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Yawancin nazarin rayuwa a cikin mice ana gudanar da su a cikin zafin jiki, kodayake a ƙarƙashin waɗannan yanayi, ba kamar mutane ba, mice suna ciyar da makamashi mai yawa don kiyaye zafin ciki.Anan, mun bayyana nauyin al'ada da kiba mai haifar da abinci (DIO) a cikin C57BL / 6J mice feedd chow chow ko 45% babban abinci mai mai, bi da bi.An sanya mice na kwanaki 33 a 22, 25, 27.5 da 30 ° C. a cikin tsarin calorimetry kai tsaye.Mun nuna cewa kashe wutar lantarki yana ƙaruwa a layi daya daga 30 ° C zuwa 22 ° C kuma yana da kusan 30% mafi girma a 22 ° C a cikin nau'ikan linzamin kwamfuta biyu.A cikin mice masu nauyi na yau da kullun, cin abinci ya sabawa EE.Sabanin haka, berayen DIO ba su rage cin abinci ba lokacin da EE ya ragu.Don haka, a ƙarshen binciken, beraye a 30 ° C suna da nauyin jiki mafi girma, kitsen mai da plasma glycerol da triglycerides fiye da mice a 22 ° C.Rashin daidaituwa a cikin berayen DIO na iya kasancewa saboda karuwar cin abinci na tushen jin daɗi.
Mouse shine samfurin dabba da aka fi amfani dashi don nazarin ilimin halittar ɗan adam da ilimin halittar jiki, kuma galibi shine dabbar da aka saba amfani da ita a farkon matakan gano magunguna da haɓakawa.Duk da haka, beraye sun bambanta da mutane ta hanyoyi masu mahimmanci na ilimin lissafi, kuma yayin da za'a iya amfani da sikelin allometric zuwa wani matsayi don fassarawa cikin mutane, babban bambance-bambance tsakanin mice da mutane suna kwance a cikin thermoregulation da makamashi homeostasis.Wannan yana nuna rashin daidaituwa na asali.Matsakaicin adadin jikin berayen manya ya kai aƙalla sau dubu ƙasa da na manya (50 g vs. 50 kg), kuma yanayin ƙasa zuwa yawan adadin ya bambanta da kusan sau 400 saboda canjin juzu'i mara misaltuwa wanda Mee ya bayyana. .Equation 2. A sakamakon haka, berayen suna rasa zafi sosai dangane da ƙarar su, don haka sun fi kula da zafin jiki, sun fi dacewa da hypothermia, kuma suna da matsakaicin matsakaicin matsakaicin matsakaici na basal sau goma fiye da na mutane.A daidaitaccen yanayin ɗaki (~ 22°C), beraye dole ne su ƙara yawan kashe kuzarin su (EE) da kusan 30% don kula da ainihin zafin jiki.A ƙananan yanayin zafi, EE yana ƙaruwa da kusan 50% da 100% a 15 da 7°C idan aka kwatanta da EE a 22°C.Don haka, daidaitattun yanayin gidaje suna haifar da amsawar sanyi mai sanyi, wanda zai iya yin lahani ga canja wurin sakamakon linzamin kwamfuta zuwa ga mutane, yayin da mutanen da ke rayuwa a cikin al'ummomin zamani ke ciyar da mafi yawan lokutansu a cikin yanayin zafi (saboda ƙananan yanki na yanki zuwa girma yana sa mu ƙasa da hankali). zafin jiki, yayin da muke ƙirƙirar yankin thermoneutral (TNZ) a kusa da mu EE sama da ƙimar haɓakar basal) ya kai ~ 19 zuwa 30 ° C6, yayin da mice ke da mafi girma da