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Iningi lezifundo ze-metabolic egumeni zenziwa emazingeni okushisa asekamelweni, yize ngaphansi kwalezi zimo, ngokungafani nabantu, amagundane asebenzisa amandla amaningi okugcina izinga lokushisa langaphakathi. Lapha, sichaza ukukhuluphala okujwayelekile kanye nokudla okubangelwa kokudla (i-DIO) ku-C57bl / 6J Mice Fed Chow Chow noma i-45% yokudla okuphezulu okuphezulu, ngokulandelana. Amagundane abekwa izinsuku ezingama-33 ngo-22, 25, 27.5 no-30 ° C. ohlelweni olungaqondile lwekhalori. Sibonisa ukuthi ukusetshenziswa kwemali kwamandla kwandisa ngokuqondile kusuka ku-30 ° C kuya ku-22 ° C futhi kungama-30% aphezulu ku-22 ° C ku-22 ° C kuwo womabili amamodeli wegundane. Kumagundane ajwayelekile, ukudla okuphikisayo okulwa yi-ee. Ngakolunye uhlangothi, amagundane e-DIO awazange anciphise ukudla lapho u-Ee wehla. Ngakho-ke, ekugcineni kocwaningo, amagundane angu-30 ° C abenesisindo somzimba esiphakeme, isisindo samafutha kanye ne-plasma glycerol kanye ne-triglycerides kunamagundane angu-22 ° C. Ukungalingani ku-Dio Mice kungenzeka ngenxa yokudla okusekelwe ekujabuliseni.
Igundane liyimodeli yezilwane esetshenziswa kakhulu yocwaningo lwe-human physiology kanye ne-pathophysiology, futhi imvamisa iyisilwane esizenzakalelayo esisetshenziswa ezigabeni zokuqala zokutholwa kwezidakamizwa nentuthuko. Kodwa-ke, amagundane ahluka kubantu ngezindlela eziningana ezibalulekile zomzimba, futhi ngenkathi ukukala kwe-allometric kungasetshenziswa ngezinga elithile ukuhumusha kubantu, umehluko omkhulu phakathi kwamagundane futhi abantu bahlala e-homeostasis yamandla. Lokhu kukhombisa ukungahambisanisisekelo okubalulekile. Isisindo somzimba esivamile samagundane asendulo okungenani isikhathi esingaphansi kwenkulungwane kunaleso sabantu abadala (50 g vs. 50 kg), nendawo engaphezulu kwesilinganiso esiningi iyehluka ngezikhathi ezingama-400 ngenxa yokuguqulwa kwe-geometric engekho emthethweni ngenxa ye-mee . I-Equation 2. Ngenxa yalokho, amagundane alahlekelwa kakhulu ukushisa okuhlobene nevolumu yawo, ngakho-ke azwela kakhulu ekushiseni, futhi athambekele kakhulu ku-hypothermia, futhi abe nesilinganiso esijwayelekile se-basabother amahlandla ayishumi. Ekushiseni kwegumbi elijwayelekile (~ 22 ° C), amagundane kufanele akhuphule izindleko zawo zamandla (ee) cishe ngama-30% ukuze alondoloze izinga lokushisa lomzimba eliyisisekelo. Emazingeni okushisa aphansi, i-ee yandisa ngokwengeziwe cishe ngama-50% no-100% ngo-15 no-7 ° C ngokuqhathaniswa ne-22 ° C. Ngakho-ke, izimo ezijwayelekile zezindlu zikunxenxa ukuphendula okubandayo kwengcindezi, ebingahlehlisa ukuguqulwa kwemiphumela yegundane kubantu, ngoba abantu abaphila emiphakathini yabo (ngoba indawo yethu yokulinganisa indawo ephansi yevolumu isenza sizwele kancane izinga lokushisa, njengoba sakha indawo ye-thermoneUTral (TNZ) esizungeze i-US. Ee ngaphezulu kwe-Basal Metabolic Rate) Spans ~ 19 kuya ku-30 ° C6, ngenkathi amagundane enebhande eliphakeme nelincane Ukuthatha kuphela 2-4 ° C7,8 Eqinisweni, lesi sici esibalulekile sitholile ukunakwa okukhulu eminyakeni yamuva nje, 7,8,9,10,11,12 futhi kuphakanyiswe ukuthi ezinye "umehluko wezinhlobo" zingancishiswa ngokwanda Amazinga okushisa we-Shell 9. Kodwa-ke, akukho ukuvumelana kwebanga lokushisa elikha i-thermonetrality egunjini. Ngakho-ke, ukuthi ngabe amazinga okushisa aphansi abuhlu olusezingeni eliphansi egunjini elilodwa ledolo liseduze kuka-25 ° C noma eduze kuka-30 ° C4, 7, 8, 10, 12 kuhlala kuxabana. Amanye amapharamitha we-metabolic akhawulelwe amahora amaningi ezinsukwini, ngakho-ke izinga lokuvezwa isikhathi eside kumazinga okushisa ahlukahlukene lingathinta amapharamitha we-metabolic afana nesisindo somzimba akucaci. Ukusetshenziswa, ukusetshenziswa kwe-substrate, ukubekezelela i-glucose, kanye ne-plasma lipid kanye nama-glucose ukugxila kanye nama-hormone asetshenziswayo. Ngaphezu kwalokho, kudingeka ucwaningo olwengeziwe ukuze uqiniseke ukuthi ukudla kungathonya kangakanani lezi zinhlaka (amagundane e-dio ekudleni okunamafutha amaningi kungahle kuthathwe ekudleni okusekelwe ebumnandi (heedonic)). Ukuhlinzeka ngolwazi oluthe xaxa ngalesi sihloko, sihlolisise umphumela wokuvuselela amazinga okushisa kumapharamitha we-metabolic avered kumagundane ajwayelekile wesisindo sabantu abasezingeni eliphakeme kakhulu lokudla kanye nokudla okuphezulu kokudla (i-DIO). Amagundane agcinwe ngo-22, 25, 27.5, noma ama-30 ° C okungenani amasonto amathathu. Amazinga okushisa angaphansi kwama-22 ° C awafundiswanga ngoba izindlu ezijwayelekile zezilwane akuvamile ngaphansi kwezinga lokushisa legumbi. Sithole ukuthi amagundane ajwayelekile anesisindo esijwayelekile kanye ne-single-realidricle doice aphendule ngokushintshana ekushiseni okugcwele maqondana ne-ee futhi kungakhathalekile ukuthi kunesimo sokubekezela (esinezindawo zokubekelela / ezingenayo). Kodwa-ke, ngenkathi amagundane ajwayelekile anesisindo alungisa ukudla kwawo ngokusho kwe-e, ukudla okudlayo kwe-dio amagundane kwakungamele ngokuzimela kwe-ee, okuholela emathukeni athola isisindo esithe xaxa. Ngokusho kwemininingwane yesisindo somzimba, ukugxila kwe-plasma yama-lipids kanye nezidumbu ze-ketone kubonise ukuthi amacecu ama-dio at 30 ° C abese ukulinganisela kwamandla okuhle kunamagundane angu-22 ° C. Izizathu eziyisisekelo zomehluko ekulinganisweni kwemali yokudla namandla phakathi kwesisindo esijwayelekile kanye ne-dio mice ezidinga ukutadisha okwengeziwe, kepha kungahle kuhlobane nezinguquko ze-dio amagundane kanye nomphumela wokudla okunenjabulo ngenxa yokudla okuthelelekile.
I-EE yandisa ngokuqondile kusuka kuma-30 kuye ku-22 ° C futhi yayingama-30% aphezulu ngo-22 ° C ngokuqhathaniswa no-30 ° C (Fig. 1a, b). Izinga lokushintshaniswa kokuphefumula (i-RER) lizimele lokushisa (umkhiwane 1c, d). Ukudla kokudla bekuhambisane namandla e-EE futhi kwandiswe ngokuncipha kokushisa (futhi ~ 30% ngaphezulu ngo-22 ° C uma kuqhathaniswa nama-30 ° C (FIG. 1). Izinga lamanzi. 1g). -To).
