo somzimba akucaci.ukusetshenziswa, ukusetshenziswa kwe-substrate, ukubekezelelana kwe-glucose, kanye nokugxila kwe-plasma lipid kanye ne-glucose nama-hormone alawula ukudla.Ukwengeza, ucwaningo olwengeziwe luyadingeka ukuze kutholwe ukuthi izinga lokudla lingathonya kangakanani le mingcele (amagundane e-DIO ekudleni okunamafutha amaningi angase aqondiswe kakhulu ekudleni okusekelwe enjabulweni (hedonic).Ukuze sinikeze ulwazi olwengeziwe ngalesi sihloko, sihlole umphumela wokukhulisa izinga lokushisa kumapharamitha we-metabolic ashiwo ngenhla kumagundane amaduna amadala anesisindo esijwayelekile kanye namagundane abesilisa abangelwa ukudla (DIO) ekudleni okunamafutha aphezulu angu-45%.Amagundane agcinwa ku-22, 25, 27.5, noma 30 ° C okungenani amasonto amathathu.Amazinga okushisa angaphansi kuka-22°C awahlolisiswanga ngoba indawo yokuhlala yezilwane akuvamile ukuba ibe ngaphansi kwezinga lokushisa legumbi.Sithole ukuthi amagundane e-DIO anesisindo esivamile kanye nendingilizi eyodwa aphendule ngendlela efanayo ezinguqukweni zezinga lokushisa lendawo ebiyelwe ngokuya nge-EE futhi kungakhathaliseki isimo sokuvaleleka (okunendawo yokuhlala noma ngaphandle kwayo).Kodwa-ke, ngenkathi amagundane esisindo esijwayelekile elungisa ukudla kwawo ngokwe-EE, ukudla kwamagundane e-DIO kwakuzimele kakhulu ku-EE, okuholele ekutheni amagundane athole isisindo esengeziwe.Ngokusho kwedatha yesisindo somzimba, ukugxiliswa kwe-plasma kwe-lipids nemizimba ye-ketone kubonise ukuthi amagundane e-DIO ku-30 ° C abe nebhalansi yamandla enhle kakhulu kunamagundane ku-22 ° C.Izizathu eziyisisekelo zomehluko ekulinganiseni kokuthatha amandla kanye ne-EE phakathi kwesisindo esijwayelekile namagundane e-DIO zidinga ukufundwa okwengeziwe, kodwa zingase zihlobane nezinguquko ze-pathophysiological kumagundane e-DIO kanye nomthelela wokudla okusekelwe enjabulweni njengomphumela wokukhuluphala ngokweqile.
I-EE inyuke ngokomugqa isuka ku-30 iye ku-22°C futhi yayicishe ibe ngu-30% ephakeme ngo-22°C uma kuqhathaniswa no-30°C (Fig. 1a,b).Izinga lokushintshana kokuphefumula (RER) lalizimele ezingeni lokushisa (Fig. 1c, d).Ukudla kwakuhambisana nokuguquguquka kwe-EE futhi kukhuphuke ngezinga lokushisa elinciphayo (futhi ~30% ngaphezu kuka-22°C uma kuqhathaniswa no-30°C (Fig. 1e,f). Ukuthathwa kwamanzi.Ivolumu kanye nezinga lomsebenzi akuzange kuncike ezingeni lokushisa (Fig. 1g).
Amagundane abesilisa (i-C57BL / 6J, amasonto angu-20 ubudala, izindlu zomuntu ngamunye, n = 7) afakwe emakhejini e-metabolic ku-22 ° C. isonto elilodwa ngaphambi kokuqala kocwaningo.Ezinsukwini ezimbili ngemva kokuqoqwa kwedatha yangasemuva, izinga lokushisa lanyuswa ngokunyuka okungu-2°C ngo-06:00 amahora ngosuku (ukuqala kwesigaba sokukhanya).Idatha yethulwa njengephutha ± elijwayelekile lencazelo, futhi isigaba esimnyama (18:00–06:00 h) simelelwa ibhokisi elimpunga.a Izindleko zamandla (kcal/h), b Isamba sezindleko zamandla emazingeni okushisa ahlukahlukene (kcal/24 h), c Izinga lokushintshanisa lokuphefumula (VCO2/VO2: 0.7–1.0), d Kusho i-RER ekukhanyeni nasekumnyama (VCO2 /VO2) isigaba (inani elinguziro lichazwa ngokuthi 0.7).e ukunqwabelana kokudla (g), f 24h isamba sokudla, g 24h isiyonke amanzi athathwayo (ml), h 24h isiyonke amanzi athathwayo, i izinga lomsebenzi okhulayo (m) kanye j isamba sezinga lomsebenzi (m/24h) .).Amagundane agcinwa ezingeni lokushisa elibonisiwe amahora angama-48.Idatha ekhonjiswe ku-24, 26, 28 kanye no-30°C ibhekisela emahoreni angu-24 okugcina omjikelezo ngamunye.Amagundane ahlala ondlekile ngesikhathi socwaningo.Ukubaluleka kwezibalo kuhlolwe izilinganiso eziphindaphindiwe ze-ANOVA yendlela eyodwa kulandele ukuhlolwa kokuqhathanisa okuningi kuka-Tukey.Izinkanyezi zibonisa ukubaluleka kwevelu yokuqala engu-22°C, ukufiphaza kubonisa ukubaluleka phakathi kwamanye amaqembu njengoba kukhonjisiwe. *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.Amanani amaphakathi abalwe kuso sonke isikhathi sokuhlola (amahora angu-0-192).n = 7.
Njengoba endabeni yamagundane esisindo esivamile, i-EE yanda ngokulinganayo ngokunciphisa izinga lokushisa, futhi kulokhu, i-EE nayo yayicishe ibe ngu-30% ephakeme ku-22 ° C uma kuqhathaniswa no-30 ° C (Fig. 2a,b).I-RER ayizange ishintshe emazingeni okushisa ahlukene (Fig. 2c, d).Ngokuphambene namagundane esisindo esivamile, ukudla kwakungahambelani ne-EE njengomsebenzi wezinga lokushisa legumbi.Ukudla okudlayo, ukuthathwa kwamanzi, kanye nezinga lomsebenzi kwakungamele izinga lokushisa (Fig. 2e–j).
Owesilisa (C57BL/6J, amaviki angu-20) amagundane e-DIO ahlaliswa ngawodwana emakhejini e-metabolic ku-22° C. isonto elilodwa ngaphambi kokuqala kocwaningo.Amagundane angasebenzisa u-45% we-HFD ad libitum.Ngemuva kokujwayela izinsuku ezimbili, idatha yesisekelo yaqoqwa.Ngemva kwalokho, izinga lokushisa lalikhushulwa ngokunyuka okungu-2°C njalo ngolunye usuku ngo-06:00 (ukuqala kwesigaba sokukhanya).Idatha yethulwa njengephutha ± elijwayelekile lencazelo, futhi isigaba esimnyama (18:00–06:00 h) simelelwa ibhokisi elimpunga.a Izindleko zamandla (kcal/h), b Isamba sezindleko zamandla emazingeni okushisa ahlukahlukene (kcal/24 h), c Izinga lokushintshanisa lokuphefumula (VCO2/VO2: 0.7–1.0), d Kusho i-RER ekukhanyeni nasekumnyama (VCO2 /VO2) isigaba (inani elinguziro lichazwa ngokuthi 0.7).e ukunqwabelana kokudla (g), f 24h isamba sokudla, g 24h isiyonke amanzi athathwayo (ml), h 24h isiyonke amanzi athathwayo, i izinga lomsebenzi okhulayo (m) kanye j isamba sezinga lomsebenzi (m/24h) .).Amagundane agcinwa ezingeni lokushisa elibonisiwe amahora angama-48.Idatha ekhonjiswe ku-24, 26, 28 kanye no-30°C ibhekisela emahoreni angu-24 okugcina omjikelezo ngamunye.Amagundane agcinwe ku-45% HFD kuze kube sekupheleni kocwaningo.Ukubaluleka kwezibalo kuhlolwe izilinganiso eziphindaphindiwe ze-ANOVA yendlela eyodwa kulandele ukuhlolwa kokuqhathanisa okuningi kuka-Tukey.Izinkanyezi zibonisa ukubaluleka kwevelu yokuqala engu-22°C, ukufiphaza kubonisa ukubaluleka phakathi kwamanye amaqembu njengoba kukhonjisiwe. *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.Amanani amaphakathi abalwe kuso sonke isikhathi sokuhlola (amahora angu-0-192).n = 7.