kunkuntar band wanda ke mamaye kawai 2-4 ° C7,8 A zahiri, wannan mahimmanci. Al'amari ya sami kulawa sosai a cikin 'yan shekarun nan4, 7,8,9,10,11,12 kuma an ba da shawarar cewa za a iya rage wasu "bambance-bambancen iri" ta hanyar ƙara yawan zafin jiki na harsashi. wanda ya ƙunshi yanayin zafi a cikin mice.Don haka, ko ƙananan zafin jiki mai mahimmanci a cikin kewayon thermal a cikin berayen gwiwa guda ɗaya ya fi kusa da 25 ° C ko kusa da 30 ° C4, 7, 8, 10, 12 ya kasance mai kawo rigima.EE da sauran sigogi na rayuwa an iyakance su zuwa sa'o'i zuwa kwanaki, don haka iyakar abin da tsayin daka ga yanayin zafi daban-daban zai iya shafar sigogi na rayuwa kamar nauyin jiki ba a sani ba.amfani, amfani da substrate, haƙurin glucose, da lipid plasma da taro na glucose da hormones masu sarrafa ci.Bugu da ƙari, ana buƙatar ƙarin bincike don sanin ko wane irin abinci zai iya rinjayar waɗannan sigogi (mice DIO akan abinci mai kitse na iya zama mafi dacewa ga abinci na tushen jin daɗi (hedonic).Don samar da ƙarin bayani game da wannan batu, mun bincika tasirin yanayin zafin rai akan sigogin rayuwa da aka ambata a cikin berayen maza masu nauyi na yau da kullun da ƙwaya masu kiba (DIO) maza waɗanda ke haifar da abinci akan abinci mai mai 45%.An ajiye beraye a 22, 25, 27.5, ko 30 ° C na akalla makonni uku.Ba a yi nazarin yanayin zafin da ke ƙasa da 22 ° C ba saboda daidaitattun gidajen dabbobi ba su da ƙasa da zafin ɗaki.Mun gano cewa berayen DIO-nauyi na al'ada da da'ira guda ɗaya sun amsa daidai da canje-canje a cikin yanayin kewaye dangane da EE kuma ba tare da la'akari da yanayin rufewa ba (tare da ko ba tare da tsari / kayan gida ba).Koyaya, yayin da ɓeraye masu nauyi na yau da kullun suka daidaita abincin su bisa ga EE, cin abinci na berayen DIO ya kasance mai zaman kansa daga EE, wanda ke haifar da berayen suna samun ƙarin nauyi.Dangane da bayanan nauyin jiki, ƙididdigar plasma na lipids da jikin ketone sun nuna cewa berayen DIO a 30 ° C suna da ma'aunin kuzari mai inganci fiye da beraye a 22 ° C.Dalilan da ke haifar da bambance-bambance a cikin ma'aunin kuzari da kuma EE tsakanin nauyin al'ada da berayen DIO suna buƙatar ƙarin nazari, amma yana iya kasancewa yana da alaƙa da sauye-sauyen pathophysiological a cikin mice DIO da tasirin cin abinci na tushen jin daɗi sakamakon abinci mai ƙiba.
EE ya karu a layi daya daga 30 zuwa 22 ° C kuma ya kasance kusan 30% mafi girma a 22 ° C idan aka kwatanta da 30 ° C (Fig. 1a,b).Matsakaicin musayar numfashi (RER) ya kasance mai zaman kansa daga zafin jiki (Fig. 1c, d).Abincin abinci ya kasance daidai da motsi na EE kuma ya karu tare da rage yawan zafin jiki (kuma ~ 30% mafi girma a 22 ° C idan aka kwatanta da 30 ° C (Fig. 1e, f). Ruwan ruwa. Girman girma da matakin aiki bai dogara da zafin jiki ba (Fig. 1g) - ku.