Amagundane abesilisa (C57BL / 6J, amasonto angama-20 ubudala, izindlu ngazinye, n = 7) ezazigcinwe emakhejini we-metabolic ngo-22 ° C. ngesonto elilodwa ngaphambi kokuqala kwesifundo. Ezinsukwini ezimbili ngemuva kweqoqo lemininingwane yangemuva, izinga lokushisa lakhuliswa ekukhuphukeni okungu-2 ° C ngo-06: 00 amahora ngosuku (ukuqala kwesigaba sokukhanya). Idatha yethulwa njengephutha elijwayelekile ± Iphutha elijwayelekile lokusho, kanye nesigaba esimnyama (18: 00-06: 00 H) kumelwe yibhokisi elimpunga. Ukusetshenziswa kwemali (Kcal / H), Bonke Imali Eness Energy Eness Eats Energy Exerticition emazingeni okushisa ahlukahlukene (kcal / 24 h), c rate yokuvimbela ukushintshanisa (vco2 / vo2: 0.7-1.0), 2 (VCO2 / VO2) (Inani le-zero lichazwa njenge-0.7). E COLELATION Food Ukudla (G), F 24h inani lokudla okuphelele, g 24h inani lamanzi lokudla (ml), h 24h inani lokudla kwamanzi, ngisebenza (m) kanye ne-j yemisebenzi yenani lomsebenzi (m / 24h). ). Amagundane agcinwe emazingeni okushisa abonisiwe amahora angama-48. Idatha eboniswe ngo-24, 26, 28 no-30 ° C Bheka Kubhekisela emahoreni angama-24 edlule womjikelezo ngamunye. Amagundane ahlala esondliwe kulo lonke ucwaningo. Ukubaluleka kwezibalo kwahlolwa ngezilinganiso eziphindaphindwayo ze-ANOVA eyodwa ezilandelwa ukuhlolwa kokuqhathanisa okuningi kweTukey. Ama-asterisks akhombisa ukubaluleka kwenani lokuqala le-22 ° C, Umthunzi ukhombisa 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 aphakathi abalwe yonke indawo yokuhlola (amahora angama-0-192). n = 7.
Njengasendabeni yamagundane ajwayelekile ajwayelekile, ee enyuka ngokuqondile ngokuncipha kwamazinga okushisa, futhi kulokhu, ee futhi acishe abe ngu-30% ngaphezulu ngo-22 ° C uma kuqhathaniswa nama-30 ° C (Fig. 2a, b). URer akazange aguquke emazingeni okushisa ahlukahlukene (Fig. 2c, d). Ngokungafani namagundane ajwayelekile wesisindo, ukungena kokudla akuhambelani ne-ee njengomsebenzi wokushisa kwegumbi. Ukudla ukudla, ukudla kwamanzi, kanye neleveli yomsebenzi ngaphandle kokushisa (amakhiwane. 2e-j).
Owesilisa (C57BL / 6J, amasonto angama-20) amagundane e-DIO akhiwe ngawodwana ezindlini ze-metabolic ngo-22 ° C. ngesonto elilodwa ngaphambi kokuqala kwesifundo. Ama-Mice angasebenzisa i-45% HFD Ad Ad Sabitum. Ngemuva kokuvuselelwa kwezinsuku ezimbili, imininingwane eyisisekelo yaqoqwa. Kamuva, izinga lokushisa lakhuliswa ekukhuphukeni kuka-2 ° C njalo ngolunye usuku ngo-06: 00 (ukuqala kwesigaba sokukhanya). Idatha yethulwa njengephutha elijwayelekile ± Iphutha elijwayelekile lokusho, kanye nesigaba esimnyama (18: 00-06: 00 H) kumelwe yibhokisi elimpunga. Ukusetshenziswa kwemali (Kcal / H), Bonke Imali Eness Energy Eness Eats Energy Exerticition emazingeni okushisa ahlukahlukene (kcal / 24 h), c rate yokuvimbela ukushintshanisa (vco2 / vo2: 0.7-1.0), 2 (VCO2 / VO2) (Inani le-zero lichazwa njenge-0.7). E COLELATION Food Ukudla (G), F 24h inani lokudla okuphelele, g 24h inani lamanzi lokudla (ml), h 24h inani lokudla kwamanzi, ngisebenza (m) kanye ne-j yemisebenzi yenani lomsebenzi (m / 24h). ). Amagundane agcinwe emazingeni okushisa abonisiwe amahora angama-48. Idatha eboniswe ngo-24, 26, 28 no-30 ° C Bheka Kubhekisela emahoreni angama-24 edlule womjikelezo ngamunye. Amagundane agcinwe ku-45% hfd kuze kube sekupheleni kwesifundo. Ukubaluleka kwezibalo kwahlolwa ngezilinganiso eziphindaphindwayo ze-ANOVA eyodwa ezilandelwa ukuhlolwa kokuqhathanisa okuningi kweTukey. Ama-asterisks akhombisa ukubaluleka kwenani lokuqala le-22 ° C, Umthunzi ukhombisa 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 0,05, *** р 0,001, **** р nd <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 0,05, *** р 0,001, **** р nd <0,0001. * P <0.05, *** P <0.001, **** P <0.0001.Amanani aphakathi abalwe yonke indawo yokuhlola (amahora angama-0-192). n = 7.
Kokunye uchungechunge lwezivivinyo, sahlola umphumela wokushisa okukhona kumapharamitha afanayo, kodwa kulokhu phakathi kwamaqembu amagundane ahlala agcinwa emazingeni okushisa athile. Amagundane ahlukaniswe ngamaqembu amane anciphise izinguquko zezibalo ngokuphambuka kwesisindo somzimba, amanoni, nesisindo somzimba esijwayelekile (Umdwebo ojwayelekile (Fig. 3a-C). Ngemuva kwezinsuku eziyi-7 zokuqaqanjelwa kwezinsuku eziyi-4,5 ze-EE kwaqoshwa. I-EE Ithinteka kakhulu ekushiseni okukhona Kokubili ngesikhathi samahora asemini nasebusuku (Fig. 3D), futhi kwandise ngokuqondile njengoba izinga lokushisa lincipha kusukela ngo-27,5 ° C kuya ku-22 ° C (Fig. 3e). Uma kuqhathaniswa namanye amaqembu, i-RER yeqembu le-25 ° C lalincishisiwe, futhi kwakungekho umehluko phakathi kwamaqembu asele (Fig. 3f, g). Ukudla ukudla okufana ne-EE iphethini kukhuphuke cishe ngama-30% ku-22 ° C kuqhathaniswa no-30 ° C (Fig. 3h, i). Ukusetshenziswa kwamanzi namazinga omsebenzi awazange ahluke kakhulu phakathi kwamaqembu (Fig. 3J, k). Ukuchayeka kumazinga okushisa ahlukene izinsuku ezingafika kwezingama-33 akuzange kuholele umehluko esisindo somzimba, isisindo se-lean, kanye ne-fat mass phakathi kwamaqembu (kuphela ama-3n Izikolo ezenzelwe ukuzibika (Fig. 3n-s). 3b, r, c)) and the fat mass increased by more than 2 times (from ~1 g to 2–3 g, Fig. 3c, t, c). Ngeshwa, iKhabinethi le-30 ° C linamaphutha wokulinganisa futhi alikwazi ukuhlinzeka nge-EE enembile nedatha ye-RER.
- Isisindo somzimba (a), isisindo se-lean (b) kanye ne-fat mass (c) ngemuva kwezinsuku eziyi-8 (ngolunye usuku ngaphambi kokudlulisela ohlelweni lwe-luble). Ukusetshenziswa kwamandla d (kcal / h). Ukusetshenziswa kwamandla okuphakathi (amahora angama-0-108) emazingeni okushisa ahlukahlukene (ama-Kcal / ama-24 amahora). f ratio Repiratory Exchange Ratio (RER) (VCO2 / VO2). g kusho ukuthi i-RER (VCO2 / VO2). h okuphelele kokudla (g). Ngiqonde ukudla okudlayo (G / 24 amahora). j Ukusetshenziswa kwamanzi okuphelele (ml). Ukusetshenziswa kwamanzi okujwayelekile (ml / 24 h). l Izinga lomsebenzi wokuqongelela (m). Ileveli yomsebenzi wesilinganiso (m / 24 h). n isisindo somzimba ngosuku lwe-18, o Ushintsho ku-Weight Weight (kusuka -8th kuya ku-18 usuku olungu-18), q ushintshele ku-Lean Mass (kusuka-ku-18 kufinyelela ngosuku lwe-18), , futhi ushintshe isisindo esinamafutha (kusuka ezinsukwini eziyi-18 kuye kwezingu-18). Ukubaluleka kwezibalo kwezinyathelo eziphindaphindwayo kwavivinywa yi-Oneway-Anova elandelwa ukuhlolwa kokuqhathanisa okuningi kweTukey. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001. * P <0,05, ** P <0,01, *** p <0,001, **** P <0,0001. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001. * P <0,05, ** P <0,01, *** p <0,001, **** P <0,0001. * P <0.05, ** P <0.01, *** p <0.001, ****1 p <0.0001.Idatha yethulwa njengoba kusho ukuthi: Iphutha elijwayelekile lokusho, isigaba esimnyama (18: 00-06: 00 H) simelelwa amabhokisi ampunga. Amachashazi kuma-histograms amelela amagundane ngamanye. Amanani aphakathi abalwa kuyo yonke isikhathi sokuhlola (amahora angama-0-108). n = 7.