Kolunye uchungechunge lokuhlola, sihlole umthelela wezinga lokushisa le-ambient kumapharamitha afanayo, kodwa kulokhu phakathi kwamaqembu amagundane ayehlala egcinwe ezingeni elithile lokushisa.Amagundane ahlukaniswe ngamaqembu amane ukuze kuncishiswe izinguquko zezibalo ekuphambukeni okulinganiselwe kanye nokujwayelekile kwesisindo somzimba, amafutha, nesisindo somzimba esivamile (Fig. 3a-c).Ngemva kwezinsuku ezingu-7 zokujwayela, izinsuku ezingu-4.5 ze-EE zarekhodwa.I-EE ithinteka kakhulu ekushiseni kwe-ambient kokubili phakathi namahora okukhanya kwasemini nasebusuku (Fig. 3d), futhi inyuka ngokulandelana njengoba izinga lokushisa lincipha kusuka ku-27.5 ° C kuya ku-22 ° C (Fig. 3e).Uma kuqhathaniswa namanye amaqembu, i-RER yeqembu le-25 ° C yancishiswa ngandlela-thile, futhi kwakungekho umehluko phakathi kwamaqembu asele (Fig. 3f, g).Ukudla okuhambisana nephethini ye-EE kukhuphuke cishe ngo-30% ku-22°C uma kuqhathaniswa no-30°C (Fig. 3h,i).Ukusetshenziswa kwamanzi kanye namazinga omsebenzi awazange ahluke kakhulu phakathi kwamaqembu (Fig. 3j,k).Ukuchayeka emazingeni okushisa ahlukene kuze kufike ezinsukwini ezingama-33 akuzange kuholele ekuhlukeni kwesisindo somzimba, isisindo esinciphile, nesisindo samafutha phakathi kwamaqembu (Fig. 3n-s), kodwa kubangele ukwehla kwesisindo somzimba omncane cishe ngo-15% uma kuqhathaniswa izikolo ezizibikayo (Fig. 3n-s).3b, r, c)) kanye nesisindo samafutha sanda izikhathi ezingaphezu kwezingu-2 (kusuka ~ ~ 1 g kuya ku-2-3 g, Fig. 3c, t, c).Ngeshwa, ikhabhinethi engu-30°C inamaphutha okulinganisa futhi ayikwazi ukunikeza idatha enembile ye-EE ne-RER.
- Isisindo somzimba (a), isisindo somzimba omncane (b) namafutha (c) ngemva kwezinsuku eziyi-8 (usuku olulodwa ngaphambi kokudluliselwa ohlelweni lwe-SABLE).d Ukusetshenziswa kwamandla (kcal/h).e Isilinganiso sokusetshenziswa kwamandla (amahora angu-0–108) emazingeni okushisa ahlukahlukene (kcal/amahora angu-24).f Isilinganiso sokushintshanisa ukuphefumula (RER) (VCO2/VO2).g Kusho i-RER (VCO2/VO2).h Isamba sokudla esikudlayo (g).i Kusho ukudla okudlayo (g/amahora angama-24).j Isamba esisetshenziswa amanzi (ml).k Isilinganiso sokusetshenziswa kwamanzi (ml/24 h).l Izinga lomsebenzi oqoqwayo (m).m Isilinganiso sezinga lomsebenzi (m/24 h).Isisindo somzimba ngosuku lwe-18, o ukushintsha kwesisindo somzimba (kusuka -8 kuya osukwini lwe-18), isisindo esithambile ngosuku lwe-18, q ukuguquka kwesisindo somzimba (kusuka -8th kuya osukwini lwe-18), r isisindo samafutha ngosuku lwe-18 , kanye nokushintsha kwesisindo samafutha (kusuka -8 kuya ezinsukwini ezingu-18).Ukubaluleka kwezibalo kwezinyathelo eziphindaphindiwe kuhlolwe yi-Oneway-ANOVA kulandelwa ukuhlolwa okuningi kokuqhathanisa kuka-Tukey. *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 yethulwa njengephutha + elivamile lencazelo, isigaba esimnyama (18:00-06:00 h) simelelwa amabhokisi ampunga.Amachashazi kuma-histograms amele amagundane ngamanye.Amanani amaphakathi abalwe kuso sonke isikhathi sokuhlola (amahora angu-0-108).n = 7.
Amagundane afaniswa ngesisindo somzimba, isisindo esincane, kanye nesisindo samafutha ekuqaleni (Amakhiwane 4a-c) futhi agcinwe ku-22, 25, 27.5, kanye ne-30 ° C njengezifundo ezinamagundane esisindo esivamile..Uma kuqhathaniswa amaqembu amagundane, ubudlelwano phakathi kwe-EE nezinga lokushisa bubonise ubudlelwano bomugqa obufanayo nezinga lokushisa ngokuhamba kwesikhathi kumagundane afanayo.Ngakho-ke, amagundane agcinwe ku-22 ° C adla amandla angaba ngu-30% ngaphezu kwamagundane agcinwe ku-30 ° C (Fig. 4d, e).Lapho kufundwa imiphumela ezilwaneni, izinga lokushisa alizange lihlale lithinta i-RER (Fig. 4f,g).Ukudla, ukungenisa kwamanzi, kanye nomsebenzi akuzange kuthinteke kakhulu izinga lokushisa (Fig. 4h–m).Ngemva kwezinsuku ezingu-33 zokukhuliswa, amagundane ku-30 ° C ayenesisindo somzimba esiphezulu kakhulu kunamagundane ku-22 ° C (Fig. 4n).Uma kuqhathaniswa namaphuzu awo ayisisekelo ahlukene, amagundane akhuliswe ku-30°C ayenesisindo somzimba esiphakeme kakhulu kunamagundane akhuliswe ngo-22°C (kusho iphutha ± elijwayelekile lencazelo: Fig. 4o).Ukuzuza kwesisindo esiphakeme kakhulu kwakungenxa yokwanda kwesisindo samafutha (Fig. 4p, q) kunokuba ukwanda kwesisindo esincane (Fig. 4r, s).Ngokuhambisana nenani eliphansi le-EE ku-30°C, ukuvezwa kwezakhi zofuzo ezimbalwa ze-BAT ezikhuphula umsebenzi/umsebenzi we-BAT kwehliswe ku-30°C uma kuqhathaniswa no-22°C: Adra1a, Adrb3, kanye ne-Prdm16.Ezinye izakhi zofuzo eziyisihluthulelo ezibuye zikhulise umsebenzi/umsebenzi we-BAT azizange zithinteke: I-Sema3a (ukulawulwa kokukhula kwe-neurite), i-Tfam (i-mitochondrial biogenesis), i-Adrb1, i-Adra2a, i-Pck1 (igluconeogenesis) ne-Cpt1a.Ngokumangalisayo, i-Ucp1 ne-Vegf-a, ehlotshaniswa nokwanda komsebenzi we-thermogenic, ayizange yehle eqenjini le-30 ° C.Eqinisweni, amazinga e-Ucp1 kumagundane amathathu ayephakeme kuneqembu le-22 ° C, futhi i-Vegf-a ne-Adrb2 yayiphakeme kakhulu.Uma kuqhathaniswa neqembu le-22 °C, amagundane agcinwe ku-25 °C no-27.5 °C abonisanga ushintsho (Umfanekiso Owengeziwe 1).
- Isisindo somzimba (a), isisindo somzimba omncane (b) namafutha (c) ngemva kwezinsuku eziyi-9 (usuku olulodwa ngaphambi kokudluliselwa ohlelweni lwe-SABLE).d Ukusetshenziswa kwamandla (EE, kcal/h).e Isilinganiso sokusetshenziswa kwamandla (0-96 amahora) emazingeni okushisa ahlukahlukene (kcal/amahora angama-24).f Isilinganiso sokushintshanisa ukuphefumula (RER, VCO2/VO2).g Kusho i-RER (VCO2/VO2).h Isamba sokudla esikudlayo (g).i Kusho ukudla okudlayo (g/amahora angama-24).j Isamba esisetshenziswa amanzi (ml).k Isilinganiso sokusetshenziswa kwamanzi (ml/24 h).l Izinga lomsebenzi oqoqwayo (m).m Isilinganiso sezinga lomsebenzi (m/24 h).n Isisindo somzimba ngosuku 23 (g), o Ukushintsha kwesisindo somzimba, p Isisindo esincane, q Ukushintsha kwesisindo somzimba (g) ngosuku lwama-23 uma kuqhathaniswa nosuku lwesi-9, Ukushintsha kwesisindo (g) ku-23 -day, amafutha isisindo (g) uma kuqhathaniswa nosuku lwesi-8, usuku lwama-23 uma kuqhathaniswa nosuku lwesi-8.Ukubaluleka kwezibalo kwezinyathelo eziphindaphindiwe kuhlolwe yi-Oneway-ANOVA kulandelwa ukuhlolwa okuningi kokuqhathanisa kuka-Tukey. *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 yethulwa njengephutha + elivamile lencazelo, isigaba esimnyama (18:00-06:00 h) simelelwa amabhokisi ampunga.Amachashazi kuma-histograms amele amagundane ngamanye.Amanani amaphakathi abalwe kuso sonke isikhathi sokuhlola (amahora angu-0-96).n = 7.
Njengabantu, amagundane avame ukudala i-microenvironment ukunciphisa ukulahlekelwa ukushisa endaweni.Ukuze silinganise ukubaluleka kwale ndawo ku-EE, sihlole i-EE kokungu-22, 25, 27.5, kanye no-30°C, ngonogada besikhumba noma ngaphandle kwezinto zokuzalela.Ku-22°C, ukungezwa kwezikhumba ezijwayelekile kunciphisa i-EE cishe ngo-4%.Ukwengezwa okulandelayo kwezinto zokuzalela kwehlise i-EE ngo-3–4% (Fig. 5a,b).Azikho izinguquko eziphawulekayo ku-RER, ukuthathwa kokudla, ukuthathwa kwamanzi, noma amazinga omsebenzi abonwa ngokungezwa kwezindlu noma izikhumba + zokulala (Umfanekiso 5i–p).Ukwengezwa kwesikhumba nezinto zokuzalela kuphinde kwehlise kakhulu i-EE ku-25 no-30°C, kodwa izimpendulo bezizincane ngobuningi.Ku-27.5°C akukho mehluko obonwe.Ngokuphawulekayo, kulezi zivivinyo, i-EE yehla ngezinga lokushisa elikhulayo, kulokhu cishe i-57% ephansi kune-EE ku-30 ° C uma kuqhathaniswa no-22 ° C (Fig. 5c-h).Ukuhlaziywa okufanayo kwenziwa kuphela esigabeni sokukhanya, lapho i-EE yayisondelene nesilinganiso se-basal metabolic, njengoba kulokhu amagundane ayehlala esikhumbeni, okuholela kumasayizi omphumela ofanayo emazingeni okushisa ahlukene (I-Supplementary Fig. 2a–h) .
