Ua tsaug rau koj tuaj xyuas Nature.com.Qhov browser version koj siv tau txwv CSS kev txhawb nqa.Rau qhov kev paub zoo tshaj plaws, peb xav kom koj siv qhov browser tshiab (lossis lov tes taw Compatibility Hom hauv Internet Explorer).Nyob rau lub sijhawm no, txhawm rau ua kom muaj kev txhawb nqa txuas ntxiv, peb yuav ua rau lub xaib tsis muaj qauv thiab JavaScript.
Feem ntau cov kev tshawb fawb metabolic hauv nas tau ua nyob rau hauv chav tsev kub, txawm hais tias nyob rau hauv cov xwm txheej no, tsis zoo li tib neeg, nas siv ntau lub zog tswj qhov kub thiab txias.Ntawm no, peb piav qhia txog qhov hnyav li qub thiab kev noj zaub mov vim kev rog rog (DIO) hauv C57BL / 6J nas noj chow chow lossis 45% kev noj zaub mov muaj roj ntau, feem.Cov nas tau muab tso rau 33 hnub ntawm 22, 25, 27.5 thiab 30 ° C. nyob rau hauv ib qho indirect calorimetry system.Peb qhia tau hais tias kev siv hluav taws xob nce linearly ntawm 30 ° C mus rau 22 ° C thiab yog li 30% siab dua ntawm 22 ° C hauv ob qho tib si nas qauv.Hauv cov nas qhov hnyav li qub, kev noj zaub mov tsis zoo tiv thaiv EE.Hloov pauv, DIO nas tsis txo cov khoom noj thaum EE txo.Yog li, thaum kawg ntawm txoj kev tshawb no, cov nas ntawm 30 ° C muaj lub cev hnyav dua, rog rog thiab ntshav glycerol thiab triglycerides tshaj cov nas ntawm 22 ° C.Qhov tsis sib xws hauv DIO nas tuaj yeem yog vim muaj kev lom zem ntau ntxiv.
Tus nas yog tus qauv siv tsiaj ntau tshaj plaws rau kev kawm txog tib neeg lub cev nqaij daim tawv thiab kab mob pathophysiology, thiab feem ntau yog cov tsiaj uas siv thaum ntxov ntawm kev tshawb pom thiab kev loj hlob ntawm cov tshuaj.Txawm li cas los xij, cov nas sib txawv ntawm tib neeg hauv ntau txoj hauv kev tseem ceeb ntawm lub cev, thiab thaum lub sij hawm allometric scaling yuav siv tau rau qee qhov kev txhais rau tib neeg, qhov sib txawv loj ntawm nas thiab tib neeg pw hauv thermoregulation thiab lub zog homeostasis.Qhov no qhia txog qhov tsis sib haum xeeb.Qhov nruab nrab lub cev hnyav ntawm cov nas laus yog tsawg kawg yog ib txhiab npaug tsawg dua li cov neeg laus (50 g vs. 50 kg), thiab thaj chaw saum npoo rau qhov sib piv loj sib txawv li ntawm 400 npaug vim qhov kev hloov pauv tsis-linear geometric piav qhia los ntawm Mee .Qhov sib npaug 2. Yog li ntawd, cov nas poob qis dua qhov kub ntawm lawv qhov ntim, yog li lawv muaj kev nkag siab zoo rau qhov kub thiab txias, ua rau hypothermia ntau dua, thiab muaj qhov nruab nrab basal metabolic tus nqi siab tshaj kaum npaug ntawm tib neeg.Ntawm chav tsev kub (~ 22 ° C), nas yuav tsum nce lawv cov nyiaj siv hluav taws xob tag nrho (EE) li ntawm 30% txhawm rau tswj lub cev kub.Ntawm qhov kub thiab txias, EE nce ntau dua li ntawm 50% thiab 100% ntawm 15 thiab 7 ° C piv rau EE ntawm 22 ° C.Yog li, cov txheej txheem vaj tsev nyob ua rau muaj kev ntxhov siab txias, uas tuaj yeem cuam tshuam kev hloov pauv ntawm cov txiaj ntsig nas rau tib neeg, vim tias tib neeg nyob hauv cov zej zog niaj hnub siv sijhawm feem ntau ntawm lawv lub sijhawm nyob rau hauv cov xwm txheej thermoneutral (vim tias peb cheeb tsam qis dua qhov chaw rau ntim ua rau peb tsis tshua nkag siab rau Qhov kub thiab txias, raws li peb tsim ib cheeb tsam thermoneutral (TNZ) nyob ib ncig ntawm peb EE saum toj no basal metabolic tus nqi) spans ~ 19 mus rau 30 ° C6, thaum nas muaj ib tug siab dua thiab nqaim band tsuas yog 2-4 ° C7,8 Qhov tseeb, qhov tseem ceeb no. nam tau txais kev saib xyuas zoo nyob rau xyoo tas los no 4, 7, 8, 9, 10, 11, 12 thiab nws tau pom tias qee qhov "hloov txawv" tuaj yeem txo tau los ntawm kev nce lub plhaub kub 9. Txawm li cas los xij, tsis muaj kev pom zoo ntawm qhov kub thiab txias. uas yog thermoneutrality hauv nas.Yog li, txawm tias qhov ntsuas kub tseem ceeb hauv qhov ntsuas kub hauv ib leeg-lub hauv caug nas yog ze rau 25 ° C lossis ze rau 30 ° C4, 7, 8, 10, 12 tseem muaj teeb meem.EE thiab lwm yam metabolic tsis tau txwv rau cov sij hawm rau ib hnub, yog li qhov ntev ntawm qhov sib txawv ntawm qhov kub thiab txias tuaj yeem cuam tshuam cov metabolic tsis xws li lub cev qhov hnyav.Kev noj haus, kev siv substrate, qabzib kam rau ua, thiab plasma lipid thiab qabzib concentration thiab qab los tswj cov tshuaj hormones.Tsis tas li ntawd, kev tshawb fawb ntxiv yog xav tau kom paub tseeb tias qhov kev noj haus twg yuav cuam tshuam rau cov kev txwv no (DIO nas ntawm kev noj zaub mov muaj roj ntau yuav ua rau muaj kev txaus siab rau kev noj zaub mov zoo (hedonic)).Txhawm rau muab cov ntaub ntawv ntau ntxiv ntawm cov ncauj lus no, peb tau tshuaj xyuas cov txiaj ntsig ntawm kev kho qhov kub thiab txias ntawm cov kab mob metabolic uas tau hais tseg hauv cov neeg laus cov txiv neej ib txwm hnyav thiab noj cov txiv neej rog rog (DIO) cov nas ntawm 45% cov zaub mov muaj roj ntau.Cov nas tau khaws cia ntawm 22, 25, 27.5, lossis 30 ° C rau tsawg kawg peb lub lis piam.Qhov kub qis dua 22 ° C tsis tau kawm vim tias cov tsiaj vaj tsev nyob tsis tshua muaj qis dua chav tsev.Peb pom tias cov nas ib txwm hnyav thiab ib lub voj voog DIO tau teb zoo ib yam li kev hloov pauv hauv qhov ntsuas kub ntawm EE thiab tsis hais txog ntawm qhov chaw kaw (nrog lossis tsis muaj chaw nyob / cov khoom siv zes).Txawm li cas los xij, thaum cov nas hnyav ib txwm hloov kho lawv cov zaub mov noj raws li EE, cov khoom noj ntawm DIO nas tau ywj siab ntawm EE, ua rau cov nas hnyav dua.Raws li cov ntaub ntawv ntawm lub cev hnyav, plasma concentrations ntawm lipids thiab ketone lub cev tau pom tias DIO nas ntawm 30 ° C muaj lub zog zoo dua li nas ntawm 22 ° C.Cov laj thawj hauv qab ntawm qhov sib txawv ntawm qhov sib npaug ntawm kev siv lub zog thiab EE ntawm qhov hnyav thiab DIO nas xav tau kev tshawb fawb ntxiv, tab sis tej zaum yuav cuam tshuam nrog kev hloov pauv pathophysiological hauv DIO nas thiab cov txiaj ntsig ntawm kev noj qab haus huv raws li kev noj zaub mov rog.
EE nce linearly ntawm 30 mus rau 22 ° C thiab yog li ntawm 30% siab dua ntawm 22 ° C piv rau 30 ° C (Fig. 1a, b).Qhov kev sib pauv ua pa (RER) tsis muaj qhov kub thiab txias (Daim duab 1c, d).Kev noj zaub mov zoo raws li EE dynamics thiab nce nrog txo qhov kub thiab txias (kuj ~ 30% siab dua ntawm 22 ° C piv rau 30 ° C (Fig. 1e,f). Dej tau txais. Qhov ntim thiab theem ua haujlwm tsis nyob ntawm qhov kub thiab txias (Fig. 1g).