Amagundane afaniswe nesisindo somzimba, isisindo esinciphile, futhi isisindo esinamafutha esisekelweni (amakhiwane. 4a. 4a. ' . Lapho uqhathanisa amaqembu amagundane, ubudlelwano phakathi kwe-ee kanye lokushisa bubonisa ubudlelwano obufanayo obunokushisa ngokuhamba kwesikhathi kubumbi obufanayo. Ngakho-ke, amagundane agcinwe ngo-22 ° C adliwe amandla acishe abe ngu-30% ngaphezu kwamagundane agcinwe ngo-30 ° C (Fig. 4D, e). Lapho utadisha imiphumela ezilwaneni, izinga lokushisa lalingahlali lithinta njalo i-RER (Fig. 4f, g). Ukudla ukudla, ukuthathwa kwamanzi, kanye nomsebenzi bekungathinteki kakhulu izinga lokushisa (amakhiwane. 4h-m). Ngemuva kwezinsuku ezingama-33 zokukhulisa, amagundane angu-30 ° C wayenesisindo esiphakeme kakhulu somzimba kunamagundane ngo-22 ° C (Fig. 4n). Uma kuqhathaniswa namaphoyinti avuselelayo abukeli, amagundane akhuliswa ngo-30 ° CE kwakungamagundane aphezulu kakhulu ngaphezu kwamagundane akhuliswe ngo-22 ° C (asho ± iphutha elijwayelekile lokushiwo: Fig. 4o). Isisindo esiphakeme kakhulu sasibangelwa ukwanda kwesisindo esinamafutha (umdwebo 4p, q) kunokuba kukhuphuke isisindo se-Lean (Fig. 4r, s). Kuyahambisana nenani eliphansi le-eE ku-30 ° C, ukuvezwa kofuzo oluningi lwe-bat olukhulisa ukusebenza kwe-bat / umsebenzi kwancishiswa ngo-30 ° C: Adra1a, adrb3, ne-PRDM16. Ezinye izakhi zofuzo ezisemqoka futhi ezikhulisa umsebenzi we-bat / umsebenzi ezingathintekanga Ngokumangazayo, i-UCP1 ne-Vegf-a, ehambisana nomsebenzi owengeziwe we-thermogenic, ayincipha eqenjini le-30 ° C. Eqinisweni, amazinga e-UCP1 emagungeni amathathu ayephakeme kuneqembu lama-22 ° C, ne-Vegf-A kanye ne-ADRB2 kakhulu. Uma kuqhathaniswa neqembu lama-22 ° C, amagundane agcinwe ngo-25 ° C no-27,5 °
- Isisindo somzimba (a), isisindo se-lean (b) kanye ne-fat mass (c) ngemuva kwezinsuku eziyi-9 (ngolunye usuku ngaphambi kokudlulisela ohlelweni lwe-luble). Ukusetshenziswa kwamandla d (ee, kcal / h). Ukusetshenziswa kwamandla okujwayelekile (amahora angama-0-96) emazingeni okushisa ahlukahlukene (ama-kcal / amahora angama-24). f isilinganiso sokushintshaniswa kokuphefumula (Rer, vco2 / VO2). g kusho ukuthi i-Rer (vco2 / VO2). h okuphelele kokudla (g). Ngiqonde ukudla okudlayo (G / 24 amahora). j Ukusetshenziswa kwamanzi okuphelele (ml). Ukusetshenziswa kwamanzi okujwayelekile (ml / 24 h). l Izinga lomsebenzi wokuqongelela (m). Ileveli yomsebenzi wesilinganiso (m / 24 h). n isisindo somzimba ngosuku 23 (g), o Ukushintsha kwesisindo somzimba, i-q leans, Q Mass (G) kuqhathaniswa nosuku lwe-8, usuku 23 kuqhathaniswa nosuku lwe -8. Ukubaluleka kwezibalo kwezinyathelo eziphindaphindwayo kwavivinywa yi-Oneway-Anova elandelwa ukuhlolwa kokuqhathanisa okuningi kweTukey. * P <0.05, *** P <0.001, **** P <0.0001. * P <0.05, *** P <0.001, **** P <0.0001. * Р <0 0,05, *** р 0,001, **** р nd <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 0,05, *** р 0,001, **** р nd <0,0001. * P <0.05, *** P <0.001, **** P <0.0001.Idatha yethulwa njengoba kusho ukuthi: Iphutha elijwayelekile lokusho, isigaba esimnyama (18: 00-06: 00 H) simelelwa amabhokisi ampunga. Amachashazi kuma-histograms amelela amagundane ngamanye. Amanani asho ukuthi azobalwa yonke isikhathi sokuhlola (amahora angama-0-96). n = 7.
Njengabantu, amagundane ajwayele ukudala ama-microenvironments ukunciphisa ukulahleka kokushisa emvelweni. Ukunciphisa ukubaluleka kwale ndawo nge-eE, sahlola i-22, 25, 27.5, no-30 ° C, onogada besikhumba noma ngaphandle kwezikhumba. Ku-22 ° C, ukungezwa kwezikhumba ezijwayelekile kunciphisa i-ee cishe ngo-4%. Isengezo esilandelayo sezinto ezidlwengula zinciphise i-EE ngo-3-4% (Fig. 5a, b). Azikho izinguquko ezibalulekile ezi-RER, ukudla ukudla, ukudla kwamanzi, noma amazinga omsebenzi abonwa ngokungeziwe kwezindlu noma izikhumba + zombhede (Umdwebo we-5i-P). Ukungezwa kwezinto ezidliwayo zesikhumba nezidleke nakho kuncishiswe kakhulu i-EE ngo-25 no-30 ° C, kepha izimpendulo zincanyana. Ngo-27.5 ° C akukho mehluko owabonwa. Ngokuphawulekile, kulezi zivivinyo, i-ee yancipha ngokunwebeka okushisa, kuleli cala cishe ama-57% aphansi kune-30 ° C uma kuqhathaniswa no-22 ° C (Fig. 5c-H). Ukuhlaziywa okufanayo kwenziwa kuphela esigabeni esikhanyayo, lapho i-EE yayisondelene nezinga le-basal metabolic, ngoba amagundane aphumule kakhulu esikhunjeni, okuholela ekulinganiseni amasayizi ahlukene emazingeni okushisa ahlukene (umkhiwane owengeziwe. 2a-H) .
Idatha yamagundane endaweni yokukhosela kanye nezinto ezidliwayo (eziluhlaza okwesibhakabhaka), ikhaya kodwa akukho maticeiting (eluhlaza okwesibhakabhaka), kanye ne-Home and Nest Material (orange). Ukusetshenziswa kwamandla (ee, kcal / h) amakamelo a, c, e kanye g ngo-22, 25, 27.5 no-30 ° C, B, D, F kanye ne-H kusho i-EE (KCAL / H). Idatha ye-IP yamagundane ifakwe ku-22 ° C: I Izinga lokuphefumula (RER, VCO2 / VO2), j/7 / vo2), g / 24 h), m Inani lokuphuza amanzi (ml), n averoid average amanzi auc (ML / 24h), o Umsebenzi ophelele (m), izinga lomsebenzi we-P (M / 24h). Idatha yethulwa njengoba kusho ukuthi: Iphutha elijwayelekile lokusho, isigaba esimnyama (18: 00-06: 00 H) simelelwa amabhokisi ampunga. Amachashazi kuma-histograms amelela amagundane ngamanye. Ukubaluleka kwezibalo kwezinyathelo eziphindaphindwayo kwavivinywa yi-Oneway-Anova elandelwa ukuhlolwa kokuqhathanisa okuningi kweTukey. * 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 aphakathi abalwe yonke indawo yokuhlola (amahora angama-0-72). n = 7.