Idatha yamagundane avela endaweni yokukhosela nezinto zokuzalela (okuluhlaza okwesibhakabhaka okumnyama), ikhaya kodwa okungekho okuzalelayo (okuluhlaza okwesibhakabhaka okukhanyayo), kanye nokokusebenza kwekhaya nesidleke (okuwolintshi).Ukusetshenziswa kwamandla (EE, kcal/h) kumakamelo a, c, e no-g ku-22, 25, 27.5 no-30 °C, b, d, f kanye no-h kusho i-EE (kcal/h).ip Idatha yamagundane agcinwe ku-22°C: i isilinganiso sokuphefumula (RER, VCO2/VO2), j kusho i-RER (VCO2/VO2), k ukudla okuhlanganisiwe (g), l isilinganiso sokudla (g/24 h), m inani lamanzi asetshenzisiwe (mL), n isilinganiso samanzi sokudla i-AUC (mL/24h), o isiyonke umsebenzi (m), p isilinganiso sezinga lomsebenzi (m/24h).Idatha yethulwa njengephutha + elivamile lencazelo, isigaba esimnyama (18:00-06:00 h) simelelwa amabhokisi ampunga.Amachashazi kuma-histograms amele amagundane ngamanye.Ukubaluleka kwezibalo kwezinyathelo eziphindaphindiwe kuhlolwe yi-Oneway-ANOVA kulandelwa ukuhlolwa okuningi kokuqhathanisa kuka-Tukey. *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.Amanani amaphakathi abalwe kuso sonke isikhathi sokuhlola (amahora angu-0-72).n = 7.
Emagundaneni esisindo esivamile (amahora angu-2-3 wokuzila ukudla), ukukhuliswa emazingeni okushisa ahlukene akuzange kubangele umehluko omkhulu ekugxilweni kwe-plasma ye-TG, 3-HB, i-cholesterol, i-ALT, ne-AST, kodwa i-HDL njengomsebenzi wokushisa.Umfanekiso 6a-e).Ukugxila kwe-plasma okuzila ukudla kwe-leptin, i-insulin, i-C-peptide, ne-glucagon nakho akuzange kuhluke phakathi kwamaqembu (Izibalo 6g-j).Ngosuku lokuhlolwa kokubekezelela i-glucose (ngemuva kwezinsuku ezingama-31 emazingeni okushisa ahlukene), izinga le-glucose eyisisekelo (amahora angama-5-6 wokuzila ukudla) lalicishe libe ngu-6.5 mM, kungekho mehluko phakathi kwamaqembu. Ukuphathwa kwe-glucose yomlomo kukhuphule ukugxila kweglucose yegazi kakhulu kuwo wonke amaqembu, kepha kokubili ukugxila okuphezulu kanye nendawo ekhuphukayo ngaphansi kwamajika (iAUCs) (i-15-120 min) yayiphansi eqenjini lamagundane agcinwe ku-30 ° C (amaphuzu esikhathi ngasinye: P < 0.05–P < 0.0001, Fig. 6k, l) uma kuqhathaniswa namagundane agcinwe ku-22, 25 kanye no-27.5 °C (okungazange kuhluke phakathi kwelinye). Ukuphathwa kwe-glucose yomlomo kukhuphule ukugxila kweglucose yegazi kakhulu kuwo wonke amaqembu, kepha kokubili ukugxila okuphezulu kanye nendawo ekhuphukayo ngaphansi kwamajika (iAUCs) (i-15-120 min) yayiphansi eqenjini lamagundane agcinwe ku-30 ° C (amaphuzu esikhathi ngasinye: P < 0.05–P < 0.0001, Fig. 6k, l) uma kuqhathaniswa namagundane agcinwe ku-22, 25 kanye no-27.5 °C (okungahlukanga phakathi kwamanye). Пероральное введение глюкозы значительно повышало концентрацию глюкозы в крови во всех группах, но как пиковая концентрация, так и площадь приращения под кривыми (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 kanye 27,5 ° C (которые не различались межобе собег). Ukuphathwa ngomlomo kwe-glucose kwandise kakhulu ukugxila kwe-glucose yegazi kuwo wonke amaqembu, kodwa kokubili ukugxila okuphezulu kanye nendawo ekhuphukayo ngaphansi kwamajika (i-iAUC) (i-15-120 min) yayiphansi eqenjini lamagundane angu-30 ° C (izikhathi ezihlukene: P <0.05- P <0.0001, Fig. 6k, l) uma kuqhathaniswa namagundane agcinwe ku-22, 25 no-27.5 °C (okungahlukanga komunye nomunye).口服 葡萄糖 的 给 药药:P <0.05–P <0.0001,图6k,l）与饲养在22,25 and27.5°C 的小鼠（彼此之间有差异）相比。口服 葡萄糖 的 给给 药 了 所有组 血糖 浓度 但 在 在 在 饲养 小 小 鼠组 中, 浓度浓度Umthamo:P <0.05–P <0.0001,图6k,l）与饲养在22,25和27.5°C 的小鼠Ukuphathwa ngomlomo kwe-glucose kwandisa kakhulu ukugxila kweglucose yegazi kuwo wonke amaqembu, kodwa kokubili ukugxila okuphezulu kanye nendawo engaphansi kwejika (i-iAUC) (i-15-120 min) yayiphansi eqenjini lamagundane e-30 ° C-feed (zonke izikhathi).: P <0,05–P <0,0001, рис. : P <0.05–P <0.0001, Fig.6l, l) uma kuqhathaniswa namagundane agcinwe ku-22, 25 kanye no-27.5 ° C (akukho mehluko komunye nomunye).
Ukugxiliswa kwe-plasma kwe-TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulini, C-peptide, neglucagon kuboniswa kumagundane abesilisa asebekhulile i-DIO(al) ngemva kwezinsuku ezingu-33 zokudla ezingeni lokushisa elibonisiwe. .Amagundane awazange anikezwe amahora angama-2-3 ngaphambi kokuthatha isampula yegazi.Okuhlukile kwakuwukuhlolwa kokubekezelela i-glucose ngomlomo, okwenziwa ezinsukwini ezimbili ngaphambi kokuphela kocwaningo kumagundane azila ukudla amahora angama-5-6 futhi agcinwa ezingeni lokushisa elifanele izinsuku ezingama-31.Amagundane abekwe inselele ngesisindo somzimba esingu-2 g/kg.Indawo engaphansi kwedatha yejika (L) ivezwa njengedatha ekhuphukayo (iAUC).Idatha yethulwa njengencazelo ± SEM.Amachashazi amelela amasampula ngamanye. *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.
Kumagundane e-DIO (futhi azila ukudla amahora angu-2-3), i-cholesterol ye-plasma, i-HDL, i-ALT, i-AST, ne-FFA yokugxila ayizange ihluke phakathi kwamaqembu.Kokubili i-TG ne-glycerol kwakuphakeme kakhulu eqenjini le-30 ° C uma kuqhathaniswa neqembu le-22 ° C (Izibalo 7a-h).Ngokuphambene, i-3-GB yayicishe ibe ngu-25% ngaphansi ku-30°C uma iqhathaniswa no-22°C (Umfanekiso 7b).Ngakho-ke, nakuba amagundane agcinwe ku-22 ° C ayenokulinganisela kwamandla okuhle, njengoba kuphakanyiswe ukuzuza kwesisindo, umehluko ekugxilweni kwe-plasma ye-TG, glycerol, ne-3-HB iphakamisa ukuthi amagundane ku-22 ° C lapho isampula yayingaphansi kuka-22 °. C.°C.Amagundane akhuliswe ku-30 °C abesesimweni esibi ngokuqhathaniswa namandla.Ngokuvumelana nalokhu, ukugxila kwesibindi se-glycerol ne-TG, kodwa hhayi i-glycogen ne-cholesterol, kwakuphezulu eqenjini le-30 ° C (I-Supplementary Fig. 3a-d).Ukuze siphenye ukuthi ingabe umehluko oncike kuzinga lokushisa ku-lipolysis (njengoba kukalwa nge-plasma TG ne-glycerol) ungumphumela woshintsho lwangaphakathi kumafutha e-epididymal noma e-inguinal, sikhiphe izicubu ze-adipose kulezi zitolo ekupheleni kocwaningo futhi salinganisa inani le-acid yamahhala yamahhala. vivo.kanye nokukhululwa kwe-glycerol.Kuwo wonke amaqembu okuhlola, amasampula ezicubu ze-adipose avela kumadepho e-epididymal kanye ne-inguinal abonise okungenani ukwanda okuphindwe kabili kokukhiqizwa kwe-glycerol ne-FFA ekuphenduleni ukukhuthazwa kwe-isoproterenol (I-Supplementary Fig. 4a-d).Kodwa-ke, akukho mphumela wokushisa kwegobolondo ku-basal noma i-isoproterenol-stimulated lipolysis etholakele.Ngokuhambisana nesisindo somzimba esiphezulu kanye nesisindo samafutha, amazinga e-plasma leptin ayephezulu kakhulu eqenjini le-30 ° C kuneqembu le-22 ° C (Umfanekiso 7i).Ngokuphambene nalokho, amazinga e-plasma e-insulin ne-C-peptide awazange ahluke phakathi kwamaqembu okushisa (Fig. 7k, k), kodwa i-plasma glucagon ibonise ukuncika ekushiseni, kodwa kulokhu cishe i-22 ° C eqenjini eliphambene laliqhathaniswa kabili. kuya ku-30°C.KUSUKA.Iqembu C (Fig. 7l).I-FGF21 ayizange ihluke phakathi kwamaqembu okushisa ahlukene (Fig. 7m).Ngosuku lwe-OGTT, i-glucose eyisisekelo yegazi yayicishe ibe ngu-10 mM futhi ayizange ihluke phakathi kwamagundane agcinwe emazingeni okushisa ahlukene (Fig. 7n).Ukuphathwa ngomlomo kwe-glucose kwenyusa amazinga kashukela egazini futhi kwenyuke kuwo wonke amaqembu ekuhlanganisweni okungaba ngu-18 mM emizuzwini eyi-15 ngemuva komthamo.Kwakungekho mehluko obalulekile ku-iAUC (i-15-120 min) kanye nokugxila ezindaweni ezihlukene zesikhathi sokuthatha umthamo (15, 30, 60, 90 kanye ne-120 min) (Umfanekiso 7n, o).