Mice maza (C57BL / 6J, 20 makonni da haihuwa, gidaje na mutum, n = 7) an ajiye su a cikin cages na rayuwa a 22 ° C. na mako guda kafin fara binciken.Kwanaki biyu bayan tattara bayanan baya, an ɗaga zafin jiki a cikin haɓaka 2 ° C a 06: 00 hours a kowace rana (farkon lokacin haske).Ana gabatar da bayanai azaman ma'anar ± daidaitaccen kuskure na ma'ana, kuma lokacin duhu (18: 00-06: 00 h) yana wakilta ta akwatin launin toka.kashe kuzarin makamashi (kcal/h), b Jimlar kashe kuzari a yanayin zafi daban-daban (kcal/24 h), c Adadin musanya na numfashi (VCO2/VO2: 0.7-1.0), d Ma'anar RER a cikin haske da duhu (VCO2 / VO2) lokaci (An kwatanta darajar sifili azaman 0.7).e tarawa abinci ci (g), f 24h jimlar abincin abinci, g 24h jimlar yawan ruwa (ml), h 24h jimlar yawan ruwa, i matakin aikin tarawa (m) da j jimlar matakin aiki (m / 24h).).An ajiye berayen a yanayin zafin da aka nuna na awanni 48.Bayanan da aka nuna don 24, 26, 28 da 30 ° C suna nufin sa'o'i 24 na ƙarshe na kowane zagayowar.An ci gaba da ciyar da berayen a duk tsawon binciken.An gwada mahimmancin ƙididdiga ta hanyar maimaita ma'auni na ANOVA ta hanya ɗaya wanda ke biye da gwajin kwatancen Tukey.Asterisks suna nuna mahimmanci ga ƙimar farko na 22 ° C, shading yana nuna mahimmanci tsakanin sauran ƙungiyoyi kamar yadda aka nuna. 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.An ƙididdige matsakaicin ƙima na tsawon lokacin gwaji (0-192 hours).n = 7.
Kamar yadda yake a cikin mice masu nauyi na al'ada, EE ya karu a layi tare da rage yawan zafin jiki, kuma a cikin wannan yanayin, EE kuma ya kasance kusan 30% mafi girma a 22 ° C idan aka kwatanta da 30 ° C (Fig. 2a,b).RER bai canza ba a yanayin zafi daban-daban (Fig. 2c, d).Ya bambanta da nauyin beraye na yau da kullun, cin abinci bai yi daidai da EE ba azaman yanayin zafin ɗaki.Abincin abinci, shan ruwa, da matakin aiki sun kasance masu zaman kansu daga zafin jiki (Figs. 2e-j).
Namiji (C57BL / 6J, 20 makonni) DIO mice sun kasance daidaiku a cikin cages na rayuwa a 22 ° C. na mako guda kafin fara binciken.Mice na iya amfani da 45% HFD ad libitum.Bayan haɓakawa na kwanaki biyu, an tattara bayanan asali.Daga baya, an ɗaga zafin jiki a cikin ƙarin 2 ° C kowace rana a 06: 00 (farkon lokacin haske).Ana gabatar da bayanai azaman ma'anar ± daidaitaccen kuskure na ma'ana, kuma lokacin duhu (18: 00-06: 00 h) yana wakilta ta akwatin launin toka.kashe kuzarin makamashi (kcal/h), b Jimlar kashe kuzari a yanayin zafi daban-daban (kcal/24 h), c Adadin musanya na numfashi (VCO2/VO2: 0.7-1.0), d Ma'anar RER a cikin haske da duhu (VCO2 / VO2) lokaci (An kwatanta darajar sifili azaman 0.7).e tarawa abinci ci (g), f 24h jimlar abincin abinci, g 24h jimlar yawan ruwa (ml), h 24h jimlar yawan ruwa, i matakin aikin tarawa (m) da j jimlar matakin aiki (m / 24h).).An ajiye berayen a yanayin zafin da aka nuna na awanni 48.Bayanan da aka nuna don 24, 26, 28 da 30 ° C suna nufin sa'o'i 24 na ƙarshe na kowane zagayowar.An kiyaye beraye a 45% HFD har zuwa ƙarshen binciken.An gwada mahimmancin ƙididdiga ta hanyar maimaita ma'auni na ANOVA ta hanya ɗaya wanda ke biye da gwajin kwatancen Tukey.Asterisks suna nuna mahimmanci ga ƙimar farko na 22 ° C, shading yana nuna mahimmanci tsakanin sauran ƙungiyoyi kamar yadda aka nuna. P <0.05, ***P <0.001, ****P <0.0001. P <0.05, ***P <0.001, ****P <0.0001. *R<0,05, ***Р<0,001, ****Р<0,0001. P <0.05, ***P <0.001, ****P <0.0001. P <0.05, *** P <0.001, *** P <0.0001. P <0.05, *** P <0.001, *** P <0.0001. *R<0,05, ***Р<0,001, ****Р<0,0001. P <0.05, ***P <0.001, ****P <0.0001.An ƙididdige matsakaicin ƙima na tsawon lokacin gwaji (0-192 hours).n = 7.