Txiv neej nas (C57BL/6J, hnub nyoog 20 lub lis piam, ib tus neeg nyob hauv, n=7) tau nyob hauv cov kab mob metabolic ntawm 22 ° C. rau ib lub lis piam ua ntej pib kawm.Ob hnub tom qab sau cov ntaub ntawv keeb kwm yav dhau los, qhov kub tau nce hauv 2 ° C nce ntawm 06: 00 teev ib hnub (pib theem teeb).Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias ± tus qauv yuam kev ntawm qhov nruab nrab, thiab theem tsaus nti (18:00–06:00 h) yog sawv cev los ntawm lub thawv grey.a Kev siv hluav taws xob (kcal / h), b Tag nrho cov kev siv hluav taws xob ntawm qhov kub thiab txias (kcal / 24 h), c Kev sib hloov ua pa (VCO2 / VO2: 0.7–1.0), d Mean RER nyob rau hauv lub teeb thiab tsaus ntuj (VCO2 / VO2) theem (zero tus nqi txhais tau tias yog 0.7).e cumulative food intake (g), f 24h tag nrho cov zaub mov noj, g 24h tag nrho cov dej kom tsawg (ml), h 24h tag nrho cov dej kom tsawg, i cumulative yam dej num (m) thiab j tag nrho cov dej num (m/24h).).Cov nas tau khaws cia ntawm qhov ntsuas kub rau 48 teev.Cov ntaub ntawv qhia rau 24, 26, 28 thiab 30 ° C xa mus rau 24 teev dhau los ntawm txhua lub voj voog.Cov nas tseem noj thoob plaws qhov kev kawm.Kev ntsuas qhov tseem ceeb tau raug sim los ntawm kev ntsuas rov qab ntawm ib txoj kev ANOVA ua raws li Tukey qhov kev sib piv ntau yam.Asterisks qhia qhov tseem ceeb rau thawj tus nqi ntawm 22 ° C, shading qhia qhov tseem ceeb ntawm lwm pab pawg raws li qhia. *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.Tus nqi nruab nrab raug xam rau tag nrho lub sijhawm sim (0-192 teev).n = 7.
Raws li nyob rau hauv cov ntaub ntawv ntawm ib txwm hnyav nas, EE nce linearly nrog txo qhov kub thiab txias, thiab nyob rau hauv cov ntaub ntawv no, EE kuj yog hais txog 30% siab dua ntawm 22 ° C piv rau 30 ° C (Fig. 2a, b).RER tsis hloov ntawm qhov kub thiab txias (Daim duab 2c, d).Hauv qhov sib piv rau cov nas hnyav ib txwm, kev noj zaub mov tsis zoo nrog EE ua haujlwm ntawm chav tsev kub.Kev noj zaub mov, kev haus dej, thiab qib kev ua haujlwm tsis yog qhov kub thiab txias (Figs. 2e–j).
Txiv neej (C57BL/6J, 20 lub lis piam) DIO nas nyob ib leeg nyob rau hauv lub tawb metabolic ntawm 22 ° C. rau ib lub lis piam ua ntej pib txoj kev tshawb no.Cov nas tuaj yeem siv 45% HFD ad libitum.Tom qab acclimatization rau ob hnub, cov ntaub ntawv hauv paus tau sau.Tom qab ntawd, qhov kub thiab txias tau nce ntxiv ntawm 2 ° C txhua hnub ntawm 06:00 (pib theem teeb).Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias ± tus qauv yuam kev ntawm qhov nruab nrab, thiab theem tsaus nti (18:00–06:00 h) yog sawv cev los ntawm lub thawv grey.a Kev siv hluav taws xob (kcal / h), b Tag nrho cov kev siv hluav taws xob ntawm qhov kub thiab txias (kcal / 24 h), c Kev sib hloov ua pa (VCO2 / VO2: 0.7–1.0), d Mean RER nyob rau hauv lub teeb thiab tsaus ntuj (VCO2 / VO2) theem (zero tus nqi txhais tau tias yog 0.7).e cumulative food intake (g), f 24h tag nrho cov zaub mov noj, g 24h tag nrho cov dej kom tsawg (ml), h 24h tag nrho cov dej kom tsawg, i cumulative yam dej num (m) thiab j tag nrho cov dej num (m/24h).).Cov nas tau khaws cia ntawm qhov ntsuas kub rau 48 teev.Cov ntaub ntawv qhia rau 24, 26, 28 thiab 30 ° C xa mus rau 24 teev dhau los ntawm txhua lub voj voog.Cov nas tau khaws cia ntawm 45% HFD kom txog thaum kawg ntawm txoj kev tshawb no.Kev ntsuas qhov tseem ceeb tau raug sim los ntawm kev ntsuas rov qab ntawm ib txoj kev ANOVA ua raws li Tukey qhov kev sib piv ntau yam.Asterisks qhia qhov tseem ceeb rau thawj tus nqi ntawm 22 ° C, shading qhia qhov tseem ceeb ntawm lwm pab pawg raws li qhia. *P <0.05, ***P <0.001, ****P <0.0001. *P <0.05, ***P <0.001, ****P <0.0001. * 0,05, 0,001, **** 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. * 0,05, 0,001, **** 0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Tus nqi nruab nrab raug xam rau tag nrho lub sijhawm sim (0-192 teev).n = 7.
Hauv lwm qhov kev sim, peb tau tshuaj xyuas qhov cuam tshuam ntawm qhov kub thiab txias ntawm tib lub sijhawm, tab sis lub sijhawm no ntawm pawg nas uas tau khaws cia tas li ntawm qhov kub thiab txias.Cov nas tau muab faib ua plaub pawg kom txo qis kev hloov pauv hauv qhov nruab nrab thiab tus qauv sib txawv ntawm lub cev hnyav, rog, thiab lub cev hnyav (Fig. 3a–c).Tom qab 7 hnub ntawm acclimatization, 4.5 hnub ntawm EE raug kaw.EE muaj kev cuam tshuam loj heev los ntawm qhov kub thiab txias ob qho tib si thaum nruab hnub thiab hmo ntuj (Fig. 3d), thiab nce linearly raws li qhov kub thiab txias ntawm 27.5 ° C mus rau 22 ° C (Fig. 3e).Piv rau lwm pab pawg, RER ntawm 25 ° C pab pawg tau txo qis me ntsis, thiab tsis muaj qhov sib txawv ntawm cov pab pawg ntxiv (Fig. 3f,g).Kev noj zaub mov zoo ib yam li EE tus qauv nce li ntawm 30% ntawm 22 ° C piv rau 30 ° C (Fig. 3h, i).Kev siv dej thiab qib kev ua haujlwm tsis txawv ntawm pawg (Fig. 3j,k).Kev sib txawv ntawm qhov kub thiab txias mus txog 33 hnub tsis ua rau qhov sib txawv ntawm lub cev hnyav, lean loj, thiab rog rog ntawm cov pab pawg (Fig. 3n-s), tab sis ua rau txo qis hauv lub cev hnyav ntawm kwv yees li 15% piv rau Cov qhab nia qhia tus kheej (Daim duab 3n-s).3b, r, c.Hmoov tsis zoo, 30 ° C txee muaj qhov yuam kev calibration thiab tsis tuaj yeem muab cov ntaub ntawv EE thiab RER raug.
- Lub cev hnyav (a), lean loj (b) thiab rog rog (c) tom qab 8 hnub (ib hnub ua ntej hloov mus rau SABLE system).d Kev siv zog (kcal / h).e Kev siv hluav taws xob nruab nrab (0–108 teev) ntawm qhov kub thiab txias (kcal / 24 teev).f Respiratory exchange ratio (RER) (VCO2/VO2).g Mean RER (VCO2/VO2).h Tag nrho cov zaub mov noj (g).Kuv txhais tau tias noj mov (g/24 teev).j Tag nrho cov dej siv (ml).k Kev siv dej nruab nrab (ml / 24 h).l Qib kev ua ub no (m).m Qhov nruab nrab ntawm kev ua haujlwm (m / 24 teev).n lub cev hnyav rau hnub 18, o hloov lub cev hnyav (txij hnub -8 mus rau 18th), p lean loj rau hnub 18th, q hloov hauv lean mass (txij hnub -8 mus rau 18th), r rog rog hnub 18 , thiab hloov pauv hauv cov rog (los ntawm -8 mus rau 18 hnub).Cov txiaj ntsig tseem ceeb ntawm kev ntsuas rov qab tau sim los ntawm Oneway-ANOVA ua raws li Tukey qhov kev sib piv ntau yam. *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.Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias + tus qauv yuam kev ntawm qhov nruab nrab, lub sijhawm tsaus ntuj (18:00-06:00 h) yog sawv cev los ntawm cov thawv grey.Cov dots ntawm cov histograms sawv cev rau ib tus nas.Qhov nruab nrab cov nqi raug xam rau tag nrho lub sijhawm sim (0-108 teev).n = 7.