Ukugxila kwe-Plasma kwe-TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, glucagon, ne-FGF21 kuboniswe kumagundane e-DIO (ao) abesilisa abadala ngemva kwezinsuku ezingu-33 zokudla.izinga lokushisa elicacisiwe.Amagundane awazange anikezwe amahora angama-2-3 ngaphambi kokuthatha isampula yegazi.Ukuhlolwa kokubekezelela i-glucose ngomlomo bekuhlukile njengoba kwenziwa ngethamo lesisindo somzimba esingu-2 g/kg ezinsukwini ezimbili ngaphambi kokuphela kocwaningo kumagundane azila ukudla amahora angama-5-6 futhi agcinwa ezingeni lokushisa elifanele izinsuku ezingama-31.Indawo engaphansi kwedatha yejika (o) iboniswa njengedatha ekhulayo (iAUC).Idatha yethulwa njengencazelo ± SEM.Amachashazi amelela amasampula ngamanye. *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.
Ukudluliswa kwedatha yegundane kubantu kuyinkinga eyinkimbinkimbi edlala indima ebalulekile ekuchazeni ukubaluleka kokubhekwa kumongo wocwaningo lwesayensi yezemvelo neyokwelapha.Ngenxa yezizathu zomnotho kanye nokwenza ucwaningo lube lula, amagundane avame ukugcinwa kuzinga lokushisa elilingana negumbi elingaphansi kwendawo yawo ye-thermoneutral, okuholela ekusebenziseni amasistimu ahlukahlukene ayisinxephezelo okuphila akhuphula izinga lokwenziwa kwe-metabolic futhi okungenzeka akhinyabeze ukuhumusha9.Ngakho-ke, ukuchayeka kwamagundane emakhazeni kungase kwenze amagundane amelane nokukhuluphala okubangelwa ukudla futhi kungase kuvimbele i-hyperglycemia kumagundane alashwe yi-streptozotocin ngenxa yokwanda kokuthuthwa kweglucose engancikile ku-insulin.Kodwa-ke, akucaci ukuthi ukuchayeka isikhathi eside kangakanani emazingeni okushisa ahlukahlukene afanelekile (kusuka egumbini kuye ku-thermoneutral) kuthinta i-homeostasis yamandla ehlukene yamagundane anesisindo esijwayelekile (ekudlani) kanye namagundane e-DIO (ku-HFD) kanye nemingcele ye-metabolic, kanye nezinga. lapho bakwazi ukulinganisa ukwanda kwe-EE nokwanda kokudla.Ucwaningo olunikezwe kulesi sihloko luhlose ukuletha ukucaca okuthile kulesi sihloko.
Sibonisa ukuthi esisindweni esivamile samagundane amadala kanye namagundane e-DIO angamaduna, i-EE ihlobene ngokuphambene nezinga lokushisa legumbi phakathi kuka-22 no-30°C.Ngakho, i-EE ku-22°C yayicishe ibe ngama-30% ngaphezu kuka-30°C.kuwo womabili amamodeli egundane.Kodwa-ke, umehluko obalulekile phakathi kwamagundane esisindo esivamile kanye namagundane e-DIO ukuthi kuyilapho amagundane esisindo esivamile ehambisana ne-EE emazingeni okushisa aphansi ngokulungisa ukudla okudlayo ngokufanele, ukudla okudlayo kwamagundane e-DIO kwahlukahluka emazingeni ahlukene.Amazinga okushisa ocwaningo ayefana.Ngemva kwenyanga eyodwa, amagundane e-DIO agcinwe ku-30°C athola isisindo somzimba esiningi namafutha amaningi kunamagundane agcinwe ku-22°C, kuyilapho abantu abavamile begcina izinga lokushisa elifanayo futhi isikhathi esifanayo abazange baholele emkhuhlaneni.umehluko oncike esisindweni somzimba.amagundane anesisindo.Uma kuqhathaniswa namazinga okushisa aseduze ne-thermoneutral noma izinga lokushisa legumbi, ukukhula ekamelweni lokushisa kubangele i-DIO noma amagundane anesisindo esivamile ekudleni okunamafutha aphezulu kodwa hhayi ekudleni kwegundane lesisindo esivamile ukuze athole isisindo esincane uma kuqhathaniswa.umzimba.Isekelwe ezinye izifundo17,18,19,20,21 kodwa hhayi yizo zonke22,23.
Ikhono lokudala i-microenvironment ukuze kuncishiswe ukulahlekelwa ukushisa kucatshangelwa ukuthi lishintshe ukungathathi hlangothi kokushisa kwesokunxele8, 12. Ocwaningweni lwethu, kokubili ukungezwa kwezinto zokuzalela nokufihla kunciphise i-EE kodwa akuzange kubangele ukungathathi hlangothi okushisayo kufika ku-28°C.Ngakho-ke, idatha yethu ayisekeli ukuthi iphuzu eliphansi le-thermoneutrality kumagundane amadala anedolo elilodwa, anezindlu ezicebile noma ezingenazo imvelo, kufanele libe ngu-26-28 ° C njengoba kubonisiwe8,12, kodwa lisekela ezinye izifundo ezibonisa ukushisa kwemvelo.amazinga okushisa angu-30°C endaweni ephansi amagundane7, 10, 24. Ukwenza izinto zibe nzima, iphoyinti le-thermoneutral kumagundane liboniswe ukuthi alimile phakathi nosuku njengoba liphansi ngesikhathi sesigaba sokuphumula (sokukhanya), okungenzeka ngenxa yekhalori ephansi. ukukhiqizwa ngenxa yomsebenzi kanye ne-thermogenesis eyenziwe ngokudla.Ngakho, esigabeni sokukhanya, iphuzu eliphansi lokungathathi hlangothi okushisayo liphenduka ~ 29 ° С, futhi esigabeni esimnyama, ~ 33 ° С25.
Ekugcineni, ubudlelwano phakathi kwezinga lokushisa le-ambient kanye nokusetshenziswa kwamandla okuphelele kunqunywa ukulahlwa kokushisa.Kulo mongo, isilinganiso sendawo engaphezulu nevolumu iyisinqumo esibalulekile sokuzwela okushisayo, okuthinta kokubili ukuchithwa kokushisa (indawo engaphezulu) kanye nokukhiqizwa kokushisa (ivolumu).Ngaphandle kwendawo engaphezulu, ukudluliswa kokushisa nakho kunqunywa ngokufakwa (izinga lokudlulisa ukushisa).Kubantu, isisindo samafutha singanciphisa ukulahlekelwa ukushisa ngokudala isithiyo sokuvikela ezungeze igobolondo lomzimba, futhi kuye kwaphakanyiswa ukuthi isisindo samafutha sibalulekile futhi ekufakeni ukushisa kwamagundane, ukwehlisa iphuzu le-thermoneutral nokunciphisa ukuzwela kwezinga lokushisa ngaphansi kwephuzu elishisayo elingathathi hlangothi ( umthambeka wejika).izinga lokushisa le-ambient uma liqhathaniswa ne-EE)12.Ucwaningo lwethu lwalungaklanyelwe ukuhlola ngokuqondile lobu budlelwano bokubeka ngoba idatha yokwakheka komzimba yaqoqwa izinsuku ezingu-9 ngaphambi kokuthi idatha yezindleko zamandla iqoqwe futhi ngenxa yokuthi isisindo samafutha asizange sizinzile kulo lonke ucwaningo.Nokho, njengoba isisindo esivamile namagundane e-DIO ane-EE ephansi ngo-30% ku-30°C kunaku-22°C naphezu kokungenani umehluko ophindwe ka-5 kusisindo samafutha, idatha yethu ayisekeli ukuthi ukukhuluphala kufanele kunikeze ukufakwa okuyisisekelo.isici, okungenani hhayi ebangeni lokushisa eliphenyiwe.Lokhu kuhambisana nezinye izifundo eziklanyelwe kangcono ukuhlola lokhu4,24.Kulezi zifundo, umphumela wokuvimbela ukukhuluphala wawuncane, kodwa uboya butholakale buhlinzeka ngama-30-50% wengqikithi yokushisa okushisayo4,24.Kodwa-ke, kumagundane afile, ukuqhutshwa kokushisa kukhuphuke cishe ngo-450% ngokushesha ngemva kokufa, okuphakamisa ukuthi umphumela wokushisa woboya uyadingeka ukuze kusebenze izindlela zomzimba, kuhlanganise ne-vasoconstriction.Ngaphezu komehluko wezinhlobo zoboya phakathi kwamagundane nabantu, umthelela ongemuhle wokuvikela ukukhuluphala kumagundane ungase futhi uthonywe ukucatshangelwa okulandelayo: Isici sokuvikela samafutha omuntu ikakhulukazi siqondiswa yi-subcutaneous fat mass (ubukhulu)26,27.Ngokuvamile kumagundane Angaphansi kwama-20% engqikithi yamafutha ezilwane28.Ukwengeza, isisindo samafutha esiphelele singase singabi ngisho nesilinganiso esincane kakhulu sokufakwa kwezinga lokushisa komuntu, njengoba kuye kwaphikiswana ngokuthi ukufakwa kwe-thermal okuthuthukisiwe kuxazululwa ukwanda okungenakugwemeka kwendawo engaphezulu (futhi ngenxa yalokho kwanda ukulahlekelwa ukushisa) njengoba isisindo samafutha sikhula..