In normal weight mice (2-3 hours of fasting), rearing at different temperatures did not result in significant differences in plasma concentrations of TG, 3-HB, cholesterol, ALT, and AST, but HDL as a function of temperature. Umdwebo 6a-e). Ukugxila kwezindawo zokudla kwe-leptin, i-insulin, i-c-peptide, ne-glucagon futhi akubanga ukwehluka phakathi kwamaqembu (izibalo 6g-J). Ngosuku lokuhlolwa kwe-glucose ukubekezelela (ngemuva kwezinsuku ezingama-30 emazingeni okushisa ahlukahlukene), izinga lama-glucose eliyisisekelo (amahora angama-5-6 wokuzila ukudla) lalicishe libe ngu-6.5 mm, ngaphandle komehluko phakathi kwamaqembu. Ukuphathwa kwe-glucose yomlomo kukhuphuke kakhulu ukugxila kwe-glucose kuwo wonke amaqembu, kepha zombili indawo ephakeme kanye nendawo ekhuphukayo ngaphansi kwe-curves (IAUCS) (15-10 min) yayiphansi eqenjini lamagundane akhiwe ngo-30 ° C (amaphuzu wesikhathi ngasinye: P <0.05-P <0.0001, Fig. 6k, l) Uma kuqhathaniswa namagundane ahlalwe ngo-22, 25 no-27,5 okunye). Ukuphathwa kwe-glucose yomlomo kukhuphuke kakhulu ukugxila kwe-glucose kuwo wonke amaqembu, kepha zombili indawo ephakeme kanye nendawo ekhuphukayo ngaphansi kwe-curves (IAUCS) (15-10 min) yayiphansi eqenjini lamagundane akhiwe ngo-30 ° C (amaphuzu wesikhathi ngasinye: P <0.05-P <0.0001, Fig. 6k, l) uma kuqhathaniswa namagundane ahlalwe ngo-22, 25 no-27,5 okunye). Гююич н нр гцице нровиюх Коведентा лькок Пон In the, та кон и крищендь приымая гыы-1 (Отде ленные вреченые точкеые ". Ukuphathwa ngomlomo kwe-glucose kukhuphuke kakhulu ukugxila kwe-glucose kuwo wonke amaqembu, kepha zombili indawo ephezulu kanye nendawo ekhuphukayo ngaphansi kwamajika (i-15-120 min) kwakuphansi eqenjini lama-30 ° C P <0.0001, Fig. 6k, l) uma kuqhathaniswa amagundane agcinwe ngo-22, 25 no-27.5 ° C (okwakungafani komunye nomunye).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, 峰值浓度和曲线下增加面积 (IAUC) (15-120 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 和 27.5 ° C 的小鼠 (彼此之间没有差异) 相比.口服 葡萄糖 的 给给 药 了 所有组 血糖 浓度 在 在 在 在 在 小鼠组 小鼠组 中, 浓度浓度点 点: p <0.05-P < I-0.0001, 图 6k, L) 与饲养在 22,25 和 27.5 ° C 的小鼠 (彼此之间没有差异) 相比.Ukuphathwa ngomlomo kwe-glucose kukhuphuke kakhulu ukugxila kwe-glucose kuwo wonke amaqembu, kepha zombili izingodo nendawo ngaphansi kwejika (IAUC) (15-120 min) zaziphansi eqenjini lama-30 ° C-Fed Mice (wonke amaphuzu).: P <0,05-p <0,0001, bheka. : P <0.05-p <0.0001, Fig.6l, l) Uma kuqhathaniswa namagundane agcinwe ngo-22, 25 no-27.5 ° C (akukho mehluko kusuka komunye nomunye).
Ukugxila kwe-plasma ye-TG, 3-HB, i-Cholesterol, HDL, ALT, AST, FFA, i-glukhalin, i-c-peptide ngemuva kwezinsuku ezingama-33 zokudla . Amagundane awazange aphindliwa amahora angama-2-3 ngaphambi kokusampula kwegazi. Okuhlukile kwakuwuvivinyo lwe-glucose olungabekezeleli, olwenziwe ezinsukwini ezimbili ngaphambi kokuphela kwesifundo kumagundane asheshe asheshe amahora angama-5-6 futhi agcinwe emazingeni okushisa afanele izinsuku ezingama-31. Amagundane aphonswa inselelo ngesisindo somzimba esingu-2 g / kg. Indawo engaphansi kwe-curve data (L) ivezwa njengedatha ekhuphukayo (IAUC). Idatha yethulwa njenge-adve ± SEM. Amachashazi amelela amasampula athile. * 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, **** 1, ** = 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, **** 1, ** = 7. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001, n = 7.
E-Dio Mice (futhi isheshe isheshe ishele amahora angama-2-3), i-cholesterol ye-plasma, i-HDL, i-Alt, AST, kanye ne-FFA ukugxila bekungafani phakathi kwamaqembu. Bobabili i-TG ne-Glycerol baphakanyiswa kakhulu eqenjini le-30 ° C ngokuqhathaniswa neqembu lama-22 ° C (amanani 7A-H). Ngokuphambene, 3-GB yayicishe ibe ngama-25% aphansi ngo-30 ° C ngokuqhathaniswa no-22 ° C (Umdwebo 7b). Ngakho-ke, yize amagundane egcinwe ku-22 ° C enza ukulinganisela kwamandla okuhle, njengoba kuphakanyiswe ngokuzungeza isisindo, umehluko wokugxila kwe-plasma ye-TG, i-Glycerol, futhi amacembe angu-22 ° C lapho amasampula ayengaphansi kuka-22 ° C. ° C. Amagundane akhuliswa ngo-30 ° C ayesesimweni esingesihle ngokwengeziwe. Kuyahambisana nalokhu, ukugxila kwesibindi kwe-glycerol ne-TG, kodwa hhayi i-glycogen ne-cholesterol, bekuphakeme eqenjini le-30 ° C (i-Fig angemuva. 3a. 3a-D). Ukuphenya ukuthi ngabe umehluko wokuncika kokushisa e-lipolysis (njengoba ulinganiswe yi-plasma tg ne-glycerol) kungumphumela wezinguquko zangaphakathi kuma-epididemal noma amafutha e-adipose kulezi zitolo ekugcineni kocwaningo kanye no-fatty acid ex ekugcineni Vivo. nokukhishwa kwe-glycerol. Kuwo wonke amaqembu okuhlola, amasampula wezicubu ze-adipose kusuka kuma-epididemal kanye namadepho e-ingunal abonise okungenani ukwanda okubili okubili ku-glycerol kanye ne-FFA ukukhiqizwa ekuphenduleni ukukhuthaza kwe-isoproterenol (umkhiwane owengeziwe. 4A. 4A-D). Kodwa-ke, awukho umphumela wokushisa kwegobolondo ku-basal noma i-liporerenol-avuselelwe i-lipolysis yatholakala. Ngokuhambisana nesisindo somzimba esiphakeme kanye nesisindo samafutha, amazinga we-plasma leptin ayephakeme kakhulu eqenjini le-30 ° C kuneqembu lama-22 ° C (Umdwebo 7i). Ngokuphambene nalokho, amazinga we-plasma we-insulin kanye ne-c-peptide azange ahluka phakathi kwamaqembu okushisa (umdwebo 7k, k), kepha kuleli purucagon akhombisa ukuncika kokushisa, kepha kulokhu cishe ama-22 ° C eqenjini eliphambene aqhathaniswa kabili kuya ku-30 ° C. Kusuka. Iqembu C (Fig. 7l). I-FGF21 ayizange ihluke phakathi kwamaqembu okushisa ahlukene (Fig. 7m). Ngosuku lwe-OGTT, isisekelo se-glucose segazi sasicishe kube ngu-10 mm futhi sasingafani phakathi kwamagundane afakwe emazingeni okushisa ahlukene (Fig. 7n). Ukuphathwa ngomlomo kwe-glucose kwandise amazinga kashukela wegazi futhi kufakwe kuwo wonke amaqembu lapho kufinyelela imizuzu engaba ngu-18 mm 15 ngemuva kokuthatha. Kwakungekho umehluko obalulekile ku-IAUC (15-120 min) nokugxila ngesikhathi esihlukile samaphuzu aphansi (15, 30, 60, 90 no-120 min) (Umdwebo 7n, o).
Ukugxila kwe-plasma ye-TG, 3-HB, i-Cholesterol, HDL, ALT, AST, FFA, i-FFA, i-FGF21 kuboniswe egunjini labesilisa abadala (AO) amagundane ngemuva kwezinsuku ezingama-33 zokondla. izinga lokushisa elithile. Amagundane awazange aphindliwa amahora angama-2-3 ngaphambi kokusampula kwegazi. Uvivinyo lokubekezelelana lwe-glucose lwe-glucose lwaluhlukile njengoba lwenziwa ngomthamo we-2 g / kg isisindo somzimba ezinsukwini ezimbili ngaphambi kokuphela kokufunda amagundane asheshe asheshe asheshe amagundane izinsuku ezingama-31. Le ndawo ngaphansi kwe-Curve Idatha (o) ikhonjiswa njengedatha ekhulayo (iAUC). Idatha yethulwa njenge-adve ± SEM. Amachashazi amelela amasampula athile. * 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, **** 1, ** = 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, **** 1, ** = 7. * P <0.05, ** P <0.01, ** P <0.001, **** p <0.0001, n = 7.
Ukudluliswa kwedatha ye-rodent kubantu kuyinkinga eyinkimbinkimbi edlala indima enkulu ekuhumusheni ukubaluleka kokubonwayo ngokomongo wocwaningo lwezomzimba nolomkhemisi. Ngenxa yezizathu zezomnotho kanye nokwenza lula ucwaningo, amagundane avame ukugcinwa emazingeni okushisa asekamelweni ngaphansi kwendawo yawo ye-thermoneutral, okuholela ekusebenzeni kwezinhlelo ezahlukahlukene zokunxenxa okukhokhela amanani e-metabolic futhi angahle akhiphe ukuhumusha9. Ngakho-ke, ukuvezwa kwamagundane kuya kubanda kungahle kunikeze amagundane amelana nokukhuluphala okubangelwa kokudla futhi kungavimbela i-hyperglycemia ngamagundane aphathiswe ama-streptozotocin ngenxa yokwenyuka kwe-glucose ezokuhamba okungeyona eye-insulin. Kodwa-ke, akucaci ukuthi ukuvezwa isikhathi eside ukubhekana namazinga okushisa ahlukahlukene afanele (kusuka egumbini kuya ku-thermoneUTRARR) kuthinta i-homeostasis ehlukile yamandla e-homeostasis evamile yamagundane (ekudleni) kanye nama-dio mice (ku-HFD) kanye ne-metabolic, kanye nezinga lapho bekwazile ukulinganisa ukwanda kwe-ee ngokwanda kokudla kokudla. Ucwaningo olwethulwe kule ndatshana luhlose ukucacisa lesi sihloko.