Cov nas tau sib npaug hauv lub cev qhov hnyav, qhov hnyav, thiab cov rog rog ntawm lub hauv paus (Daim duab 4a-c) thiab khaws cia ntawm 22, 25, 27.5, thiab 30 ° C raws li hauv kev tshawb fawb nrog cov nas qhov hnyav..Thaum muab piv rau cov nas, kev sib raug zoo ntawm EE thiab qhov kub thiab txias tau pom tias muaj kev sib raug zoo sib xws nrog qhov kub thiab txias dhau sijhawm hauv tib cov nas.Yog li, cov nas khaws cia ntawm 22 ° C siv li 30% ntau zog tshaj cov nas uas khaws cia ntawm 30 ° C (Fig. 4d, e).Thaum kawm txog cov teebmeem hauv cov tsiaj, qhov kub tsis tas yuav cuam tshuam rau RER (Fig. 4f,g).Kev noj zaub mov, kev noj dej, thiab kev ua si tsis cuam tshuam los ntawm qhov kub thiab txias (Figs. 4h–m).Tom qab 33 hnub ntawm kev yug me nyuam, cov nas ntawm 30 ° C muaj lub cev hnyav dua cov nas ntawm 22 ° C (Fig. 4n).Muab piv rau lawv cov ntsiab lus hauv qab no, cov nas uas nyob ntawm qhov kub ntawm 30 ° C muaj qhov hnyav dua lub cev hnyav dua cov nas uas nyob ntawm 22 ° C (txhais tau tias ± tus qauv yuam kev ntawm qhov txhais tau tias: Fig. 4o).Qhov hnyav hnyav dua yog vim qhov nce ntawm cov rog (Fig. 4p, q) es tsis yog qhov nce ntawm lean loj (Fig. 4r, s).Raws li qhov qis EE tus nqi ntawm 30 ° C, kev qhia ntawm ntau BAT noob uas nce BAT muaj nuj nqi / kev ua haujlwm tau txo qis ntawm 30 ° C piv rau 22 ° C: Adra1a, Adrb3, thiab Prdm16.Lwm cov noob tseem ceeb uas tseem nce BAT kev ua haujlwm / kev ua haujlwm tsis raug cuam tshuam: Sema3a (neurite txoj kev loj hlob), Tfam (mitochondrial biogenesis), Adrb1, Adra2a, Pck1 (gluconeogenesis) thiab Cpt1a.Kuj ceeb tias, Ucp1 thiab Vegf-a, cuam tshuam nrog kev ua haujlwm thermogenic, tsis txo qis hauv 30 ° C pab pawg.Qhov tseeb, Ucp1 qib hauv peb nas tau siab dua hauv pawg 22 ° C, thiab Vegf-a thiab Adrb2 tau nce siab.Piv nrog rau 22 ° C pab pawg, nas tswj ntawm 25 ° C thiab 27.5 ° C tsis pom qhov hloov pauv (Cov duab ntxiv 1).
- Lub cev hnyav (a), lean mass (b) thiab rog (c) tom qab 9 hnub (ib hnub ua ntej hloov mus rau SABLE system).d Zog noj (EE, kcal / h).e Kev siv hluav taws xob nruab nrab (0–96 teev) ntawm qhov kub thiab txias (kcal / 24 teev).f Kev sib pauv ua pa (RER, VCO2 / VO2).g Mean RER (VCO2/VO2).h Tag nrho cov zaub mov noj (g).Kuv txhais tau tias noj mov (g/24 teev).j Tag nrho cov dej siv (ml).k Kev siv dej nruab nrab (ml / 24 h).l Qib kev ua ub no (m).m Qhov nruab nrab ntawm kev ua haujlwm (m / 24 teev).n Lub cev hnyav ntawm hnub 23 (g), o Hloov hauv lub cev hnyav, p Lean loj, q Hloov hauv lean loj (g) ntawm hnub 23 piv rau hnub 9, Hloov cov rog (g) ntawm 23 -hnub, rog loj (g) piv rau hnub 8, hnub 23 piv rau -8th hnub.Cov txiaj ntsig tseem ceeb ntawm kev ntsuas rov qab tau sim los ntawm Oneway-ANOVA ua raws li Tukey qhov kev sib piv ntau yam. *P <0.05, ***P <0.001, ****P <0.0001. *P <0.05, ***P <0.001, ****P <0.0001. * 0,05, 0,001, **** 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. * 0,05, 0,001, **** 0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias + tus qauv yuam kev ntawm qhov nruab nrab, lub sijhawm tsaus ntuj (18:00-06:00 h) yog sawv cev los ntawm cov thawv grey.Cov dots ntawm cov histograms sawv cev rau ib tus nas.Qhov txiaj ntsig txhais tau raug xam rau tag nrho lub sijhawm sim (0-96 teev).n = 7.
Zoo li tib neeg, nas feem ntau tsim microenvironments kom txo tau cov cua sov rau ib puag ncig.Txhawm rau ntsuas qhov tseem ceeb ntawm ib puag ncig no rau EE, peb ntsuas EE ntawm 22, 25, 27.5, thiab 30 ° C, nrog lossis tsis muaj tawv tiv thaiv thiab cov khoom siv zes.Ntawm 22 ° C, qhov sib ntxiv ntawm cov tawv nqaij yuav txo tau EE li ntawm 4%.Tom qab ntxiv cov khoom siv zes txo cov EE los ntawm 3–4% (Fig. 5a,b).Tsis muaj kev hloov pauv tseem ceeb hauv RER, kev noj zaub mov, kev haus dej, lossis qib kev ua haujlwm tau pom nrog kev sib ntxiv ntawm tsev lossis tawv + txaj (Daim duab 5i–p).Qhov sib ntxiv ntawm daim tawv nqaij thiab cov khoom siv zes kuj txo qis EE ntawm 25 thiab 30 ° C, tab sis cov lus teb tau ntau dua.Ntawm 27.5 ° C tsis muaj qhov sib txawv.Qhov tseem ceeb, hauv cov kev sim no, EE txo qis nrog qhov kub thiab txias, hauv qhov no txog 57% qis dua EE ntawm 30 ° C piv rau 22 ° C (Fig. 5c-h).Tib qhov kev tshuaj ntsuam tau ua tsuas yog rau lub teeb theem, qhov twg EE tau ze dua rau qhov basal metabolic tus nqi, txij li qhov no cov nas feem ntau so hauv daim tawv nqaij, ua rau muaj qhov sib piv ntawm qhov sib piv ntawm qhov sib txawv ntawm qhov kub thiab txias (Supplementary Fig. 2a–h) .
Cov ntaub ntawv rau nas los ntawm chaw nyob thiab cov khoom zes (tsaus xiav), lub tsev tab sis tsis muaj cov khoom zes (lub teeb xiav), thiab cov khoom siv hauv tsev thiab zes (txiv kab ntxwv).Kev siv hluav taws xob (EE, kcal / h) rau chav a, c, e thiab g ntawm 22, 25, 27.5 thiab 30 ° C, b, d, f thiab h txhais tau tias EE (kcal / h).ip Cov ntaub ntawv rau cov nas nyob ntawm 22 ° C: kuv tus nqi ua pa (RER, VCO2 / VO2), j txhais tau tias RER (VCO2 / VO2), k cumulative food intake (g), l nruab nrab noj zaub mov (g / 24 h), m tag nrho cov dej tau txais (mL), n qhov nruab nrab dej tau txais AUC (mL / 24h), o tag nrho cov dej num (m), p nruab nrab ntawm cov dej num (m/24h).Cov ntaub ntawv tau nthuav tawm raws li qhov txhais tau tias + tus qauv yuam kev ntawm qhov nruab nrab, lub sijhawm tsaus ntuj (18:00-06:00 h) yog sawv cev los ntawm cov thawv grey.Cov dots ntawm cov histograms sawv cev rau ib tus nas.Cov txiaj ntsig tseem ceeb ntawm kev ntsuas rov qab tau sim los ntawm Oneway-ANOVA ua raws li Tukey qhov kev sib piv ntau yam. *P <0.05, **P <0.01. *P <0.05, **P <0.01. *A<0,05,**0,01. *P<0.05, **P<0.01. *P <0.05,**P <0.01. *P <0.05,**P <0.01. *A<0,05,**0,01. *P<0.05, **P<0.01.Tus nqi nruab nrab raug xam rau tag nrho lub sijhawm sim (0-72 teev).n = 7.
Hauv cov nas yuag ib txwm (2-3 teev ntawm kev yoo mov), kev txhawb nqa ntawm qhov sib txawv ntawm qhov kub tsis tau ua rau muaj qhov sib txawv ntawm cov ntshav plasma ntau ntawm TG, 3-HB, cov roj cholesterol, ALT, thiab AST, tab sis HDL ua haujlwm kub.Daim duab 6a-e).Kev yoo mov plasma concentration ntawm leptin, insulin, C-peptide, thiab glucagon kuj tsis txawv ntawm pawg (Figures 6g-j).Nyob rau hnub ntawm kev kuaj ntshav qabzib (tom qab 31 hnub ntawm qhov kub sib txawv), cov ntshav qabzib theem pib (5-6 teev yoo mov) yog kwv yees li 6.5 mM, tsis muaj qhov sib txawv ntawm cov pab pawg. Kev tswj hwm cov piam thaj hauv qhov ncauj nce ntshav qabzib ntau hauv txhua pab pawg, tab sis ob qho tib si ncov siab thiab qhov chaw nce ntxiv hauv qab nkhaus (iAUCs) (15-120 min) qis dua hauv pab pawg nas nyob ntawm 30 ° C (cov ntsiab lus ntawm tus kheej lub sijhawm: P <0.05–P <0.0001, Fig. 6k, l) piv rau cov nas nyob ntawm 22, 25 thiab 27.5 ° C (uas tsis txawv ntawm ib leeg). Kev tswj hwm cov piam thaj hauv qhov ncauj nce ntshav qabzib ntau hauv txhua pab pawg, tab sis ob qho tib si ncov siab thiab qhov chaw nce ntxiv hauv qab nkhaus (iAUCs) (15-120 min) qis dua hauv pab pawg nas nyob ntawm 30 ° C (cov ntsiab lus ntawm tus kheej lub sijhawm: P <0.05–P < 0.0001, Fig. 6k, l) piv rau cov nas nyob ntawm 22, 25 thiab 27.5 ° C (uas tsis txawv ntawm ib leeg). Пероральное гльние глроначитение гоначительно Овацию кро вови викак кковая контоя, Txawm li cas los xij (соли мивыми (ITUC) (15-120 Миж жжжжжжж 30 30 ° C ( : P < 0,05–P < 0,0001, рис. 6k, l) по сравнению с мышами, содержащимися при 22, 25 и 27,5 ° C (котоблые нерадей). Kev tswj hwm qhov ncauj ntawm cov piam thaj ua rau cov ntshav qabzib ntau ntxiv hauv txhua pab pawg, tab sis ob qho tib si ncov siab thiab qhov chaw nce ntxiv hauv qab nkhaus (iAUC) (15-120 min) qis dua hauv 30 ° C nas pawg (cov ntsiab lus sib cais: P < 0.05- P <0.0001, Fig. 6k, l) piv rau cov nas khaws cia ntawm 22, 25 thiab 27.5 ° C (uas tsis txawv ntawm ib leeg).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 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。口服葡萄糖的给药 显着了 所有组的 血糖 浓度但在在 30°C 饲养 小鼠绦岓中，增加 面积 面积 (IAUC) (15-120 分钟) 均 较低各 个点点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。Kev tswj hwm qhov ncauj ntawm cov piam thaj ua rau cov ntshav qabzib ntau ntxiv hauv txhua pab pawg, tab sis ob qho tib si ncov siab thiab thaj chaw hauv qab nkhaus (iAUC) (15-120 min) qis dua hauv 30 ° C-fed nas pawg (txhua lub sijhawm cov ntsiab lus).: P < 0,05–P < 0,0001, рис. : P < 0.05–P < 0.0001, Fig.6l, l) piv nrog cov nas khaws cia ntawm 22, 25 thiab 27.5 ° C (tsis txawv ntawm ib leeg).