Emagundaneni esisindo esivamile, ukugxila kwe-plasma okuzila ukudla kwe-TG, i-3-HB, i-cholesterol, i-HDL, i-ALT, ne-AST ayizange ishintshe emazingeni okushisa ahlukahlukene cishe amasonto angu-5, mhlawumbe ngenxa yokuthi amagundane ayesesimweni esifanayo sokulinganisa amandla.ayefana ngesisindo nokwakheka komzimba njengasekupheleni kocwaningo.Ngokuhambisana nokufana kwesisindo samafutha, kwakungekho mehluko kumazinga e-leptin e-plasma, noma ekuzileni kwe-insulin, i-C-peptide, ne-glucagon.Izimpawu ezengeziwe zitholwe kumagundane e-DIO.Nakuba amagundane ku-22 ° C nawo ayengenawo amandla asele aphelele kulesi sifundazwe (njengoba ethola isisindo), ekupheleni kocwaningo ayentula kakhulu amandla uma kuqhathaniswa namagundane akhuliswe ngo-30 ° C, ezimeni ezifana ama-ketones aphezulu.ukukhiqizwa ngumzimba (3-GB) kanye nokuncipha kokuhlushwa kwe-glycerol ne-TG ku-plasma.Kodwa-ke, umehluko oncike kumazinga okushisa ku-lipolysis awubonakali njengomphumela wezinguquko zangaphakathi kumafutha e-epididymal noma angu-inguinal, njengoshintsho ekuvezweni kwe-adipohormone-responsive lipase, njengoba i-FFA ne-glycerol ekhishwa emafutheni akhishwe kulawa madepho aphakathi Kwezinga lokushisa. amaqembu afana nomunye.Nakuba singazange siphenye ithoni yozwela ocwaningweni lwamanje, abanye bathole ukuthi (ngokusekelwe ekushayeni kwenhliziyo kanye nomfutho wegazi ovamile) ihlobene ngokuqondile nezinga lokushisa elizungezile kumagundane futhi cishe liphansi ku-30 ° C kunama-22 ° C 20% C Ngakho-ke, ukuhluka okuncike ekushiseni kwethoni ezwelayo kungase kubambe iqhaza ku-lipolysis esifundweni sethu, kodwa njengoba ukwanda kwethoni yozwela kuvuselela kunokuba kuvimbele i-lipolysis, ezinye izindlela zingase zivimbele lokhu kuncipha kwamagundane akhulisiwe.Indima engaba khona ekuqhekekeni kwamafutha omzimba.Izinga lokushisa legumbi.Ngaphezu kwalokho, ingxenye yomphumela ovuselelayo wethoni yokuzwela ku-lipolysis ixhunyaniswa ngokungaqondile ngokuvinjwa okuqinile kokukhiqizwa kwe-insulin, okugqamisa umphumela we-insulin ephazamisa ukwengezwa ku-lipolysis30, kodwa ocwaningweni lwethu, ithoni yokuzwela ye-plasma ye-plasma ne-C-peptide emazingeni okushisa ahlukene yaboniswa. akwanele ukuguqula i-lipolysis.Esikhundleni salokho, sithole ukuthi ukuhluka kwesimo samandla kungenzeka kube yimbangela enkulu kulo mehluko kumagundane e-DIO.Izizathu eziyisisekelo eziholela ekulawulweni okungcono kokudla nge-EE kumagundane esisindo esijwayelekile zidinga ucwaningo olwengeziwe.Nokho, ngokuvamile, ukudla kulawulwa yi-homeostatic kanye ne-hedonic cues31,32,33.Nakuba kunenkulumompikiswano ngokuthi iyiphi kulezi zimpawu ezimbili ebaluleke kakhulu ngokwesilinganiso, 31,32,33 kwaziwa kahle ukuthi ukusetshenziswa isikhathi eside kokudla okunamafutha amaningi kuholela ekuziphatheni kokudla okusekelwe enjabulweni okungahlobene ngandlela thile nokudla. i-homeostasis..– ukudla okulawulwayo34,35,36.Ngakho-ke, ukwanda kokuziphatha kokuphakelayo kwe-hedonic kwamagundane e-DIO aphathwe nge-45% HFD kungase kube esinye sezizathu ezenza lawa magundane angalinganisi ukudla ne-EE.Kuyathakazelisa ukuthi umehluko wesifiso sokudla kanye nama-hormone alawula ushukela wegazi nawo wabonwa kumagundane e-DIO alawulwa izinga lokushisa, kodwa hhayi kumagundane anesisindo esijwayelekile.Kumagundane e-DIO, amazinga e-plasma leptin anda ngezinga lokushisa kanye namazinga eglucagon ehla ngezinga lokushisa.Izinga lokushisa elingathonya ngalo ngokuqondile lo mehluko lifanelwe ukufundwa okwengeziwe, kodwa endabeni ye-leptin, ibhalansi yamandla engalungile futhi ngaleyo ndlela isisindo esiphansi samafutha kumagundane ku-22 ° C ngokuqinisekile idlale indima ebalulekile, njengoba isisindo samafutha kanye ne-plasma leptin ihlobene kakhulu37.Nokho, ukuchazwa kwesiginali yeglucagon kuyadida kakhulu.Njenge-insulin, ukukhiqizwa kweglucagon kwakuvinjwe kakhulu ukwanda kwethoni yozwelo, kodwa ithoni yozwela ephakeme kakhulu yabikezelwa ukuthi izoba seqenjini elingu-22°C, elalinokugxilisa okuphezulu kweglucagon ku-plasma.I-insulin ingenye isilawuli esinamandla se-plasma glucagon, futhi ukumelana ne-insulin kanye nohlobo lwe-2 yesifo sikashukela kuhlotshaniswa kakhulu nokuzila ukudla kanye ne-postprandial hyperglucagonemia 38,39.Nokho, amagundane e-DIO ocwaningweni lwethu nawo ayengezwani ne-insulin, ngakho-ke lokhu nakho kwakungeke kube yisici esiyinhloko ekwandeni kokusayina kweglucagon eqenjini le-22°C.Okuqukethwe kwamafutha esibindi nakho kuhlotshaniswa kahle nokwanda kokuhlushwa kwe-glucagon ku-plasma, izindlela zazo, ezingase zihlanganise ukumelana ne-glucagon yesibindi, ukwehla kokukhiqizwa kwe-urea, ukwanda kokugxila kwama-amino acid okujikelezayo, kanye nokwanda kwe-amino acid-stimulated glucagon secretion40,41, 42.Kodwa-ke, njengoba ukugxila okukhiphekayo kwe-glycerol ne-TG akuzange kuhluke phakathi kwamaqembu okushisa esifundweni sethu, lokhu futhi kwakungeke kube yisici esinamandla ekwandeni kokugxila kwe-plasma eqenjini le-22 ° C.I-Triiodothyronine (T3) idlala indima ebalulekile ekulinganiseni okuphelele kwe-metabolic kanye nokuqalwa kokuzivikela kwe-metabolic ngokumelene ne-hypothermia43,44.Ngakho-ke, ukuhlushwa kwe-plasma T3, okungenzeka kulawulwa izindlela ezimaphakathi, i-45,46 iyanda kokubili amagundane nakubantu ngaphansi kwezimo ezingaphansi kwe-thermoneutral47, nakuba ukwanda kwabantu kuncane, okuthandwa kakhulu kumagundane.Lokhu kuhambisana nokulahlekelwa ukushisa kwemvelo.Asizange silinganise ukugxila kwe-plasma T3 ocwaningweni lwamanje, kodwa ukugxila kungenzeka kube ngaphansi kweqembu le-30 ° C, elingase lichaze umphumela waleli qembu kumazinga e-plasma glucagon, njengoba thina (umfanekiso obuyekeziwe we-5a) nabanye sibonise ukuthi I-T3 inyusa i-plasma glucagon ngendlela encike kumthamo.Kuye kwabikwa ukuthi amahomoni egilo abangela inkulumo ye-FGF21 esibindini.Njenge-glucagon, ukugxila kwe-plasma FGF21 kuphinde kwanda ngokugxila kwe-plasma T3 (I-Supplementary Fig. 5b kanye ne-ref. 48), kodwa uma kuqhathaniswa ne-glucagon, ukugxila kwe-plasma ye-FGF21 ocwaningweni lwethu akuzange kuthinteke ukushisa.Izizathu eziyisisekelo zalokhu kungafani zidinga ukutadisha okuqhubekayo, kodwa ukungeniswa kwe-FGF21 eqhutshwa yi-T3 kufanele kwenzeke emazingeni aphezulu okuchayeka kwe-T3 uma kuqhathaniswa nempendulo ye-glucagon eqhutshwa yi-T3 (I-Supplementary Fig. 5b).