Sibonisa ukuthi kumagundane ajwayelekile asezingeni elijwayelekile kanye namagundane amaduna ajwayelekile, ahlobene kakhulu nokushisa kwegumbi phakathi kuka-22 no-30 ° C. Ngakho-ke, i-22 ° C yayingama-30% aphakeme kunakwa-30 ° C. kuwo womabili amamodeli wegundane. Kodwa-ke, umehluko obalulekile phakathi kwamagundane ajwayelekile we-mice kanye ne-dio mice ukuthi ngenkathi amagundane ajwayelekile ahambisana namazinga okushisa aphansi ngokulungisa imali yokudla ngokufanele, ukudla kwe-dio amagundane ahlukahlukene. Izinga lokushisa lesifundo lalifana. Ngemuva kwenyanga eyodwa, amagundane e-DIO agcinwe ngo-30 ° C athola isisindo somzimba esiningi nesisindo samafutha kunamagundane agcinwe ngo-22 ° C, kanti abantu abajwayelekile bagcinwe emazingeni okushisa afanayo futhi isikhathi esifanayo abaholele emkhuhlane. umehluko othembekile esisindo somzimba. isisindo amagundane. Uma kuqhathaniswa namazinga okushisa aseduze kwe-thermoneUTRAL noma ekushiseni kwamakamelo, ukukhula emafulethweni ekamelweni kuholele ekudleni okuthe xaxa kokudla okunamafutha aphezulu kodwa hhayi ekudleni kwegundane okujwayelekile ukuze uthole isisindo esingaphansi. umzimba. Isekelwa ezinye izifundo17,18,19,20,21 kodwa hhayi ngo-All22,23.
Amandla wokwenza i-microenviromment ukunciphisa ukulahleka kokushisa kudidekile ukuguqula ukungathathi hlangothi kwesobunxele kwesokunxele8, 12. Esifundweni sethu, ukucashunwa kwesidleke nokucashunwa kuncishisiwe kuze kube ngu-28 ° C. Ngakho-ke, imininingwane yethu ayisekeli ukuthi iphuzu eliphansi le-thermoneutrality lingamagundane amadala okukodwa, noma ngaphandle kokucebisezelwa imvelo, kufanele kube ngu-26-28 ° C njengoba kukhonjisiwe8,12, kepha kuyasekela ezinye izifundo ezibonisa i-thermonetrality. amazinga okushisa angu-30 ° C e-Low Poice Mice7, 10, 24. Ukuhlanganisa izindaba, iphoyinti le-thermoneUTral eMice likhonjiswe ukuthi lingabi tuli phakathi nosuku njengoba liphansi ngesikhathi sekhalori (ngokukhanya), mhlawumbe ngenxa yekhalori ephansi ukukhiqizwa ngenxa yomsebenzi kanye ne-thermogenesis yokudla. Ngakho-ke, esigabeni esikhanyayo, iphuzu eliphansi lokungathathi hlangothi kwe-thermal liphenduka libe ~ 29 ° ° с, nasesigabeni esimnyama, ~ 33 ° с 125.
Ekugcineni, ubudlelwano phakathi kokushisa okukhona kanye nokusetshenziswa kwamandla okuphelele kunqunywa ngokushisa kokushisa. Kulesi simo, isilinganiso sendawo engaphezulu kwevolumu yisibonakaliso esibalulekile sokuzwela okushisayo, okuthinta womabili lakusasa lokushisa (indawo engaphezulu) kanye nesizukulwane sokushisa (ivolumu). Ngaphezu kwendawo engaphezulu, ukudluliswa kokushisa kunqunywa ngokufakwa (inani lokudluliswa kokushisa). Ebuntwini, isisindo samafutha singanciphisa ukulahleka kokushisa ngokwakha umqobo wokufakelwa phansi ezungeze igobolondo lomzimba, futhi kuphakanyiswe ukuthi ama-Fat Mass abalulekile ekufakweni kwegundane, anciphise iphuzu lokushisa eliphansi kanye nokunciphisa ukuzwela okuphansi ngaphansi kwe-thermal neutral ( ijika emthambekeni). Ukushisa okulinganiselwe ngokuqhathaniswa ne-12. Isifundo sethu asizangelwanga ukubheka ngqo lolu budlelwano bokubeka ngoba idatha yokwakheka komzimba iqoqwe izinsuku eziyi-9 ngaphambi kokuqoqwa kwemali yokusetshenziswa kwamandla futhi ngoba isisindo samafutha besingazinzile kulolu cwaningo. Kodwa-ke, njengoba amagundane ajwayelekile kanye ne-dio mice ane-30% ephansi ee ngo-30 ° C kuno-22 ° C naphezu kokungenamkhawulo okungama-5 kuMass Mass, imininingwane yethu ayisekeli ukuthi ukukhuluphala kufanele kunikeze ukufakwa okuyisisekelo. isici, okungenani hhayi ebangeni lokushisa eliphenya. Lokhu kuhambisana nezinye izifundo zenzelwe kangcono ukuhlola le4,24. Kulezi zifundo, umphumela wokufakelwa kokukhuluphala wawumncane, kepha uboya batholakale behlinzeka ngo-30-50% wokufakelwa okuphelele kwe-thermal4,24. Kodwa-ke, egunjini elifile, ukuhanjiswa okushisayo kukhuphuke cishe ngama-450% ngokushesha ngemuva kokufa, kuphakamisa ukuthi umphumela wokufaka oboya uyadingeka ezihlathini zoboya, kufaka phakathi i-vasoconstrictions, ukusebenza. Ngaphezu kokuhlukahluka kwezinhlobo zoboya obuphakathi kwamagundane nabantu, umphumela ompofu wokufakelwa kokukhuluphala amagundane nawo ungathonywa ukucatshangelwa okulandelayo: Into efaka amafutha yamafutha abantu ilawulwa yi-subcutaneous fat mass (ubukhulu) 26,27. Imvamisa kuma-rodents angaphansi kwama-20% wesilwane esiphelele samafutha28. Ngaphezu kwalokho, i-Total Fat Mass kungenzeka ingabi yisilinganiso se-sunoptimal sokufakelwa okushisayo komuntu, njengoba kuvezwe ukuthi ukufakwa okuthuthukile okushisayo kususwe ukwenyuka okungenakugwenywa endaweni engaphezulu (ngakho-ke kwandise ukulahleka kokushisa) njengoba kukhuphuka amafutha. .