Plasma concentrations ntawm TG, 3-HB, roj cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, thiab glucagon yog pom nyob rau hauv cov txiv neej laus DIO (al) nas tom qab 33 hnub ntawm kev pub noj ntawm qhov ntsuas kub. .Cov nas tsis tau noj 2-3 teev ua ntej kuaj ntshav.Qhov tshwj xeeb yog kev ntsuas qhov ncauj qhov ncauj, uas tau ua ob hnub ua ntej qhov kawg ntawm txoj kev tshawb no ntawm cov nas yoo mov rau 5-6 teev thiab khaws cia ntawm qhov kub thiab txias rau 31 hnub.Cov nas tau sib tw nrog 2 g / kg lub cev hnyav.Lub cheeb tsam nyob rau hauv cov ntaub ntawv nkhaus (L) yog qhia raws li incremental data (iAUC).Cov ntaub ntawv raug nthuav tawm raws li txhais tau tias ± SEM.Cov dots sawv cev rau tus kheej cov qauv. *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.
Hauv DIO nas (tseem yoo mov rau 2-3 teev), plasma cholesterol, HDL, ALT, AST, thiab FFA concentrations tsis txawv ntawm pawg.Ob leeg TG thiab glycerol tau nce siab hauv pawg 30 ° C piv rau 22 ° C pawg (Figures 7a-h).Hauv qhov sib piv, 3-GB yog kwv yees li 25% qis dua ntawm 30 ° C piv rau 22 ° C (Daim duab 7b).Yog li, txawm hais tias cov nas tuav ntawm 22 ° C muaj tag nrho lub zog zoo sib npaug, raws li tau hais los ntawm qhov hnyav nce, qhov sib txawv ntawm cov ntshav plasma ntau ntawm TG, glycerol, thiab 3-HB qhia tias cov nas ntawm 22 ° C thaum cov qauv qis dua ntawm 22 °. C.°C.Cov nas uas nyob ntawm 30 ° C tau nyob rau hauv lub xeev uas muaj zog ntau dua.Raws li qhov no, daim siab concentrations ntawm extractable glycerol thiab TG, tab sis tsis glycogen thiab cholesterol, yog siab dua nyob rau hauv 30 ° C pab pawg neeg (Ntxiv daim duab 3a-d).Txhawm rau tshawb xyuas seb qhov kub ntawm qhov sib txawv ntawm lipolysis (raws li ntsuas los ntawm plasma TG thiab glycerol) yog qhov tshwm sim ntawm kev hloov pauv sab hauv hauv epididymal lossis inguinal rog, peb tau rho tawm cov ntaub so ntswg adipose los ntawm cov khw muag khoom thaum kawg ntawm txoj kev tshawb no thiab suav cov roj fatty acids. vivo.thiab tso tawm glycerol.Hauv txhua pawg kev sim, cov qauv adipose cov ntaub so ntswg los ntawm epididymal thiab inguinal depots tau pom tsawg kawg ob zaug nce ntawm glycerol thiab FFA ntau lawm nyob rau hauv teb rau isoproterenol stimulation (Supplementary Fig. 4a–d).Txawm li cas los xij, tsis muaj qhov cuam tshuam ntawm lub plhaub kub ntawm basal lossis isoproterenol-stimulated lipolysis tau pom.Raws li qhov hnyav ntawm lub cev hnyav thiab rog rog, qib plasma leptin tau nce siab hauv pawg 30 ° C dua li ntawm 22 ° C pawg (Daim duab 7i).Ntawm qhov tsis sib xws, plasma qib ntawm insulin thiab C-peptide tsis txawv ntawm cov pab pawg kub (Daim duab 7k, k), tab sis plasma glucagon qhia qhov kev cia siab ntawm qhov kub thiab txias, tab sis qhov no yuav luag 22 ° C hauv pawg neeg sib txawv yog ob zaug piv. rau 30 ° C.Los ntawm.Pawg C (Fig. 7l).FGF21 tsis txawv ntawm cov pab pawg kub sib txawv (Fig. 7m).Hnub ntawm OGTT, cov ntshav qabzib hauv qab yog kwv yees li 10 mM thiab tsis txawv ntawm cov nas nyob ntawm qhov kub sib txawv (Fig. 7n).Kev tswj hwm qhov ncauj ntawm cov piam thaj hauv cov ntshav nce siab thiab nce siab hauv txhua pab pawg ntawm qhov siab ntawm 18 mM 15 feeb tom qab noj.Tsis muaj qhov sib txawv tseem ceeb hauv iAUC (15–120 min) thiab qhov sib txawv ntawm lub sijhawm sib txawv ntawm cov ntsiab lus tom qab koob tshuaj (15, 30, 60, 90 thiab 120 min) (Daim duab 7n, o).
Plasma concentrations ntawm TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, glucagon, thiab FGF21 tau pom nyob rau hauv cov txiv neej laus DIO (ao) nas tom qab 33 hnub pub mis.ntsuas kub.Cov nas tsis tau noj 2-3 teev ua ntej kuaj ntshav.Qhov kev kuaj ntshav qabzib hauv qhov ncauj yog qhov tshwj xeeb vim nws tau ua ntawm koob tshuaj 2 g / kg lub cev hnyav ob hnub ua ntej qhov kawg ntawm kev tshawb fawb hauv cov nas uas tau yoo mov rau 5-6 teev thiab khaws cia ntawm qhov kub thiab txias rau 31 hnub.Lub cheeb tsam nyob rau hauv cov ntaub ntawv nkhaus (o) yog qhia raws li incremental data (iAUC).Cov ntaub ntawv raug nthuav tawm raws li txhais tau tias ± SEM.Cov dots sawv cev rau tus kheej cov qauv. *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.
Kev hloov pauv ntawm cov ntaub ntawv nas rau tib neeg yog qhov teeb meem nyuaj uas ua lub luag haujlwm tseem ceeb hauv kev txhais cov ntsiab lus tseem ceeb ntawm kev soj ntsuam hauv cov ntsiab lus ntawm kev tshawb fawb physiological thiab pharmacological.Rau cov laj thawj kev lag luam thiab txhawm rau pab txhawb kev tshawb fawb, nas feem ntau khaws cia hauv chav sov hauv qab lawv thaj chaw thermoneutral, ua rau muaj kev ua kom muaj ntau yam kev siv lub cev ua kom lub cev ua kom cov metabolism thiab ua rau muaj kev cuam tshuam kev txhais lus9.Yog li, kev raug cov nas txias tuaj yeem ua rau cov nas tiv thaiv kev noj zaub mov vim kev rog rog thiab tuaj yeem tiv thaiv hyperglycemia hauv streptozotocin-kho nas vim muaj kev thauj mus los tsis yog-insulin-dependent glucose.Txawm li cas los xij, nws tsis paub meej txog qhov ntev npaum li cas raug rau ntau qhov ntsuas kub (los ntawm chav tsev mus rau thermoneutral) cuam tshuam rau lub zog sib txawv homeostasis ntawm cov nas yuag ib txwm (ntawm cov khoom noj) thiab DIO nas (ntawm HFD) thiab cov kab mob metabolic, nrog rau ntau npaum li cas. uas lawv muaj peev xwm sib npaug ntawm qhov nce hauv EE nrog kev nce hauv kev noj zaub mov.Txoj kev tshawb no nthuav tawm hauv kab lus no txhawm rau coj qee qhov pom tseeb rau lub ncauj lus no.