I-HFD ikhonjiswe ukuthi ihlotshaniswa kakhulu nokubekezelela ushukela okhubazekile kanye nokungazweli kwe-insulin (omaka) kumagundane akhuliswe ku-22°C.Nokho, i-HFD ayizange ihlotshaniswe nokubekezelela i-glucose ekhubazekile noma ukumelana ne-insulin lapho ikhule endaweni ye-thermoneutral (echazwe lapha ngokuthi i-28 °C) 19.Ocwaningweni lwethu, lobu budlelwano abuzange buphindwe kumagundane e-DIO, kodwa amagundane esisindo esijwayelekile agcinwe ku-30 ° C athuthukise kakhulu ukubekezelelwa kwe-glucose.Isizathu salo mehluko sidinga ucwaningo olwengeziwe, kodwa singathonywa yiqiniso lokuthi amagundane e-DIO ocwaningweni lwethu ayengazweli nge-insulin, ngokugxila kwe-C-peptide ye-plasma yokuzila nokugxila kwe-insulin izikhathi eziyi-12-20 ngaphezu kwamagundane esisindo esivamile.nasegazini esiswini esingenalutho.ukugxiliswa kweglucose okungaba ngu-10 mM (cishe u-6 mM ngesisindo somzimba esijwayelekile), okubonakala kushiya iwindi elincane ukuze uthole noma yimiphi imiphumela enenzuzo engaba khona yokuchayeka ezimeni ze-thermoneutral ukuze kuthuthukiswe ukubekezelela ushukela.Into engase idideke ukuthi, ngenxa yezizathu ezingokoqobo, i-OGTT yenziwa ekamelweni lokushisa.Ngakho-ke, amagundane agcinwe emazingeni okushisa aphakeme abe nokushaqeka okubandayo okungase kuthinte ukumuncwa/ukususwa kweglucose.Kodwa-ke, ngokususelwe ekugxilweni okufanayo kweglucose egazini lokuzila ukudla emaqenjini ahlukene okushisa, izinguquko kuzinga lokushisa le-ambient kungenzeka ukuthi aziyithinti kakhulu imiphumela.
Njengoba kushiwo ngaphambili, kusanda kugqanyiswa ukuthi ukukhulisa izinga lokushisa kwegumbi kungase kunciphise ukusabela okuthile ekucindezelekeni okubandayo, okungase kubuze ukudluliswa kwedatha yegundane kubantu.Kodwa-ke, akucaci ukuthi iliphi izinga lokushisa elilungile lokugcina amagundane ukuze alingise isayensi yokwakheka komzimba womuntu.Impendulo yalo mbuzo ingathonywa futhi umkhakha wokufunda kanye nesiphetho esifundwayo.Isibonelo salokhu umphumela wokudla ekuqongeleleni kwamafutha esibindi, ukubekezelela ushukela kanye nokungazweli kwe-insulin19.Mayelana nezindleko zamandla, abanye abacwaningi bakholelwa ukuthi i-thermoneutrality izinga lokushisa elilungile lokukhulisa, njengoba abantu bedinga amandla amancane engeziwe ukuze balondoloze izinga lokushisa lomzimba wabo eliyisisekelo, futhi bachaza izinga lokushisa lethanga elilodwa lamagundane amadala njengo-30°C7,10.Abanye abacwaningi bakholelwa ukuthi izinga lokushisa eliqhathaniswa nalelo abantu abajwayele ukulithola ngamagundane amadala edolweni elilodwa lingu-23-25°C, njengoba bathole ukuthi izinga lokushisa lingama-26-28°C futhi lisekelwe ekubeni abantu bephansi cishe ngo-3°C.izinga lokushisa labo eliphansi elibucayi, elichazwa lapha ngokuthi ngu-23°C, lithe uku-8.12.Ucwaningo lwethu luhambisana nezinye izifundo eziningana ezisho ukuthi ukungathathi hlangothi okushisayo akutholakali ku-26-28 ° C4, 7, 10, 11, 24, 25, okubonisa ukuthi i-23-25 ° C iphansi kakhulu.Esinye isici esibalulekile okufanele sicatshangelwe mayelana nezinga lokushisa legumbi kanye ne-thermoneutrality kumagundane indlu eyodwa noma yeqembu.Lapho amagundane ehlaliswa ngamaqembu kunokuba ahlaliswe ngamanye, njengasocwaningweni lwethu, ukuzwela kwezinga lokushisa kwancipha, mhlawumbe ngenxa yokuminyana kwezilwane.Nokho, izinga lokushisa lasekamelweni lalisengaphansi kwe-LTL engu-25 lapho kusetshenziswa amaqembu amathathu.Mhlawumbe umehluko obaluleke kakhulu we-interspecies kulokhu ukubaluleka kobuningi bomsebenzi we-BAT njengesivikelo ngokumelene ne-hypothermia.Ngakho-ke, ngenkathi amagundane enxephezela kakhulu ukulahlekelwa kwawo kwekhalori ephakeme ngokukhulisa umsebenzi we-BAT, ongaphezu kwe-60% EE ku-5 ° C kuphela, i-51,52 umnikelo womsebenzi we-BAT womuntu ku-EE wawuphakeme kakhulu, uncane kakhulu.Ngakho-ke, ukunciphisa umsebenzi we-BAT kungase kube indlela ebalulekile yokwandisa ukuhumusha komuntu.Ukulawulwa komsebenzi we-BAT kuyinkimbinkimbi kodwa kuvame ukuqondiswa yimiphumela ehlangene yokuvuselela i-adrenergic, amahomoni e-thyroid kanye ne-UCP114,54,55,56,57 expression.Idatha yethu ibonisa ukuthi izinga lokushisa lidinga ukukhushulwa ngaphezu kuka-27.5°C uma kuqhathaniswa namagundane ku-22°C ukuze kutholwe umehluko ekukhulumeni kwezakhi zofuzo ze-BAT ezinesibopho sokusebenza/ukwenza kusebenze.Nokho, umehluko otholakala phakathi kwamaqembu ku-30 no-22°C awuzange ubonise njalo ukwanda komsebenzi we-BAT eqenjini le-22°C ngoba i-Ucp1, i-Adrb2 ne-Vegf-a yayilawulwa phansi eqenjini le-22°C.Imbangela yale miphumela engalindelekile isazotholakala.Okunye okungenzeka ukuthi ukuvezwa kwawo okukhulayo kungase kungabonisi isignali yezinga lokushisa eliphakeme legumbi, kodwa umphumela omkhulu wokuwasusa ku-30°C aye ku-22°C ngosuku awakhipha ngalo (amagundane ahlangabezane nalokhu emizuzwini engu-5-10 ngaphambi kokusuka) .).
Umkhawulo ojwayelekile wocwaningo lwethu ukuthi sifunde amagundane abesilisa kuphela.Olunye ucwaningo luphakamisa ukuthi ubulili bungase bucatshangelwe okubalulekile ezinkomba zethu eziyinhloko, njengoba amagundane esifazane anedolo elilodwa ezwela kakhulu izinga lokushisa ngenxa ye-thermal conductivity ephakeme kanye nokugcina amazinga okushisa ayisisekelo alawulwa ngokuqinile.Ukwengeza, amagundane wesifazane (ku-HFD) abonise ukuhlangana okukhulu kokuthatha amandla ne-EE ku-30 °C uma kuqhathaniswa namagundane wesilisa adle amagundane amaningi obulili obufanayo (20 °C kulokhu) 20.Ngakho-ke, kumagundane abesifazane, okuqukethwe kwe-subthermonetral okunomthelela kuphezulu, kodwa kunephethini efanayo neyamagundane abesilisa.Ocwaningweni lwethu, sigxile kumagundane eduna anedolo elilodwa, njengoba lezi kuyizimo lapho iningi lezifundo ze-metabolic ezihlola i-EE zenziwa ngaphansi kwazo.Omunye umkhawulo wocwaningo lwethu ukuthi amagundane ayesekudleni okufanayo kulo lonke ucwaningo, okuvimbela ukutadisha ukubaluleka kwegumbi lokushisa lokuguquguquka kwe-metabolic (njengoba kulinganiswa nezinguquko ze-RER zoshintsho lokudla ekuqanjweni okuhlukahlukene kwama-macronutrient).kumagundane esifazane nabesilisa agcinwe ku-20°C uma kuqhathaniswa namagundane ahambisanayo agcinwe ku-30°C.
Sengiphetha, ucwaningo lwethu lukhombisa ukuthi, njengakwezinye izifundo, i-lap 1 amagundane esisindo esijwayelekile asezingeni eliphansi kune-27.5 ° C ebikezelwe.Ukwengeza, ucwaningo lwethu lubonisa ukuthi ukukhuluphala akuyona into enkulu yokuvikela amagundane anesisindo esivamile noma i-DIO, okuholela ekushiseni okufanayo: Izilinganiso ze-EE ku-DIO namagundane esisindo esivamile.Nakuba ukudla kwamagundane esisindo esivamile kwakuhambisana ne-EE futhi ngaleyo ndlela kugcinwe isisindo somzimba esizinzile phezu kwalo lonke uhla lokushisa, ukudla kwamagundane e-DIO kwakufana emazingeni okushisa ahlukene, okuholela esilinganisweni esiphezulu samagundane ku-30 ° C. .ku-22°C ithole isisindo somzimba esengeziwe.Sekukonke, izifundo ezihlelekile ezihlola ukubaluleka okungaba khona kokuphila ngaphansi kwamazinga okushisa e-thermoneutral ziyaqinisekiswa ngenxa yokungabekezeleleki okubi phakathi kwegundane nezifundo zabantu.Isibonelo, ezifundweni zokukhuluphala ngokweqile, incazelo eyingxenye yokuhumusha okuvame ukumpofu kungase kube ngenxa yokuthi izifundo zokulahlekelwa kwesisindo se-murine zivame ukuqhutshwa ezilwaneni ezicindezelekile ezibandayo ezigcinwe ekamelweni lokushisa ngenxa yokwanda kwe-EE.Ukwehla kwesisindo okweqile uma kuqhathaniswa nesisindo somzimba esilindelekile somuntu, ikakhulukazi uma indlela yokwenza incike ekwandiseni i-EE ngokwandisa umsebenzi we-BAP, osebenza kakhulu futhi ocushwe ekamelweni lokushisa kunama-30 ° C.