Kumagundane ajwayelekile, ukugxila kwe-plasma okusheshayo kwe-TG, 3-HB, i-cholesterol, i-HDL, i-ALT, no-AST abashintshanga emazingeni okushisa ahlukene cishe amasonto angu-5. babefana ngesisindo nokwakheka komzimba njengasekupheleni kwesifundo. Ngokuhambisana nokufana kwesisindo esinamafutha, futhi kwakungekho umehluko kumazinga we-plasma leptin, noma ekuzilandeni i-insulin, c-peptide, ne-glucagon. Kutholakale amasiginali amaningi e-Dio Mice. Yize amagundane angu-22 ° C nawo awanayo ibhalansi yamandla engemihle kulesi simo (njengoba athole isisindo), ekugcineni kwesifundo) ayengamandla amaningi angenawo amandla aqhathaniswa namasu akhuliswa ngo-30 ° C, ngezimo ezifana ama-ketones aphezulu. Ukukhiqizwa ngumzimba (3-GB) nokwehla kokuqothuka kwe-glycerol ne-TG kwi-plasma. Kodwa-ke, umehluko othembele wokushisa ku-lipolysis awubonakali waba ngumphumela wezinguquko ezinkulu ku-epidedymal noma amanoni e-lusinal, njenge-FFA ne-glycerol ekhishwe kumafutha akhishwe kulezi zinga lokushisa amaqembu ayafana. Yize sasingaphenyi izwi elinozwela esifundweni samanje, abanye bathole ukuthi (kususelwa ekulinganisweni kwenhliziyo futhi kusho ukucindezela kwenhliziyo) kuhlobene ne-30 ° C 20% C Ngakho-ke, umehluko othembele wokushisa esikhathini sokuzwela ungadlala indima eLipolysis ocwaningweni lwethu, kodwa selokhu kwanda ithoni enozwela kuvusa ama-lipolysis, ezinye izindlela zingamelana nalokhu kuncipha kulokhu amagundane amasiko. Iqhaza elingaba khona ekuqhekekeni kwamafutha omzimba. Lokushisa kwegumbi. Ngaphezu kwalokho, ingxenye yomphumela wokuvuselela ithoni enozwela ku-lipolysis ngokungaqondile ngokuvinjwa okuqinile kokuphazamiseka kwe-insulin, kodwa esifundweni sethu, i-insulin yethu yokudla, ithoni enozwela enozwela emazingeni okushisa e-C-peptide emazingeni okushisa ahlukahlukene akwanele ukuguqula i-lipolysis. Esikhundleni salokho, sathola ukuthi umehluko ngesimo samandla kungenzeka kakhulu kunomthelela omkhulu kulolo mehluko egunjini le-DIO. Izizathu eziyisisekelo eziholela ekuqondisweni okungcono kokudla okune-ee kuma-mince ajwayelekile adinga ukutadisha okwengeziwe. Ngokuvamile, noma kunjalo, ukungena kokudla kulawulwa yi-Homeoustatic and heedonic cues31,32,33. Yize kunenkulumompikiswano yokuthi yiziphi kulezi zimpawu ezimbili ezibaluleke kakhulu, 31,32,33 kwaziwa kakhulu ukuthi ukusetshenziswa kwesikhathi eside kokudla okunamafutha amaningi kuholela ekuziphatheni okudla okunenjabulo okuholela ezingeni elithile elihlobene nalo I-Homeostasis. . - Ukulawulwa kokudla Intake34,35,36. Ngakho-ke, ukukhuphuka kokudla kwe-hedonic kwe-DIO Mice ephethwe nge-45% HFD kungaba ngesinye sezizathu zokuthi kungani amagundane alimale ukudla nge-ee. Kuyathakazelisa ukuthi, umehluko ekuzindeni kanye nama-hormone alawulwa yigazi - nawo agcinwe egunjini elilawulwa amazinga okushisa, kepha hhayi amagundane ajwayelekile. E-Dio Mice, amazinga we-plasma leptin akhuphuke ngokushisa namazinga we-glucagon anciphile ngamazinga okushisa. Izinga lapho izinga lokushisa lingathonya ngokuqondile ukuthi lolu umelo wokushisa lufanelwe ukuqhubeka kokufunda, kepha endabeni ye-leptin, i-arvice elibi kakhulu futhi ngaleyo ndlela isisindo samafutha aphansi egunjini ngo-22 ° C sadlala indima ebalulekile, njengoba isisindo esinamafutha ne-plasma leptin ixhumeke kakhulu37. Kodwa-ke, ukutolika kwesiginali ye-grucagon kuyamangaza ngokwengeziwe. Njengase-Insulin, imfihlo ye-glucagon yavinjelwa ngokuqinile ukwanda kwethoni yozwela, kepha kwabikezelwa ukuthi ithoni eliphakeme kakhulu elinozwela kwabikezelwa ukuba seqenjini lama-22 ° C, elalinokugxila okuphezulu kakhulu kwe-plasma glucagon. I-insulin ngomunye umlawuli oqinile we-plasma glucagon, kanye nokumelana kwe-insulin kanye nesifo sikashukela sohlobo 2 kuhlotshaniswa ngokuqinile nokuzila ukudla kanye ne-hyprandial hyperglucagonmia 38,39. Kodwa-ke, amagundane e-DIO esifundweni sethu nawo ayengazwela, ngakho-ke futhi lokhu akunakuba yinto eyinhloko ekwandeni kwe-grucagon ukusayina eqenjini lama-22 ° C. Okuqukethwe kwamafutha wesibindi kuhlotshaniswa kahle nokwanda kwe-plasma glucagon okuhlushwayo, izindlela zazo, zinciphise ukukhiqizwa kwe-amino acid, futhi kwandise ukujikeleza kwe-amino acid, kwakhulisa i-Amino acid-glucagon-stured freeion40,41, 42. Kodwa-ke, njengoba ukugxila okukhishwe kwe-Glycerol ne-TG akuzange kuhluke phakathi kwamaqembu okushisa esifundweni sethu, lokhu futhi akunakuba yinto engaba khona ekwandeni kokugxila kwe-plasma eqenjini lama-22 ° C. I-TriodoToThyronine (T3) idlala indima ebalulekile ezindaweni ezijwayelekile ze-metabolic kanye nokuqalwa kokuzivikela kwe-metabolic ngokumelene ne-hypothermia43,44. Ngakho-ke, i-plasma t3 ukugxila, mhlawumbe okulawulwa yizinqubo ezilungisiwe eziphakathi nendawo, amagundane angama-45,46 kuwo womabili izimo ze-bhermoneutral47, yize ukwanda kwabantu kuncane, okucatshangwa kakhulu kumagundane. Lokhu kuyahambisana nokulahleka kokushisa emvelweni. Asikalanga ukugxila kwe-plasma t3 esifundweni samanje, kodwa kungenzeka ukuthi kungenzeka ukuthi kusaphansi eqenjini le-30 ° C, elingachaza umphumela waleli qembu kumazinga we-Plasma Glucagon, njengoba nathi (Simfanekiso sivuselelekile 5a) nabanye I-T3 ikhulisa i-Plasma Glucain ngendlela ethembele umthamo. Ama-hormone e-thyroid abikwe ukuthi angezwa inkulumo ye-FGF21 esibindini. Njenge-glucagon, ukugxila kwe-plasma fgf21 kukhuphuke kakhulu nge-plasma t3 ukugxila (i-Fig are-5b. Izizathu eziyisisekelo zokungafani nalokhu kudotshwa kwe-FGFF21 kutholakale emazingeni aphezulu okuvezwa kwe-T3 ngokuqhathaniswa ne-T3-Gign-5b).
I-HFD ikhonjiswe ukuthi ihlotshaniswe ngokuqinile nokungabekezeleleki kwe-glucose kanye nokumelana kwe-insulin (amamaki) kuma-mice akhuliswe ngo-22 ° C. Kodwa-ke, i-HFD ibingahlotshaniswa nokubekezelelana ne-glucose noma ukumelana kwe-insulin lapho ikhule endaweni ye-thermoneutral (echazwa lapha njengo-28 ° C) 19. Esifundweni sethu, lobu budlelwano abuphindwanga egunjini le-DIO, kodwa amagundane ajwayelekile wesisindo agcinwe ku-30 ° C C ukubekezelela okuthuthuke kakhulu. Isizathu salo mehluko sidinga ukutadisha okwengeziwe, kepha singathonywa iqiniso lokuthi amagundane e-DIO ocwaningweni lwethu ayengamelana nayo i-insulin, ngokudla okuhlangenwe nakho kwe-plasma c-peptide kanye nezikhathi zokugxila kwe-insulin eziyishumi nambili kunesisindo esijwayelekile. nasegazini esiswini esingenalutho. Ukugxila kukashukela okubalelwa ku-10 mm (cishe ama-6 mm ngesisindo somzimba esijwayelekile), okubonakala sengathi kushiya iwindi elincane nganoma yimiphi imiphumela ezuzisayo yokuchayeka ezimweni ze-bhermoneutral ukuze zithuthukise ama-glucose. Into engenzeka edidayo ukuthi, ngenxa yezizathu ezisebenzayo, i-OgTT yenziwa emazingeni okushisa asekamelweni. Ngakho-ke, amagundane agcinwe emazingeni okushisa aphezulu anokwamukelwa okubandayo omnene, okungathinta ukumuncwa kukaGlucose / imvume. Kodwa-ke, ngokuya ngokugxila kwegazi okufanayo kwegazi elifanayo emaqenjini okushisa ahlukene, izinguquko ekushiseni okukhona kungenzeka ukuthi zithinte kakhulu imiphumela.