Peb qhia tau hais tias nyob rau hauv ib txwm hnyav cov neeg laus nas thiab txiv neej DIO nas, EE yog inversely cuam tshuam rau chav tsev kub ntawm 22 thiab 30 ° C.Yog li, EE ntawm 22 ° C yog li 30% siab dua ntawm 30 ° C.nyob rau hauv ob qho tib si nas qauv.Txawm li cas los xij, qhov sib txawv tseem ceeb ntawm cov nas yuag ib txwm thiab DIO nas yog tias thaum cov nas yuag ib txwm sib npaug EE ntawm qhov kub thiab txias los ntawm kev kho cov khoom noj kom haum, kev noj zaub mov ntawm DIO nas sib txawv ntawm ntau qib.Qhov ntsuas kub tau zoo sib xws.Tom qab ib hlis, DIO nas khaws cia ntawm 30 ° C tau nce lub cev hnyav thiab rog ntau dua cov nas khaws cia ntawm 22 ° C, thaum tib neeg ib txwm khaws cia ntawm qhov kub thiab txias rau tib lub sijhawm tsis ua rau kub taub hau.nyob ntawm qhov sib txawv ntawm lub cev hnyav.yuag nas.Piv nrog rau qhov kub thiab txias nyob ze thermoneutral los yog nyob rau hauv chav tsev kub, kev loj hlob ntawm chav tsev kub ua rau DIO los yog ib txwm yuag nas nyob rau hauv cov zaub mov muaj roj, tab sis tsis nyob rau hauv ib tug ib txwm yuag nas noj cov zaub mov kom nce kuj yuag.lub cev.Txhawb nqa los ntawm lwm cov kev tshawb fawb17,18,19,20,21 tab sis tsis yog los ntawm tag nrho 22,23.
Lub peev xwm los tsim ib puag ncig microenvironment kom txo tau cov cua sov yog hypothesized hloov thermal neutrality mus rau sab laug8, 12. Hauv peb txoj kev tshawb fawb, ob qho tib si ntxiv cov khoom siv zes thiab zais txo qis EE tab sis tsis ua rau thermal neutrality mus txog 28 ° C.Yog li, peb cov ntaub ntawv tsis txhawb nqa qhov qis ntawm thermoneutrality nyob rau hauv ib leeg-lub hauv caug cov neeg laus nas, nrog los yog tsis muaj ib puag ncig enriched tsev, yuav tsum yog 26-28 ° C raws li qhia 8,12, tab sis nws txhawb lwm yam kev tshawb fawb qhia thermoneutrality.Qhov kub thiab txias ntawm 30 ° C hauv cov nas qis 7, 10, 24. Yuav ua rau muaj teeb meem nyuaj, qhov ntsuas thermoneutral hauv nas tau pom tias tsis zoo li qub thaum nruab hnub vim tias nws qis dua thaum lub sij hawm so (lub teeb), tej zaum yog vim qis calories. kev tsim tawm los ntawm kev ua haujlwm thiab kev noj zaub mov-induced thermogenesis.Yog li, nyob rau hauv lub teeb theem, qhov qis ntawm thermal nruab nrab hloov mus rau ~ 29 ° C, thiab nyob rau hauv maub theem, ~ 33 ° C 25.
Thaum kawg, kev sib raug zoo ntawm ambient kub thiab tag nrho lub zog noj yog txiav txim los ntawm tshav kub dissipation.Hauv cov ntsiab lus no, qhov sib piv ntawm thaj chaw ntawm thaj chaw rau qhov ntim yog qhov tseem ceeb ntawm kev txiav txim siab ntawm thermal rhiab heev, cuam tshuam rau ob qho tib si tshav kub dissipation (surface area) thiab tshav kub tsim (ntim).Ntxiv rau qhov chaw saum npoo av, kev hloov hluav taws xob kuj tau txiav txim siab los ntawm kev rwb thaiv tsev (tus nqi ntawm cov cua sov hloov).Hauv tib neeg, cov rog rog tuaj yeem txo cov cua sov los ntawm kev tsim kom muaj qhov thaiv thaiv ib puag ncig ntawm lub cev lub plhaub, thiab nws tau pom tias cov rog rog kuj tseem ceeb rau kev rwb thaiv tsev thermal hauv nas, txo qis qhov ntsuas kub thiab txo qhov kub thiab txias hauv qab lub thermal nruab nrab point ( txoj kab nqes).ambient kub piv rau EE) 12.Peb txoj kev tshawb fawb tsis tau tsim los soj ntsuam ncaj qha rau qhov kev sib raug zoo no vim hais tias lub cev muaj pes tsawg leeg cov ntaub ntawv tau sau 9 hnub ua ntej cov ntaub ntawv siv hluav taws xob tau sau thiab vim tias cov rog rog tsis ruaj khov thoob plaws hauv txoj kev tshawb no.Txawm li cas los xij, txij li qhov hnyav li qub thiab DIO nas muaj 30% qis EE ntawm 30 ° C dua li ntawm 22 ° C txawm tias tsawg kawg yog 5-fold sib txawv ntawm cov rog rog, peb cov ntaub ntawv tsis txhawb tias kev rog rog yuav tsum muab cov rwb thaiv tsev yooj yim.qhov tseem ceeb, yam tsawg kawg tsis nyob rau hauv qhov ntsuas kub ntsuas.Qhov no yog nyob rau hauv txoj kab nrog rau lwm cov kev tshawb fawb zoo tsim los tshawb txog qhov no 4,24.Nyob rau hauv cov kev tshawb fawb no, cov nyhuv insulating ntawm kev rog yog me me, tab sis plaub pom tau muab 30-50% ntawm tag nrho cov thermal rwb thaiv tsev4,24.Txawm li cas los xij, hauv cov nas tuag, thermal conductivity nce li 450% tam sim ntawd tom qab tuag, qhia tias cov nyhuv insulating ntawm cov plaub yog tsim nyog rau cov txheej txheem ntawm lub cev, suav nrog vasoconstriction, ua haujlwm.Ntxiv rau qhov sib txawv ntawm cov tsiaj ntawm cov nas thiab tib neeg, cov nyhuv tsis zoo ntawm kev rog rog hauv cov nas kuj tuaj yeem cuam tshuam los ntawm cov kev xav hauv qab no: Lub insulating yam ntawm tib neeg cov rog rog feem ntau yog kho los ntawm subcutaneous rog (thickness) 26,27.Feem ntau hauv cov nas tsawg dua 20% ntawm tag nrho cov tsiaj rog28.Tsis tas li ntawd, tag nrho cov rog rog yuav tsis yog qhov kev ntsuas zoo tshaj plaws ntawm ib tus neeg lub thermal rwb thaiv tsev, raws li nws tau sib cav hais tias kev txhim kho thermal rwb thaiv tsev yog offset los ntawm qhov tsis tuaj yeem nce hauv cheeb tsam saum npoo (thiab yog li ua kom kub poob) raws li cov rog loj..
Hauv cov nas yuag ib txwm, ceev cov ntshav ntshav ntau ntawm TG, 3-HB, cov roj cholesterol, HDL, ALT, thiab AST tsis hloov pauv ntawm qhov kub thiab txias rau yuav luag 5 lub lis piam, tej zaum vim tias cov nas nyob hauv tib lub zog sib npaug.tau tib yam hauv qhov hnyav thiab lub cev muaj pes tsawg leeg raws li qhov kawg ntawm txoj kev tshawb no.Raws li qhov zoo sib xws hauv cov rog rog, kuj tseem tsis muaj qhov sib txawv ntawm cov qib plasma leptin, lossis hauv kev yoo mov insulin, C-peptide, thiab glucagon.Ntau cov cim tau pom hauv DIO nas.Txawm hais tias cov nas ntawm 22 ° C kuj tsis muaj qhov tsis zoo tag nrho hauv lub xeev no (raws li lawv tau nce qhov hnyav), thaum kawg ntawm txoj kev tshawb fawb lawv tau muaj zog ntau dua piv rau cov nas uas nyob ntawm 30 ° C, hauv cov xwm txheej xws li siab ketones.kev tsim tawm los ntawm lub cev (3-GB) thiab txo qis ntawm glycerol thiab TG hauv ntshav.Txawm li cas los xij, qhov sib txawv ntawm qhov kub thiab txias hauv lipolysis tsis tshwm sim los ntawm qhov kev hloov pauv hauv cov kab mob epididymal lossis inguinal rog, xws li kev hloov pauv hauv kev qhia ntawm adipohormone-responsive lipase, txij li FFA thiab glycerol tso tawm los ntawm cov roj muab rho tawm los ntawm cov depots no nyob nruab nrab ntawm qhov kub thiab txias. pab pawg zoo ib yam.Txawm hais tias peb tsis tau tshawb xyuas cov suab paj nruag hauv txoj kev tshawb fawb tam sim no, lwm tus tau pom tias nws (raws li lub plawv dhia thiab txhais tau tias cov hlab ntsha siab) yog linearly cuam tshuam rau ambient kub hauv nas thiab yog kwv yees li qis dua ntawm 30 ° C dua li ntawm 22 ° C 