Ngokuhambisana Nomthetho Wokuhlola Wezilwane WaseDanish (1987) kanye Nezikhungo Zezempilo Zikazwelonke (Ukushicilelwa No. 85-23) kanye Nesivumelwano SaseYurophu Sokuvikela I-Vertebrate esetshenziselwa Izinjongo Zokuhlola Nezinye Zesayensi (Council of Europe No. 123, Strasbourg , 1985).
Amagundane angama-C57BL/6J wesilisa anamasonto angamashumi amabili ubudala atholwe kwa-Janvier Saint Berthevin Cedex, e-France, futhi anikezwa i-ad libitum standard chow (Altromin 1324) kanye namanzi (~22°C) ngemva kwehora elingu-12:12 ukukhanya:umjikelezo omnyama.izinga lokushisa lekamelo.Amagundane e-DIO yesilisa (amaviki angu-20) atholwe kumhlinzeki ofanayo futhi anikezwa i-ad libitum ukufinyelela ku-45% yokudla okunamafutha aphezulu (Cat. No. D12451, Research Diet Inc., NJ, USA) kanye namanzi ngaphansi kwezimo zokukhulisa.Amagundane ajwayela imvelo isonto ngaphambi kokuqala kocwaningo.Ezinsukwini ezimbili ngaphambi kokudluliselwa ohlelweni lwe-calorimetry olungaqondile, amagundane alinganiswa, angaphansi kwe-MRI scanning (EchoMRITM, TX, USA) futhi ahlukaniswa ngamaqembu amane ahambisana nesisindo somzimba, amafutha kanye nesisindo somzimba esivamile.
Umdwebo wesithombe somklamo wocwaningo uboniswa kuMfanekiso 8. Amagundane adluliselwe kusistimu ye-calorierimetry engaqondile elawulwa izinga lokushisa evaliwe futhi elawulwa izinga lokushisa kwa-Sable Systems Internationals (Nevada, USA), ehlanganisa iziqaphi zekhwalithi yokudla namanzi kanye nohlaka lwe-Promethion BZ1 olurekhodiwe. amazinga omsebenzi ngokulinganisa amakhefu emishayo.XYZ.Amagundane (n = 8) ahlaliswa ngawodwana ku-22, 25, 27.5, noma 30°C kusetshenziswa okombhede kodwa kungekho mpahla yokufihla ikhanda ekukhanyeni kwamahora angu-12:12:umjikelezo omnyama (ukukhanya: 06:00– 18:00) .2500ml/min.Amagundane ajwayele izinsuku ezingu-7 ngaphambi kokubhaliswa.Okuqoshiwe kwaqoqwa izinsuku ezine zilandelana.Ngemva kwalokho, amagundane agcinwa emazingeni okushisa afanele ku-25, 27.5, no-30°C izinsuku ezengeziwe ezingu-12, okwathi ngemva kwalokho ingqamuzana igxilisa ingqondo yenezelwa njengoba kuchazwe ngezansi.Phakathi naleso sikhathi, amaqembu amagundane agcinwe ku-22 ° C agcinwa kulokhu kushisa ezinye izinsuku ezimbili (ukuze kuqoqwe idatha entsha yesisekelo), bese izinga lokushisa likhuphuka ngezinyathelo ze-2 ° C njalo ngemva kwezinsuku ezimbalwa ekuqaleni kwesigaba sokukhanya ( 06:00) kuze kufike ku-30 °C Ngemva kwalokho, izinga lokushisa lehliswa laya ku-22°C futhi idatha yaqoqwa ezinye izinsuku ezimbili.Ngemva kwezinsuku ezimbili ezengeziwe zokurekhoda ku-22 ° C, izikhumba zengezwa kuwo wonke amaseli kuwo wonke amazinga okushisa, futhi ukuqoqwa kwedatha kwaqala ngosuku lwesibili (usuku lwe-17) kanye nezinsuku ezintathu.Ngemva kwalokho (usuku lwama-20), okwakhiwe isidleke (8-10 g) kwengezwa kuwo wonke amaseli ekuqaleni komjikelezo wokukhanya (06:00) futhi idatha yaqoqwa ezinye izinsuku ezintathu.Ngakho-ke, ekupheleni kocwaningo, amagundane agcinwe ku-22 ° C agcinwa kulokhu kushisa izinsuku ezingu-21/33 futhi ku-22 ° C izinsuku ezingu-8 zokugcina, kuyilapho amagundane kwamanye amazinga okushisa agcinwa kulokhu kushisa izinsuku ezingu-33./33 izinsuku.Amagundane adliwe ngesikhathi socwaningo.
Isisindo esijwayelekile namagundane e-DIO alandele izinqubo ezifanayo zocwaningo.Ngosuku -9, amagundane akalwa, i-MRI iskenwa, futhi yahlukaniswa ngamaqembu afana nesisindo somzimba kanye nokwakheka komzimba.Ngosuku -7, amagundane adluliselwa kuhlelo lokushisa oluvaliwe olulawulwa ngokungaqondile lwe-calorimetry system eyenziwe yi-SABLE Systems International (Nevada, USA).Amagundane ahlaliswa ngawodwana ngezingubo zokulala kodwa ngaphandle kwezinto zokuzalela noma zokukhosela.Izinga lokushisa libekwe ku-22, 25, 27.5 noma 30 °C.Ngemuva kwesonto elilodwa lokujwayela (izinsuku -7 kuya ku-0, izilwane azizange ziphazamiseke), idatha yaqoqwa ngezinsuku ezine ezilandelanayo (izinsuku ezingu-0-4, idatha eboniswe ku-FIGS. 1, 2, 5).Ngemva kwalokho, amagundane agcinwe ku-25, 27.5 kanye no-30 ° C agcinwa ngaphansi kwezimo eziqhubekayo kuze kube usuku lwe-17.Ngesikhathi esifanayo, izinga lokushisa eqenjini le-22 ° C lanyuswa ngezikhathi ze-2 ° C njalo ngemva kolunye usuku ngokulungisa umjikelezo wokushisa (06:00 h) ekuqaleni kokuchayeka kokukhanya (idatha iboniswa ku-Fig. 1) .Ngosuku lwe-15, izinga lokushisa lehla laya ku-22°C futhi izinsuku ezimbili zedatha zaqoqwa ukuze kuhlinzekwe idatha eyisisekelo yokwelashwa okwalandela.Izikhumba zengezwa kuwo wonke amagundane ngosuku lwe-17, futhi izinto zokuzalela zanezelwa ngosuku lwama-20 (Fig. 5).Ngosuku lwama-23, amagundane akalwa futhi ahlolwa nge-MRI, bese eshiywa yedwa amahora angama-24.Ngosuku lwe-24, amagundane azila ukudla kusukela ekuqaleni kwe-photoperiod (06:00) futhi athola i-OGTT (2 g / kg) ngo-12: 00 (amahora angu-6-7 wokuzila ukudla).Ngemva kwalokho, amagundane abuyiselwa ezimeni zawo ezihlukene ze-SABLE futhi abulawa ngosuku lwesibili (usuku lwama-25).
Amagundane e-DIO (n = 8) alandele inqubo efanayo njengamagundane esisindo esivamile (njengoba kuchazwe ngenhla nakuMfanekiso 8).Amagundane agcine u-45% we-HFD kulo lonke ucwaningo lwezindleko zamandla.
I-VO2 ne-VCO2, kanye nomfutho womhwamuko wamanzi, zarekhodwa ngemvamisa ye-1 Hz ne-cell time constant engu-2.5 min.Ukudla kanye namanzi okuthathwayo kwaqoqwa ngokurekhoda okuqhubekayo (1 Hz) kwesisindo samabhakede okudla namanzi.Imonitha yekhwalithi esetshenzisiwe ibike ukulungiswa okungu-0.002 g.Amaleveli omsebenzi arekhodwa kusetshenziswa imonitha ye-3D XYZ ye-beam, idatha yaqoqwa ngokulungiswa kwangaphakathi okungu-240 Hz futhi yabikwa njalo ngesekhondi ukuze kulinganiswe isamba sebanga elihanjiwe (m) ngokulungiswa kwendawo okusebenzayo okungu-0.25 cm.Idatha yacutshungulwa nge-Sable Systems Macro Interpreter v.2.41, ibala i-EE ne-RER futhi ihlunga izinto eziphuma ngaphandle (isb., imicimbi yokudla okungamanga).Umhumushi omkhulu ulungiselelwe ukuthi akhiphe idatha yawo wonke amapharamitha njalo ngemizuzu emihlanu.
Ngaphezu kokulawula i-EE, izinga lokushisa le-ambient lingaphinda lilawule ezinye izici ze-metabolism, okuhlanganisa i-postprandial glucose metabolism, ngokulawula ukukhiqizwa kwamahomoni ahlanganisa i-glucose.Ukuhlola le nkoleloze, ekugcineni siqedele ukuhlola izinga lokushisa lomzimba ngokuchukuluza amagundane esisindo esivamile nge-DIO oral glucose load (2 g/kg).Izindlela zichazwe ngokuningiliziwe ezintweni ezengeziwe.