Njengoba kushiwo ngaphambili, kusanda kuqokonyiswa okukhulisa izinga lokushisa lasekamelweni kungamisa ukusabela okuthile ekucindezelekeni okubandayo, okungase kungabaza ukudluliswa kwedatha yegundane kubantu. Kodwa-ke, akucaci ukuthi yiliphi izinga lokushisa elifanele lokugcina amagundane ukulingisa physiology womuntu. Impendulo yalo mbuzo nayo ingathonywa yinsimu yokufunda kanye nokuphela kokufundwa. Isibonelo salokhu umphumela wokudla ku-Siler Foot Ukuqongelela, ukubekezelela ushukela kanye nokumelana ne-insulin19. Mayelana nokusetshenziswa kwemali kwamandla, abanye abacwaningi bakholelwa ukuthi i-thermoneUTRAlity iyindlela enhle yokukhulisa, njengoba abantu bedinga amandla amancane okugcina amagundane omzimba asemqoka, futhi bachaza izinga lokushisa elilodwa lamagundane asemqoka njengama-30 ° C7,10. Abanye abacwaningi bakholelwa ukuthi izinga lokushisa liqhathaniswa nalolo bantu livame ukuzwa ngamagundane asebekhulile ngedolo elilodwa ngu-23-25 ° C, njengoba bathola i-thermoneutrality ukuze babe ngu-26-28 ° C futhi ngokusekelwe kubantu bephansi cishe ngo-3 ° C. Izinga lokushisa labo elibucayi eliphansi, elichazwa lapha njengo-23 ° C, lincane 8.12. Isifundo sethu siyahambisana nezinye izifundo ezisho ukuthi ukungathathi hlangothi kwe-thermal akutholakali ku-26-28 ° C4, 7, 10, 11, 24, 25, kukhombisa ukuthi kuphansi kakhulu. Enye into ebalulekile okufanele icatshangelwe maqondana nokushisa kwegumbi kanye nokushisa kwe-thermoneTrality egunjini kuyinto eyodwa noma yeqembu. Lapho amagundane egcinwe ngamaqembu esikhundleni ngawodwana, njengoba esifundweni sethu, ukuzwela okushisa kwancishiswa, mhlawumbe kungenxa yokuqunjelwa kwezilwane. Kodwa-ke, izinga lokushisa lasekamelweni lalisengaphansi kwe-LTL ka-25 lapho kusetshenziswa amaqembu amathathu. Mhlawumbe umehluko obaluleke kakhulu we-Interpecies kulokhu mayelana nokubaluleka okuphezulu komsebenzi we-bat njengokuzivikela ku-hypothermia. Ngakho-ke, kanti amagundane anxephezelwa kakhulu ngokulahleka kwabo okuphezulu kwekhalori ngokukhuphula umsebenzi we-bat, okungaphezulu kwama-60% e-A ku-5 ° C. Ngakho-ke, ukunciphisa umsebenzi we-bat kungaba yindlela ebalulekile yokwandisa abantu bokuhumusha. Ukulawulwa komsebenzi we-bat kuyinkimbinkimbi kepha kuvame ukulungiswa yimiphumela ehlanganisiwe ye-adrenergic ukukhuthaza ukukhuthaza, ama-hormone e-thyroid kanye ne-UCP114,54,55,56,57,55,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,5,55,5,5,5,55 " Idatha yethu ikhombisa ukuthi izinga lokushisa lidinga ukunyuswa ngenhla kwe-27,5 ° C ngokuqhathaniswa namagundane ngo-22 ° C ukuze athole umehluko ekubonisweni kwezakhi zofuzo ze-bat ezibhekele ukusebenza / ukwenza kusebenze. Kodwa-ke, umehluko otholwe phakathi kwamaqembu ngo-30 no-22 ° C awukhombisa ngaso sonke isikhathi ukwanda komsebenzi we-bat ku-22 ° C group ngoba i-UCP1, i-ADRB2 ne-Vegff-A yaphenduka eqenjini lama-22 ° C Imbangela yale miphumela engalindelekile ihlala inqunywe. Kungenzeka ukuthi amazwi abo anda kakhulu angeke abonise isibonakaliso sokushisa segumbi eliphakeme, kodwa kunalokho okubangela ukuthi kube ngu-30 ° C kuya ku-22 ° C ngosuku imizuzu engu-5-10 ngaphambi kokuhamba) . ).
Ukulinganiselwa okujwayelekile kwesifundo sethu ukuthi sifunde amagundane abesilisa kuphela. Olunye ucwaningo lubonisa ukuthi ubulili bungaba ukucatshangelwa okubalulekile ezinhlelweni zethu eziyinhloko, njengoba amagundane abesifazane angashadile azwela kakhulu ngenxa yokuvuselelwa okuphezulu okushisayo nokugcina amazinga okushisa aphezulu alawulwa kakhulu. Ngaphezu kwalokho, amagundane abesifazane (ku-HFD) akhombise inhlangano enkulu yokuthathwa kwamandla nge-30 ° C uma iqhathaniswa namagundane abesilisa adla amagundane aphezulu wobulili obufanayo (20 ° C kulokhu) 20. Ngakho-ke, kumagundane abesifazane, okuqukethwe komhlaba angaphansi komhlaba kuphakeme, kepha kunendlela efanayo neyakwesilisa. Esifundweni sethu, sigxile kumagundane abesilisa abangokoqobo, ngoba lezi yizimo lapho iningi lezifundo ze-metabolic zihlola ngalo. Omunye umkhawulo wesifundo sethu ukuthi amagundane ayekudla okufanayo kulo lonke ucwaningo, okuvinjelwe ukutadisha ukubaluleka kokushisa kwekamelo lokuguquguquka kwe-metabolic (njengoba kulinganiswa ngezinguquko ze-RER zokwakheka kwe-macronutrient ezahlukahlukene). Egunjini labesifazane nabesilisa bagcinwe ngo-20 ° C uma kuqhathaniswa amagundane ahambisanayo agcinwe ngo-30 ° C.
Ekuphetheni, ukutadisha kwethu kukhombisa ukuthi, njengakwezinye izifundo, i-Lap 1 isisindo esijwayelekile yi-thermonethatral ngenhla okubikezelwe ngo-27,5 ° C. Ngaphezu kwalokho, ukutadisha kwethu kukhombisa ukuthi ukukhuluphala akusona isici esikhulu esibonisa ukufakwa emagukeni ngesisindo esijwayelekile noma i-DIO, okuholela ekushiseni okufanayo: I-EE Ratios in DIO kanye ne-Ejwayelekile Weight Mice. Ngenkathi ukudla okudlayo kwamagundane ajwayelekile bekuhambisana ne-ee ngakho-ke kwagcina isisindo somzimba esizinzile phezu kobubanzi bokushisa, ukuphuza ukudla kwe-dio mice bekufana namazinga okushisa ahlukene, okuholela ekulinganiselweni okuphezulu kwamagundane ngo-30 ° C . ngo-22 ° C uthole isisindo somzimba esiningi. Sekukonke, izifundo ezihlelekile ukuhlola ukubaluleka okungaba khona kokuphila ngaphansi kwamazinga okushisa we-thermonetharal kuvunyelwe ngenxa yokubekezelela okungabonakali okubonakalayo phakathi kwezifundo zegundane nezifundo zabantu. Isibonelo, ezifundweni zokukhuluphala, incazelo ethile yokuhumusha okumpofu kakhulu kungenzeka ngenxa yokuthi izifundo zokunciphisa umzimba isisindo zivame ukwenziwa ezilwaneni ezibandayo ezibandayo zigcinwe ngokushisa kwegumbi. Ukwehla kwesisindo okweqile okuqhathaniswa nesisindo somzimba esilindelekile somuntu, ikakhulukazi uma inqubo yesenzo incike ekwanda kwe-ee ngokwandisa umsebenzi we-BAP, osebenza kakhulu futhi asebenze ekushiseni kwegumbi kuneminyaka engama-30 ° C.
Ngokuya ngomthetho wokuhlola izilwane waseDenmark , 1985).
Amagundane we-C57BL asemasontweni angama-C57bl / 6J atholakala kuJanvier Saint Berthevin Cedex, eFrance, futhi anikezwe futhi anikezwe isikhangiso se-Libitum Clow (Altromin 1324) namanzi (~ 22 ° C) ngemuva kokukhanya kwehora le-12: 12 (° 22 ° C) Ngemuva kokukhanya kwehora le-12: 12. lokushisa kwegumbi. Amagundane ama-DIO wesilisa (amaviki angama-20) atholakala kumhlinzeki ofanayo futhi anikezwe ukufinyelela kwe-libitum okungu-45% Ukudla okuthe xaxa (ikati. No. D12451, ucwaningo lokudla kwe-Inc., NJ, USA) namanzi ngaphansi kwezimo zokukhulisa. Amagundane aguqulwa emvelweni ngesonto ngaphambi kokuqala kwesifundo. Ezinsukwini ezimbili ngaphambi kokudlulisela ohlelweni lwe-calorimettry olungaqondile, amagundane ayekalwa, afakwe ngaphansi kwe-MRI Scanning (eChomritm, TX, USA) futhi ahlukaniswe ngamaqembu amane ahambelana nesisindo somzimba, amafutha kanye nesisindo somzimba esijwayelekile.
Umdwebo we-graphic of the design ofundzelwayo ukhonjiswa kuMdwebo 8 amazinga emisebenzi ngokulinganisa ikhefu le-beam. I-XYZ. Amagundane (n = 8) agcinwe ngo-22, 25, 27.5, noma 30 ° C esebenzisa umbhede kodwa akukho ndawo yokukhosela kanye nesidleke esikhaleni esingu-12: Ukukhanya: Ukukhanya okumnyama: . 2500ml / min. Amagundane ahlehliswe izinsuku ezingama-7 ngaphambi kokubhalisa. Ukuqoshwa kwaqoqwa izinsuku ezine zilandelana. Ngemuva kwalokho, amagundane agcinwe emazingeni okushisa afanele ngo-25, 27,5, no-30 ° C ngezinsuku ezingezekile eziyi-12, ngemuva kwalokho okugxilwe kuseli kufakwe njengoba kuchazwe ngezansi. Ngaleso sikhathi, amaqembu amagundane agcinwe ngo-22 ° C agcinwe kulokhu kushisa izinsuku ezimbili (ukuqoqa idatha eyisisekelo emisha), bese izinga lokushisa lenyuke ngezinyathelo ze-2 ° C zonke ezinye izinsuku ( Ngo-06: 00) Kuze kube ukufinyelela ama-30 ° C emva kwalokho, izinga lokushisa lehliselwa ku-22 ° C kanye nedatha yaqoqwa ezinye izinsuku ezimbili. Ngemuva kwezinsuku ezimbili ezengeziwe zokuqoshwa ngo-22 ° C, izikhumba zengezwe kuwo wonke amaseli kuwo wonke amazinga okushisa, ukuqoqwa kwedatha kwaqala ngosuku lwesibili (usuku 17) nezinsuku ezintathu. Ngemuva kwaleso (usuku lwe-20), izidlo ezingezinhle (8-10 g) zengezwe kuwo wonke amaseli ekuqaleni komjikelezo wokukhanya (06:00) kanye nemininingwane yaqoqwa ezinye izinsuku ezintathu. Ngakho-ke, ekugcineni kocwaningo, amagundane agcinwe ngo-22 ° C. agcinwe kulokhu kushisa izinsuku ezingama-21/33 kwathi ngo-22 ° C ngezinsuku ezi-8 ezedlule, kanti amagundane kwamanye amazinga okushisa agcinwa kulokhu kushisa izinsuku ezingama-33. / Izinsuku ezingama-33. Amagundane andliwa ngesikhathi sokufunda.