20%. C Yog li, qhov sib txawv ntawm qhov kub thiab txias hauv cov suab paj nruag tuaj yeem ua lub luag haujlwm hauv lipolysis hauv peb txoj kev tshawb fawb, tab sis txij li qhov nce hauv kev sib haum xeeb tone txhawb ntau dua li inhibits lipolysis, lwm cov txheej txheem tuaj yeem tiv thaiv qhov txo qis hauv cov nas.Lub luag haujlwm muaj peev xwm hauv kev rhuav tshem lub cev rog.Chav kub.Tsis tas li ntawd, ib feem ntawm cov nyhuv stimulatory ntawm sympathetic tone ntawm lipolysis yog indirect mediated los ntawm muaj zog inhibition ntawm insulin secretion, qhia txog cov nyhuv ntawm insulin cuam tshuam supplementation ntawm lipolysis 30, tab sis nyob rau hauv peb txoj kev tshawb no, yoo mov plasma insulin thiab C-peptide sympathetic tone ntawm txawv qhov kub thiab txias. tsis txaus los hloov lipolysis.Hloov chaw, peb pom tias qhov sib txawv ntawm lub zog muaj zog feem ntau yog qhov tseem ceeb rau qhov sib txawv ntawm DIO nas.Cov laj thawj hauv qab uas ua rau muaj kev tswj hwm zoo dua ntawm kev noj zaub mov nrog EE hauv cov nas qhov hnyav ib txwm xav tau kev kawm ntxiv.Feem ntau, txawm li cas los xij, kev noj zaub mov yog tswj los ntawm homeostatic thiab hedonic cues31,32,33.Txawm hais tias muaj kev sib cav txog qhov twg ntawm ob lub cim tseem ceeb dua, 31, 32, 33 nws tau paub zoo tias kev noj zaub mov muaj roj mus ntev ua rau muaj kev lom zem ntau dua li kev noj qab haus huv uas yog qee yam tsis cuam tshuam nrog. homeostasis..- tswj kev noj zaub mov 34,35,36.Yog li, kev noj zaub mov ntau ntxiv ntawm DIO nas kho nrog 45% HFD yuav yog ib qho laj thawj vim li cas cov nas no tsis sib npaug ntawm kev noj zaub mov nrog EE.Interestingly, qhov sib txawv ntawm qab los noj mov thiab cov ntshav qabzib tswj cov tshuaj hormones kuj tau pom nyob rau hauv cov nas ntsuas kub DIO, tab sis tsis nyob rau hauv cov nas qhov hnyav.Hauv DIO nas, plasma leptin qib nce nrog qhov kub thiab txias thiab glucagon qib txo nrog qhov kub thiab txias.Qhov twg qhov kub thiab txias tuaj yeem cuam tshuam ncaj qha rau cov kev sib txawv no tsim nyog kawm ntxiv, tab sis nyob rau hauv cov ntaub ntawv ntawm leptin, cov txheeb ze tsis zoo zog tshuav nyiaj li cas thiab yog li txo cov rog rog hauv cov nas ntawm 22 ° C yeej ua lub luag haujlwm tseem ceeb, raws li cov rog rog thiab ntshav leptin yog. kev sib raug zoo heev 37.Txawm li cas los xij, kev txhais ntawm glucagon teeb liab yog qhov nyuaj dua.Raws li cov tshuaj insulin, glucagon secretion tau cuam tshuam los ntawm kev nce siab hauv lub siab, tab sis qhov siab tshaj plaws ntawm lub siab tau kwv yees tias yog nyob rau hauv 22 ° C pab pawg, uas muaj qhov siab tshaj plaws ntawm plasma glucagon concentrations.Insulin yog lwm lub zog tswj hwm ntawm plasma glucagon, thiab insulin tsis kam thiab hom 2 mob ntshav qab zib muaj feem cuam tshuam nrog kev yoo mov thiab postprandial hyperglucagonemia 38,39.Txawm li cas los xij, DIO nas hauv peb txoj kev tshawb fawb kuj tseem muaj cov tshuaj insulin tsis txaus, yog li qhov no kuj tsis tuaj yeem yog qhov tseem ceeb hauv kev nce glucagon signaling hauv 22 ° C pawg.Lub siab rog cov ntsiab lus kuj tseem cuam tshuam nrog kev nce hauv cov ntshav plasma glucagon concentration, cov txheej txheem ntawm cov txheej txheem uas, nyob rau hauv lem, yuav muaj xws li hepatic glucagon tsis kam, txo urea ntau lawm, nce circulating amino acid concentrations, thiab nce amino acid-stimulated glucagon secretion40,41, 42.Txawm li cas los xij, txij li cov txiaj ntsig tau txais txiaj ntsig ntawm glycerol thiab TG tsis txawv ntawm cov pab pawg kub hauv peb txoj kev tshawb fawb, qhov no kuj tsis tuaj yeem yog qhov tseem ceeb hauv kev nce ntshav plasma concentration hauv 22 ° C pawg.Triiodothyronine (T3) plays lub luag haujlwm tseem ceeb hauv tag nrho cov metabolic tus nqi thiab pib ntawm metabolic tiv thaiv tiv thaiv hypothermia43,44.Yog li, plasma T3 concentration, tejzaum nws tswj los ntawm centrally mediated mechanisms, 45,46 nce nyob rau hauv cov nas thiab tib neeg nyob rau hauv tsawg tshaj li thermoneutral tej yam kev mob 47, txawm hais tias qhov nce nyob rau hauv tib neeg yog me me, uas yog predisposed rau nas.Qhov no yog ua raws li kev poob cua sov rau ib puag ncig.Peb tsis tau ntsuas plasma T3 concentrations hauv txoj kev tshawb fawb tam sim no, tab sis cov concentration yuav qis dua hauv 30 ° C pab pawg, uas tuaj yeem piav qhia cov txiaj ntsig ntawm pab pawg no ntawm qib plasma glucagon, raws li peb (hloov daim duab 5a) thiab lwm tus tau qhia tias. T3 nce plasma glucagon nyob rau hauv ib qho kev noj tshuaj.Cov thyroid hormones tau tshaj tawm tias yuav ua rau FGF21 qhia hauv daim siab.Zoo li glucagon, plasma FGF21 concentrations kuj nce nrog plasma T3 concentrations (Ntxiv Fig. 5b thiab ref. 48), tab sis piv rau glucagon, FGF21 plasma concentrations hauv peb txoj kev tshawb fawb tsis cuam tshuam los ntawm qhov kub thiab txias.Cov laj thawj hauv qab ntawm qhov tsis sib xws no yuav tsum tau kawm ntxiv, tab sis T3-tsav FGF21 induction yuav tsum tshwm sim nyob rau theem siab dua ntawm T3 raug piv rau qhov pom T3-tsav glucagon teb (Ntxiv Fig. 5b).
HFD tau pom tias muaj kev cuam tshuam nrog kev ua haujlwm tsis zoo ntawm cov piam thaj thiab insulin tsis kam (cov cim) hauv cov nas uas nyob ntawm 22 ° C.Txawm li cas los xij, HFD tsis cuam tshuam nrog cov piam thaj tsis txaus siab lossis insulin tsis kam thaum loj hlob hauv ib puag ncig thermoneutral (txhais tau ntawm no yog 28 ° C) 19 .Hauv peb txoj kev tshawb fawb, qhov kev sib raug zoo no tsis tau rov ua dua hauv DIO nas, tab sis cov nas hnyav ib txwm khaws cia ntawm 30 ° C ua rau muaj txiaj ntsig zoo dua cov piam thaj.Yog vim li cas rau qhov sib txawv no yuav tsum tau kawm ntxiv, tab sis tej zaum yuav cuam tshuam los ntawm qhov tseeb tias DIO nas nyob rau hauv peb txoj kev tshawb fawb yog insulin resistant, nrog ceev ceev plasma C-peptide concentrations thiab insulin concentrations 12-20 npaug ntau dua li cov nas yuag.thiab nyob rau hauv cov ntshav ntawm lub plab khoob.Cov piam thaj ntau li 10 mM (kwv yees li 6 mM ntawm lub cev hnyav), uas zoo li tawm hauv lub qhov rais me me rau txhua qhov muaj txiaj ntsig zoo ntawm kev cuam tshuam rau thermoneutral tej yam kev mob los txhim kho cov piam thaj ntev.Ib qho ua tau tsis meej pem yog tias, rau qhov ua tau zoo, OGTT yog nqa tawm ntawm chav tsev kub.Yog li, cov nas nyob ntawm qhov kub siab dua tau ntsib qhov mob khaub thuas me me, uas tuaj yeem cuam tshuam rau kev nqus cov piam thaj / tshem tawm.Txawm li cas los xij, raws li cov ntshav qabzib yoo mov zoo sib xws hauv cov pab pawg kub sib txawv, kev hloov pauv ntawm qhov kub thiab txias yuav tsis cuam tshuam rau cov txiaj ntsig.