Ekupheleni kocwaningo (usuku lwama-25), amagundane azila ukudla amahora angu-2-3 (kusukela ngo-06: 00), abulawa izinzwa nge-isoflurane, futhi opha ngokuphelele nge-retroorbital venipuncture.Ukulinganisa inani lama-lipids e-plasma namahomoni nama-lipids esibindi kuchazwa Kwezinto Ezingeziwe.
Ukuze kuphenywe ukuthi izinga lokushisa legobolondo liyabangela yini izinguquko zangaphakathi kuzicubu ze-adipose ezithinta i-lipolysis, izicubu ze-inguinal ne-epididymal adipose zakhishwa ngokuqondile kumagundane ngemva kwesigaba sokugcina sokopha.Ama-tissue acutshungulwa kusetshenziswa i-ex vivo lipolysis assay esanda kuthuthukiswa echazwe ku-Supplementary Methods.
Izicubu ze-adipose ezinsundu (BAT) zaqoqwa ngosuku lokuphela kocwaningo futhi zacutshungulwa njengoba kuchazwe ezindleleni zokwengeza.
Idatha yethulwa njengencazelo ± SEM.Amagrafu adalwe ku-GraphPad Prism 9 (La Jolla, CA) futhi izithombe zahlelwa ku-Adobe Illustrator (Adobe Systems Incorporated, San Jose, CA).Ukubaluleka kwezibalo kwahlolwa ku-GraphPad Prism futhi kwahlolwa ngokuhlolwa kwe-t okubhangqiwe, izilinganiso eziphindaphindiwe ze-ANOVA yendlela eyodwa/indlela-embili elandelwa uhlolo lokuqhathanisa okuningi kuka-Tukey, noma i-ANOVA engabhanqiwe yendlela eyodwa elandelwa ukuhlolwa kokuqhathanisa okuningi kukaTukey njengoba kudingeka.Ukusatshalaliswa kwe-Gaussian kwedatha kwaqinisekiswa ukuhlolwa kokujwayelekile kwe-D'Agostino-Pearson ngaphambi kokuhlolwa.Usayizi wesampula ukhonjiswe esigabeni esihambelanayo sesigaba esithi "Imiphumela", kanye nakunganekwane.Ukuphindaphinda kuchazwa njenganoma yisiphi isilinganiso esithathwe esilwaneni esifanayo (ku-vivo noma kusampula yethishu).Ngokuphathelene nokuphindaphindeka kwedatha, ukuhlobana phakathi kwezindleko zamandla nezinga lokushisa kwecala kwaboniswa ezifundweni ezine ezizimele kusetshenziswa amagundane ahlukene anomklamo wocwaningo ofanayo.
Izivumelwano zokuhlola ezinemininingwane, izinto zokwakha, nedatha eluhlaza iyatholakala ngesicelo esiphusile esivela kumbhali oholayo u-Rune E. Kuhre.Lolu cwaningo aluzange lukhiqize ama-reagents amasha ahlukile, imigqa yezilwane ezishintshashintshayo/yeseli, noma idatha elandelanayo.
Ukuze uthole ulwazi olwengeziwe mayelana nesakhiwo socwaningo, bheka i-Nature Research Report abstract exhunywe kulesi sihloko.
Yonke idatha yenza igrafu.Oku-1-7 kufakwe endaweni yokugcina imininingwane yeSayensi, inombolo yokungena: 1253.11.sciencedb.02284 noma https://doi.org/10.57760/sciencedb.02284.Idatha eboniswe ku-ESM ingase ithunyelwe ku-Rune E Kuhre ngemva kokuhlolwa okunengqondo.
Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Izilwane zaselabhorethri njengezibonelo zokukhuluphala komuntu. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Izilwane zaselabhorethri njengezibonelo zokukhuluphala komuntu.Nilsson K, Raun K, Yang FF, Larsen MO.kanye nezilwane ze-Tang-Christensen M. Laboratory njengezibonelo zokukhuluphala komuntu. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. 实验动物作為人类肥胖的替代模型. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Izilwane zokuhlola njengemodeli ebambele yabantu.Nilsson K, Raun K, Yang FF, Larsen MO.kanye nezilwane ze-Tang-Christensen M. Laboratory njengezibonelo zokukhuluphala kubantu.I-Acta Pharmacology.ubugebengu 33, 173–181 (2012).
Gilpin, DA Ukubalwa kwe-Mie entsha engaguquki kanye nokuhlolwa kosayizi wokusha.Burns 22, 607–611 (1996).
Gordon, SJ Uhlelo lwe-mouse thermoregulatory: imithelela yalo ekudluliselweni kwedatha ye-biomedical kubantu.i-physiology.Ukuziphatha.179, 55-66 (2017).
Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Awukho umthelela ovimbela ukukhuluphala. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Awukho umthelela ovimbela ukukhuluphala.Fischer AW, Chikash RI, von Essen G., Cannon B., kanye noNedergaard J. Awukho umthelela wokuzihlukanisa wokukhuluphala. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. 肥胖没有绝缘作用。 Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Ожирение не имеет изолирующего эффекта. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Ukukhuluphala akunawo umthelela wokuhlukanisa.Yebo.J. Physiology.uhlelo lwe-endocrine.umzimba.311, E202–E213 (2016).
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Nakhon, KJ et al.Izinga lokushisa eliphansi elibucayi kanye ne-thermogenesis ebangelwa ukubanda kwakuhlobene ngokuphambene nesisindo somzimba kanye nesilinganiso se-basal metabolic kubantu abanomzimba omncane nabakhuluphele ngokweqile.J. Ngemfudumalo.isayensi yezinto eziphilayo.69, 238–248 (2017).
Fischer, AW, Cannon, B. & Nedergaard, J. Amazinga okushisa afanelekile ezindlu ukuze amagundane alingise indawo eshisayo yabantu: Ucwaningo lokuhlola. Fischer, AW, Cannon, B. & Nedergaard, J. Amazinga okushisa afanelekile ezindlu ukuze amagundane alingise indawo eshisayo yabantu: Ucwaningo lokuhlola.I-Fischer, AW, Cannon, B., kanye ne-Nedergaard, J. Amazinga okushisa aphakeme endlu ukuze amagundane alingise indawo eshisayo yabantu: Ucwaningo lokuhlola. 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.I-Fisher AW, Cannon B., kanye ne-Nedergaard J. Izinga lokushisa elilungile lezindlu lamagundane alingisa indawo eshisayo yabantu: Ucwaningo lokuhlola.Moore.umzimba.7, 161–170 (2018).
U-Keijer, J., Li, M. & Speakman, JR Iliphi izinga lokushisa elingcono kakhulu lezindlu ongahumushela ukuhlolwa kwegundane kubantu? U-Keijer, J., Li, M. & Speakman, JR Iliphi izinga lokushisa elingcono kakhulu lezindlu ongahumushela ukuhlolwa kwegundane kubantu?U-Keyer J, u-Lee M no-Speakman JR Iliphi izinga lokushisa elingcono kakhulu legumbi lokudlulisa ukuhlolwa kwegundane kubantu? Keijer, J., Li, M. & Speakman, JR 将小鼠实验转化為人类的最佳外壳温度是多少? Keijer, J., Li, M. & Speakman, JRU-Keyer J, u-Lee M kanye no-Speakman JR Iliphi izinga lokushisa elifanele legobolondo lokudlulisela ukuhlolwa kwegundane kubantu?Moore.umzimba.25, 168–176 (2019).
Seeley, RJ & MacDougald, OA Amagundane njengamamodeli wokuhlola wesayensi yokwakheka komzimba womuntu: lapho amadigri ambalwa kuzinga lokushisa kwezindlu kubalulekile. Seeley, RJ & MacDougald, OA Amagundane njengamamodeli wokuhlola wesayensi yokwakheka komzimba womuntu: lapho amadigri ambalwa kuzinga lokushisa kwezindlu kubalulekile. Seeley, RJ & MacDougald, OA Мыши как экспериментальные модели для физиологии человека: когда несколько градусов в жилище имеют знание. Seeley, RJ & MacDougald, OA Amagundane njengamamodeli okuhlola okusebenza komzimba womuntu: lapho amadigri ambalwa endaweni yokuhlala enza umehluko. 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 amagundane njengemodeli yokuhlola yefiziyoloji yomuntu: lapho amadigri ambalwa okushisa kwegumbi abalulekile.National metabolism.3, 443–445 (2021).
Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo yombuzo othi "Iliphi izinga lokushisa elingcono kakhulu lezindlu ukuze uhumushe ukuhlolwa kwegundane kubantu?" Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo yombuzo othi "Iliphi izinga lokushisa elingcono kakhulu lezindlu ukuze uhumushe ukuhlolwa kwegundane kubantu?" Fischer, AW, Cannon, B. & Nedergaard, J. Impendulo yombuzo othi “Iliphi izinga lokushisa elingcono kakhulu legumbi lokudlulisela ukuhlolwa kwegundane kubantu?” Fischer, AW, Cannon, B. & Nedergaard, J. 问题的答案“将小鼠实验转化為人类的最佳外壳温度是多少?” Fischer, AW, Cannon, B. & Nedergaard, J.UFisher AW, Cannon B., kanye noNedergaard J. Izimpendulo embuzweni othi “Iyini izinga lokushisa elilungile legobolondo lokudlulisela ukuhlolwa kwegundane kubantu?”Yebo: i-thermoneutral.Moore.umzimba.26, 1-3 (2019).
Isikhathi sokuthumela: Oct-28-2022