Isisindo esijwayelekile ne-dio mice salandela izinqubo zokutadisha ezifanayo. Emini -9, amagundane asetshenziswa, i-MRI ihlolwe, futhi ihlukaniswe ngamaqembu aqhathaniswa nesisindo somzimba kanye nokwakhiwa komzimba. Ngosuku --7, amagundane adluliswa ekuvikelweni okuvaliwe okulawulwa yi-caloriment System okwenziwe ngeSinky Systems (Nevada, USA). Amagundane afakwa ngawodwana ngombhede kodwa ngaphandle kokudla noma izinto zokukhosela. Izinga lokushisa lisethelwe ku-22, 25, 27.5 noma 30 ° C. Ngemuva kweviki elilodwa le-Acclimatization (izinsuku -7 kuya ku-0, izilwane zazingaphazanyiswa), imininingwane yaqoqwa ngezinsuku ezine zilandelana (izinsuku 0-4, idatha ekhonjiswe kumakhiwane. 1, 2, 5). Ngemuva kwalokho, amagundane agcinwe ngo-25, 27.5 no-30 ° C bagcinwa ngaphansi kwezimo kuze kube usuku lwe-17. Ngasikhathi sinye, izinga lokushisa eqenjini le-22 ° C lakhuphuke ngezikhathi ezithile ze-2 ° C zonke ezinye izinsuku ngokulungisa umjikelezo wokushisa (06:00 h) ekuqaleni kokuvezwa kokukhanya (idatha ikhonjisiwe ku-Fig. 1) . Ngosuku 15, amazinga okushisa awela ku-22 ° C kanti kwaqoqwa izinsuku ezimbili zedatha ukuhlinzeka ngemininingwane eyisisekelo yokwelashwa okulandelayo. Izikhumba zanezelwa kubo bonke amagundane ngosuku lwe-17, kanti nezinto ezidliwe izidleke zangezwa ngosuku lwe-20 (Fig. 5). Ngosuku lwe-23, amagundane athathwa futhi athathwa nge-MRI Scanning, wabe esehamba ngedwa amahora angama-24. Ngosuku 24, amagundane adonswa ngokushesha kusukela ekuqaleni kwe-Photoperiod (06:00) futhi athola i-OGTT (2 g / kg) ngo-12: 00 (amahora angama-6-7 wokuzila). Ngemuva kwalokho, amagundane abuyiselwa ezimweni zawo ezihlanganayo futhi akhunjulwa ngosuku lwesibili (usuku 25).
I-Dio Mice (n = 8) ilandele iphrothokholi efanayo namagundane ajwayelekile wesisindo (njengoba kuchazwe ngenhla nakumfanekiso 8). Amagundane agcinwe ama-45% HFD kuwo wonke amathuba okusebenza kwemali.
I-VO2 ne-VCO2, kanye nengcindezi yamanzi ye-vapor, yaqoshwa imvamisa ye-1 hz nge-cell time cell engaphansi kwe-2,5 min. Ukudla nokudla kwamanzi kwaqoqwa ngokuqoshwa okuqhubekayo (1 hz) kwesisindo sokudla namapheyili wamanzi. Ukuqapha kwekhwalithi okusetshenzisiwe kubike isixazululo sika-0.002 g. Amazinga omsebenzi aqoshwa kusetshenziswa i-3D XYZ BEAM ArRAY Monitor, idatha yaqoqwa ekuxazululeni kwangaphakathi kwe-240 HZ futhi ibikwe umzuzwana ngamunye ukuze ihambe ibanga eliphelele elihambile (m) ngokulungiswa kwendawo okusebenzayo kwe-0.25 cm. Imininingwane icutshungulwe ngezinhlelo zeSals Macro Interpreter V.2.41, ukubala i-EE kanye nokuhlunga nokuhlunga okuphuma ngaphandle (isib. Izehlakalo zokudla zamanga). Umhumushi weMacro ulungiselelwe idatha yokukhipha kuwo wonke amapharamitha njalo ngemizuzu emihlanu.
Ngaphezu kokulawula i-EE, izinga lokushisa eli-Amient lingalawula futhi ezinye izici ze-metabolism, kufaka phakathi i-glucose metabolism yase-glucose-metaboling hormone. Ukuhlola le-hypothesis, ekugcineni saqeda isifundo sokushisa somzimba ngokuvusa amagundane ajwayelekile we-glucose (2 g / kg). Izindlela zichazwa ngokuningiliziwe kwezinto ezingeziwe.
Ekupheleni kwesifundo (usuku 25), amagundane asheshe asheshe (aqale ngo-06: 00), anesthetised nge-isoflurane, futhi aphathwe ngokuphelele yi-retroorbital venipuncture. Ukuqwashiswa kwama-lipids we-plasma nama-hormone nama-lipid esibindini kuchazwa ngezinto ezingezelelweyo.
Ukuphenya ukuthi ngabe izinga lokushisa le-Shell libangela yini izinguquko ze-hinsic ezifundweni ze-adipose ezithinta i-lipolysis, izicubu ze-ingunal ne-epididemal adipose zaxoshwa ngokuqondile kusuka kumagundane ngemuva kwesigaba sokugcina sokopha. Izicubu zazicutshungulwa kusetshenziswa i-ex vivolysis esanda kuthuthukiswa i-Assay echazwe ezindleleni ezengeziwe.
I-Brown Adipose Izicubu (i-bat) yaqoqwa ngosuku lokuphela kocwaningo futhi lucutshungulwe njengoba kuchazwe ngezindlela ezingezelelweyo.
Idatha yethulwa njenge-adve ± SEM. Graphs were created in GraphPad Prism 9 (La Jolla, CA) and graphics were edited in Adobe Illustrator (Adobe Systems Incorporated, San Jose, CA). Ukubaluleka kwezibalo kuhlolwe ku-graphpad prism futhi kuhlolwe nge-t-test paird, izinyathelo eziphindaphindwayo / i-anova ephindwe kabili elandelwa ukuhlolwa okuningiliswa kweTukey okuningi, noma i-ANOVA engavuthiwe elandelwa ukuhlolwa okuningiliswa kweTukey okuningi njengoba kudingeka. Ukusatshalaliswa kweGaussian kwemininingwane kuqinisekiswe yi-D'Agostino-Pearson Extarm Test ngaphambi kokuhlolwa. Usayizi wesampula ukhonjisiwe engxenyeni ehambisanayo yesigaba "semiphumela", kanye nakwinganekwane. Ukuphindaphinda kuchazwa njenganoma yisiphi isilinganiso esithathwe esilwaneni esifanayo (eVivo noma kwisampula yezicubu). Ngokuya ngembuyiselo yedatha, inhlangano phakathi kwezindleko zamandla kanye nokushisa kwamacala kwaboniswa ezifundweni ezine ezizimele isebenzisa amagundane ahlukahlukene anokwakhiwa okufanayo.
Imithetho enemininingwane yokuhlola, izinto zokwakha, kanye nedatha eluhlaza iyatholakala ngesicelo esivumelekile kusuka kuMlobi we-Lead All Rune E. Kuhre. Lolu cwaningo aluzange lukhiqize ama-reagents amasha ahlukile, izilwane ze-transgenic / cell imigqa, noma idatha yokulandelana.
Ngeminye imininingwane ekwakheni okufundwayo, bheka umbiko wokucwaninga wemvelo oxhumene nale ndatshana.
Yonke imininingwane yakha igrafu. I-1-7 ifakwe kwi-repository ye-database yesayensi, inombolo ye-action: 1253.11.Scientimentb.02284 noma https: //doi.org/10.5777/scianterb.02284. Imininingwane ekhonjiswe ku-ESM ingathunyelwa kuRune E Kuhle ngemuva kokuhlolwa okufanele.
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Isikhathi Sokuthumela: Oct-28-2022