Raws li tau hais ua ntej, nws tsis ntev los no tau hais tias qhov nce hauv chav tsev kub tuaj yeem txo qis qee qhov kev cuam tshuam rau kev ntxhov siab txias, uas tuaj yeem hu rau cov lus nug txog kev hloov pauv ntawm cov ntaub ntawv nas rau tib neeg.Txawm li cas los xij, nws tsis paub meej tias qhov ntsuas kub zoo li cas rau kev khaws nas kom ua raws li tib neeg lub cev.Cov lus teb rau lo lus nug no kuj tuaj yeem cuam tshuam los ntawm kev kawm thiab qhov kawg ntawm kev kawm.Ib qho piv txwv ntawm qhov no yog qhov cuam tshuam ntawm kev noj zaub mov ntawm daim siab rog ntau ntxiv, qabzib kam rau siab thiab insulin tsis kam19.Hais txog kev siv hluav taws xob, qee cov kws tshawb fawb ntseeg tias thermoneutrality yog qhov zoo tshaj plaws kub rau kev yug me nyuam, vim tib neeg xav tau lub zog ntxiv me ntsis los tswj lawv lub cev kub, thiab lawv txhais tau tias qhov kub ntawm ib leeg rau cov nas laus li 30 ° C7,10.Lwm cov kws tshawb fawb ntseeg tias qhov ntsuas kub piv rau tib neeg feem ntau ntsib nrog cov nas laus ntawm ib lub hauv caug yog 23-25 ° C, raws li lawv pom qhov ntsuas kub ntawm 26-28 ° C thiab raws li tib neeg qis dua 3 ° C.Lawv qhov ntsuas kub qis dua, txhais ntawm no yog 23 ° C, yog me ntsis 8.12.Peb txoj kev tshawb fawb tau ua raws li ob peb lwm cov kev tshawb fawb uas hais tias qhov ntsuas kub tsis tau ua tiav ntawm 26-28 ° C4, 7, 10, 11, 24, 25, qhia tias 23-25 ° C tsawg dhau.Lwm qhov tseem ceeb uas yuav tsum tau xav txog hauv chav tsev kub thiab thermoneutrality hauv nas yog cov vaj tsev nyob ib leeg lossis pab pawg.Thaum cov nas tau nyob hauv pab pawg tsis yog ib tus zuj zus, ib yam li hauv peb txoj kev tshawb fawb, qhov kub thiab txias tau txo qis, tej zaum yog vim muaj cov tsiaj txhu coob coob.Txawm li cas los xij, chav tsev kub tseem qis dua LTL ntawm 25 thaum siv peb pawg.Tej zaum qhov sib txawv tseem ceeb tshaj plaws hauv qhov no yog qhov tseem ceeb ntawm BAT kev ua si raws li kev tiv thaiv hypothermia.Yog li, thaum cov nas tau them nyiaj ntau dua rau lawv cov calories ntau dua los ntawm kev nce BAT kev ua si, uas yog ntau dua 60% EE ntawm 5 ° C ib leeg, 51,52 qhov kev koom tes ntawm tib neeg BAT kev ua si rau EE tau ntau dua, me dua.Yog li ntawd, txo qis kev ua BAT tej zaum yuav yog ib txoj hauv kev tseem ceeb los ua kom tib neeg txhais lus.Kev tswj hwm ntawm BAT kev ua haujlwm yog qhov nyuaj tab sis feem ntau kho los ntawm kev sib koom ua ke ntawm adrenergic stimulation, thyroid hormones thiab UCP114,54,55,56,57 qhia.Peb cov ntaub ntawv qhia tias qhov kub thiab txias yuav tsum tau nce siab tshaj 27.5 ° C piv rau cov nas ntawm 22 ° C txhawm rau txhawm rau txhawm rau txheeb xyuas qhov sib txawv ntawm kev qhia ntawm BAT noob lub luag haujlwm rau kev ua haujlwm / ua kom muaj zog.Txawm li cas los xij, qhov sib txawv ntawm cov pab pawg ntawm 30 thiab 22 ° C tsis yog ib txwm qhia tias muaj kev nce hauv BAT hauv pawg 22 ° C vim tias Ucp1, Adrb2 thiab Vegf-a tau txo qis hauv pawg 22 ° C.Lub hauv paus ua rau cov txiaj ntsig tsis tau xav txog tseem yuav raug txiav txim siab.Ib qho muaj peev xwm yog tias lawv cov lus qhia nce ntxiv yuav tsis cuam tshuam qhov teeb meem ntawm qhov kub siab hauv chav tsev, tab sis qhov tshwm sim ntawm kev txav ntawm 30 ° C mus rau 22 ° C nyob rau hnub tshem tawm (cov nas tau ntsib qhov no 5-10 feeb ua ntej tawm mus) .).
Ib qho kev txwv dav dav ntawm peb txoj kev tshawb fawb yog tias peb tsuas yog kawm txiv neej nas.Lwm qhov kev tshawb fawb qhia tias poj niam los txiv neej yuav yog ib qho tseem ceeb hauv peb cov kev qhia tseem ceeb, vim tias ib leeg-pob poj niam nas muaj qhov kub thiab txias dua vim muaj thermal conductivity ntau dua thiab tswj kom nruj dua cov tub ntxhais kub.Tsis tas li ntawd, cov nas poj niam (ntawm HFD) tau pom tias muaj kev sib koom ua ke ntau dua ntawm kev siv lub zog nrog EE ntawm 30 ° C piv rau cov nas txiv neej uas tau noj cov nas ntau dua ntawm tib poj niam txiv neej (20 ° C hauv qhov no) 20 .Yog li, nyob rau hauv poj niam nas, cov nyhuv subthermonetral cov ntsiab lus yog siab dua, tab sis muaj cov qauv zoo ib yam li txiv neej nas.Hauv peb txoj kev tshawb fawb, peb tsom mus rau ib leeg-lub hauv caug txiv neej nas, vim tias cov no yog cov xwm txheej uas feem ntau ntawm cov kev tshawb fawb metabolic kuaj EE tau ua.Lwm qhov kev txwv ntawm peb txoj kev tshawb fawb yog cov nas nyob rau tib qho kev noj haus thoob plaws hauv txoj kev tshawb no, uas tau txwv tsis pub kawm qhov tseem ceeb ntawm chav tsev kub rau metabolic yooj (raws li ntsuas los ntawm RER kev hloov pauv rau kev noj haus hauv ntau yam macronutrient compositions).Nyob rau hauv cov poj niam thiab txiv neej nas khaws cia ntawm 20 ° C piv rau cov nas coj mus khaws cia ntawm 30 ° C.
Hauv kev xaus, peb txoj kev tshawb fawb qhia tau hais tias, ib yam li lwm cov kev tshawb fawb, lap 1 ib txwm hnyav nas yog thermoneutral tshaj qhov kwv yees 27.5 ° C.Tsis tas li ntawd, peb txoj kev tshawb fawb qhia tau hais tias kev rog rog tsis yog qhov tseem ceeb hauv cov nas uas muaj qhov hnyav lossis DIO, ua rau muaj qhov kub thiab txias: EE ratios hauv DIO thiab cov nas qhov hnyav.Thaum cov zaub mov noj ntawm cov nas hnyav ib txwm ua tau raws li EE thiab yog li tuav lub cev hnyav ntawm tag nrho qhov kub thiab txias, cov khoom noj ntawm DIO nas yog tib yam ntawm qhov kub sib txawv, ua rau cov nas ntau dua ntawm 30 ° C. .ntawm 22 ° C nce ntau lub cev hnyav.Zuag qhia tag nrho, cov kev tshawb fawb soj ntsuam xyuas qhov tseem ceeb ntawm kev ua neej nyob hauv qab qhov kub thiab txias tau lees paub vim tias feem ntau pom tsis zoo ntawm cov nas thiab tib neeg kev tshawb fawb.Piv txwv li, hauv kev tshawb fawb txog kev rog rog, ib feem piav qhia txog qhov kev txhais lus tsis zoo feem ntau yuav yog vim qhov tseeb tias murine poob kev tshawb fawb feem ntau ua rau cov tsiaj mob khaub thuas txias txias nyob rau hauv chav tsev kub vim lawv nce EE.Exaggerated poob phaus piv rau qhov xav tau lub cev hnyav ntawm ib tug neeg, tshwj xeeb tshaj yog tias cov txheej txheem ntawm kev ua yog nyob ntawm kev nce EE los ntawm kev ua kom cov BAP ua haujlwm ntau dua thiab ua kom muaj zog ntawm chav tsev kub dua li ntawm 30 ° C.
Raws li txoj cai Danish Animal Experimental Law (1987) thiab National Institutes of Health (Publication No. 85-23) thiab European Convention for the Protection of Vertebrate use for Experimental and other Scientific Purposes (Council of Europe No. 123, Strasbourg Ib., 1985).
Nees nkaum lub lis piam txiv neej C57BL / 6J nas tau txais los ntawm Janvier Saint Berthevin Cedex, Fabkis, thiab tau muab ad libitum standard chow (Altromin 1324) thiab dej (~ 22 ° C) tom qab 12: 12 teev lub teeb: tsaus ntuj.chav kub.Txiv neej DIO nas (20 lub lis piam) tau txais los ntawm tib lub chaw muag khoom thiab tau txais ad libitum nkag mus rau 45% kev noj zaub mov muaj roj ntau (Cat. No. D12451, Research Diet Inc., NJ, USA) thiab dej hauv qab kev yug me nyuam.Cov nas tau yoog rau ib puag ncig ib lub lis piam ua ntej pib txoj kev kawm.Ob hnub ua ntej hloov mus rau qhov tsis ncaj calorimetry system, nas tau hnyav, raug MRI scanning (EchoMRITM, TX, USA) thiab muab faib ua plaub pawg sib luag rau lub cev hnyav, rog thiab lub cev hnyav.
Daim duab kos duab ntawm txoj kev tshawb fawb tsim tau pom nyob rau hauv daim duab 8. Cov nas raug xa mus rau qhov kaw thiab tswj qhov kub thiab txias tsis ncaj calorimetry system ntawm Sable Systems Internationals (Nevada, USA), uas suav nrog cov zaub mov thiab dej zoo saib xyuas thiab Promethion BZ1 ncej uas tau sau tseg. theem kev ua si los ntawm kev ntsuas cov nqaj tawg.XYZ.Cov nas (n = 8) tau nyob ib leeg ntawm 22, 25, 27.5, lossis 30 ° C siv cov txaj pw tab sis tsis muaj vaj tse thiab cov khoom zes ntawm 12: 12-teev lub teeb: tsaus ntuj (lub teeb: 06:00–18:00) .2500ml / minCov nas tau acclimatized rau 7 hnub ua ntej sau npe.Cov ntaub ntawv kaw tau raug sau plaub hnub ua ke.Tom qab ntawd, cov nas tau khaws cia ntawm qhov kub ntawm 25, 27.5, thiab 30 ° C rau 12 hnub ntxiv, tom qab ntawd cov cell concentrates tau ntxiv raws li tau piav qhia hauv qab no.Lub caij no, pab pawg nas khaws cia ntawm 22 ° C tau khaws cia ntawm qhov kub no rau ob hnub ntxiv (kom khaws cov ntaub ntawv hauv paus tshiab), thiab tom qab ntawd qhov kub thiab txias tau nce hauv qib ntawm 2 ° C txhua hnub thaum pib ntawm lub teeb theem ( 06:00) kom txog rau thaum nce mus txog 30 ° C Tom qab ntawd, qhov kub thiab txias tau qis rau 22 ° C thiab cov ntaub ntawv tau muab khaws cia rau ob hnub ntxiv.Tom qab ob hnub ntxiv ntawm kev kaw cia ntawm 22 ° C, cov tawv nqaij tau ntxiv rau txhua lub hlwb ntawm txhua qhov kub, thiab kev sau cov ntaub ntawv pib rau hnub ob (hnub 17) thiab rau peb hnub.Tom qab ntawd (hnub 20), cov khoom siv zes (8-10 g) tau ntxiv rau tag nrho cov hlwb thaum pib lub teeb lub voj voog (06:00) thiab cov ntaub ntawv tau sau rau lwm peb hnub.Yog li, thaum kawg ntawm txoj kev tshawb no, nas nyob rau ntawm 22 ° C tau khaws cia ntawm qhov kub no rau 21/33 hnub thiab ntawm 22 ° C rau 8 hnub kawg, thaum nas ntawm lwm qhov kub tau khaws cia ntawm qhov kub no rau 33 hnub./ 33 hnub.Cov nas tau noj thaum lub sijhawm kawm.
Qhov hnyav li qub thiab DIO nas ua raws li cov txheej txheem kev kawm tib yam.Nyob rau hnub -9, nas tau hnyav, MRI scanned, thiab muab faib ua pawg piv rau lub cev hnyav thiab lub cev muaj pes tsawg leeg.Hnub -7, cov nas tau pauv mus rau qhov ntsuas kub kaw tsis ncaj qha calorimetry system tsim los ntawm SABLE Systems International (Nevada, USA).Cov nas tau nyob ib leeg nrog cov txaj tab sis tsis muaj zes lossis cov khoom vaj tse.Qhov kub yog teem rau 22, 25, 27.5 lossis 30 ° C.Tom qab ib lub lim tiam ntawm acclimatization (hnub -7 mus rau 0, tsiaj tsis cuam tshuam), cov ntaub ntawv tau sau rau plaub hnub sib law liag (hnub 0-4, cov ntaub ntawv qhia hauv daim duab 1, 2, 5).Tom qab ntawd, cov nas khaws cia ntawm 25, 27.5 thiab 30 ° C tau khaws cia nyob rau hauv qhov xwm txheej tas mus li mus txog hnub 17th.Nyob rau tib lub sijhawm, qhov kub ntawm 22 ° C pawg tau nce ntawm 2 ° C txhua hnub los ntawm kev kho qhov kub thiab txias (06: 00 h) thaum pib ntawm lub teeb raug (cov ntaub ntawv muaj nyob hauv daim duab 1) .Hnub tim 15, qhov kub tau poob mus rau 22 ° C thiab ob hnub ntawm cov ntaub ntawv tau sau los muab cov ntaub ntawv hauv paus rau kev kho mob tom ntej.Cov tawv nqaij tau ntxiv rau txhua tus nas nyob rau hnub 17, thiab cov khoom siv zes tau ntxiv rau hnub 20 (Fig. 5).Hnub tim 23, cov nas tau hnyav thiab raug kuaj MRI, thiab tom qab ntawd nyob ib leeg rau 24 teev.Hnub 24, cov nas tau yoo mov txij thaum pib lub sijhawm photoperiod (06:00) thiab tau txais OGTT (2 g / kg) thaum 12:00 (6-7 teev yoo mov).Tom qab ntawd, cov nas raug xa rov qab mus rau lawv cov xwm txheej SABLE thiab euthanized rau hnub thib ob (hnub 25).
DIO nas (n = 8) ua raws tib txoj cai raws li cov nas qhov hnyav (raws li tau piav qhia saum toj no thiab hauv daim duab 8).Cov nas tswj hwm 45% HFD thoob plaws hauv kev sim siv hluav taws xob.
VO2 thiab VCO2, nrog rau cov dej vapor siab, tau sau tseg ntawm qhov zaus ntawm 1 Hz nrog lub sijhawm ntawm tes ntawm 2.5 min.Khoom noj khoom haus thiab dej tau txais los ntawm kev sau tseg tas li (1 Hz) ntawm qhov hnyav ntawm cov zaub mov thiab dej ntim.Cov kev soj ntsuam zoo siv tau tshaj tawm qhov kev daws teeb meem ntawm 0.002 g.Cov qib kev ua haujlwm tau sau tseg siv 3D XYZ beam array saib, cov ntaub ntawv tau sau ntawm qhov kev daws teeb meem sab hauv ntawm 240 Hz thiab tshaj tawm txhua thib ob kom suav tag nrho cov kev mus los (m) nrog kev daws teeb meem zoo ntawm 0.25 cm.Cov ntaub ntawv tau ua tiav nrog Sable Systems Macro Interpreter v.2.41, suav nrog EE thiab RER thiab lim tawm cov khoom tawm (xws li cov xwm txheej noj mov cuav).Tus neeg txhais lus macro tau teeb tsa los tso tawm cov ntaub ntawv rau txhua qhov ntsuas txhua tsib feeb.
Ntxiv nrog rau kev tswj hwm EE, qhov ntsuas kub ib puag ncig kuj tseem tuaj yeem tswj hwm lwm yam ntawm cov metabolism, suav nrog postprandial qabzib metabolism, los ntawm kev tswj cov kua qaub-metabolizing cov tshuaj hormones.Txhawm rau ntsuas qhov kev xav no, peb thaum kawg ua tiav qhov kev ntsuas kub ntawm lub cev los ntawm kev ua rau cov nas hnyav hnyav nrog DIO qhov ncauj cov piam thaj load (2 g / kg).Cov txheej txheem tau piav qhia meej hauv cov ntaub ntawv ntxiv.
Thaum kawg ntawm txoj kev tshawb no (hnub 25), nas tau yoo mov rau 2-3 teev (pib thaum 06:00), tshuaj loog nrog isoflurane, thiab los ntshav los ntawm retroorbital venipuncture.Kev ntsuas ntawm cov ntshav lipids thiab cov tshuaj hormones thiab lipids hauv daim siab tau piav qhia hauv Cov Khoom Siv Ntxiv.
Txhawm rau tshawb xyuas seb lub plhaub kub ua rau muaj kev hloov pauv hauv cov ntaub so ntswg adipose cuam tshuam lipolysis, cov ntaub so ntswg inguinal thiab epididymal adipose raug tshem tawm ncaj qha los ntawm cov nas tom qab theem kawg ntawm cov ntshav.Cov ntaub so ntswg tau ua tiav siv qhov kev ntsuam xyuas tshiab ex vivo lipolysis tau piav qhia hauv Cov Txheej Txheem Ntxiv.
Brown adipose cov ntaub so ntswg (BAT) tau sau rau hnub kawg ntawm txoj kev tshawb fawb thiab ua tiav raws li tau piav qhia hauv cov txheej txheem ntxiv.
Cov ntaub ntawv raug nthuav tawm raws li txhais tau tias ± SEM.Graphs tau tsim nyob rau hauv GraphPad Prism 9 (La Jolla, CA) thiab cov duab tau hloov kho hauv Adobe Illustrator (Adobe Systems Incorporated, San Jose, CA).Kev txheeb xyuas qhov tseem ceeb tau raug soj ntsuam hauv GraphPad Prism thiab kuaj los ntawm kev sib tw t-test, rov ntsuas ib-txoj kev / ob-txoj kev ANOVA tom qab los ntawm Tukey ntau qhov kev sib piv, lossis tsis muaj kev sib tw ib-txoj kev ANOVA ua raws li Tukey ntau qhov kev sib piv sib piv raws li xav tau.Gaussian kev faib tawm ntawm cov ntaub ntawv tau lees paub los ntawm D'Agostino-Pearson normality test ua ntej kuaj.Cov qauv loj yog qhia nyob rau hauv qhov sib txuas ntawm ntu "Tsev tau", nrog rau hauv cov lus dab neeg.Repetition yog txhais raws li ib qho kev ntsuas coj los ntawm tib tus tsiaj (hauv vivo lossis ntawm cov ntaub so ntswg).Hais txog cov ntaub ntawv rov tsim dua tshiab, kev sib koom ua ke ntawm kev siv hluav taws xob thiab cov ntaub ntawv kub tau pom nyob rau hauv plaub txoj kev tshawb fawb ywj pheej siv cov nas sib txawv nrog cov qauv kev kawm zoo sib xws.
Cov ncauj lus kom ntxaws txog kev sim, cov ntaub ntawv, thiab cov ntaub ntawv nyoos muaj nyob rau ntawm qhov kev thov tsim nyog los ntawm tus thawj coj sau Rune E. Kuhre.Txoj kev tshawb no tsis tau tsim cov tshuaj reagents tshiab, transgenic tsiaj / cell kab, los yog sequencing cov ntaub ntawv.
Yog xav paub ntxiv txog kev tsim qauv, saib Nature Research Report abstract linked to this article.
Tag nrho cov ntaub ntawv tsim ib daim duab.1-7 tau muab tso rau hauv Science database repository, tus lej nkag: 1253.11.sciencedb.02284 lossis https://doi.org/10.57760/sciencedb.02284.Cov ntaub ntawv qhia hauv ESM yuav raug xa mus rau Rune E Kuhre tom qab kev sim tsim nyog.
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Post lub sij hawm: Oct-28-2022