A cikin wani jerin gwaje-gwajen, mun bincika tasirin zafin yanayi akan sigogi iri ɗaya, amma wannan lokacin tsakanin ƙungiyoyin berayen da ake kiyaye su akai-akai a wani yanayin zafi.An raba mice zuwa kungiyoyi hudu don rage girman sauye-sauye na ƙididdiga a cikin ma'ana da daidaitattun daidaituwa na nauyin jiki, mai, da nauyin jiki na al'ada (Fig. 3a-c).Bayan kwanaki 7 na haɓakawa, an rubuta kwanakin 4.5 na EE.EE yana tasiri sosai ta yanayin zafin jiki duka a lokacin hasken rana da dare (Fig. 3d), kuma yana ƙaruwa a layi yayin da yawan zafin jiki ya ragu daga 27.5 ° C zuwa 22 ° C (Fig. 3e).Idan aka kwatanta da sauran ƙungiyoyi, an rage RER na ƙungiyar 25 ° C, kuma babu bambance-bambance tsakanin sauran ƙungiyoyin (Fig. 3f, g).Abincin abinci daidai da tsarin EE ya ƙaru da kusan 30% a 22 ° C idan aka kwatanta da 30 ° C (Fig. 3h, i).Amfani da ruwa da matakan aiki ba su bambanta sosai tsakanin ƙungiyoyi (Fig. 3j, k).Bayyana yanayin zafi daban-daban har zuwa kwanaki 33 bai haifar da bambance-bambance a cikin nauyin jiki ba, daɗaɗɗen nauyi, da kitsen mai tsakanin ƙungiyoyi (Fig. 3n-s), amma ya haifar da raguwa a cikin nau'i na nau'i na kusan 15% idan aka kwatanta da maki mai kai rahoton (Fig. 3n-s).3b, r, c)) da kuma yawan kitsen ya karu fiye da sau 2 (daga ~ 1 g zuwa 2-3 g, Fig. 3c, t, c).Abin takaici, majalisar ministocin 30°C tana da kurakuran daidaitawa kuma ba za ta iya samar da cikakkun bayanan EE da RER ba.
- Nauyin jiki (a), kitse (b) da kitse (c) bayan kwanaki 8 (rana ɗaya kafin canja wurin zuwa tsarin SABLE).d Amfanin makamashi (kcal/h).e Matsakaicin amfani da makamashi (0-108 hours) a yanayin zafi daban-daban (kcal/24 hours).f Rarraba musayar numfashi (RER) (VCO2/VO2).g Ma'anar RER (VCO2/VO2).h Jimillar abin da ake ci (g).Ina nufin cin abinci (g/24 hours).j Jimlar yawan ruwa (ml).k Matsakaicin amfani da ruwa (ml/24h).l Matsayin ayyukan tarawa (m).m Matsakaicin matakin ayyuka (m/24h).n nauyin jiki a rana ta 18, o canza nauyin jiki (daga -8th zuwa 18th day), p lean mass a ranar 18th, q canji a cikin kitse (daga -8th zuwa ranar 18th), r kitsen taro a ranar 18 , da kuma canza yawan kitse (daga -8 zuwa kwanaki 18).An gwada mahimmancin ƙididdiga na matakan maimaitawa ta Oneway-ANOVA tare da gwajin kwatancen Tukey da yawa. 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.Ana gabatar da bayanai azaman ma'ana + daidaitaccen kuskure na ma'ana, lokacin duhu (18: 00-06: 00 h) ana wakilta ta akwatunan launin toka.Dige-dige a kan alkaluman lissafin suna wakiltar mice guda ɗaya.An ƙididdige matsakaicin ƙima na tsawon lokacin gwaji (0-108 hours).n = 7.
An daidaita mice a cikin nauyin jiki, nauyin nauyi, da kitsen mai a asali (Figs. 4a-c) kuma an kiyaye su a 22, 25, 27.5, da 30 ° C kamar yadda a cikin nazarin tare da ƙananan mice na al'ada..Lokacin kwatanta ƙungiyoyin berayen, dangantakar dake tsakanin EE da zafin jiki sun nuna alaƙar layi ɗaya tare da zafin jiki akan lokaci a cikin mice iri ɗaya.Don haka, berayen da aka ajiye a 22°C sun cinye kusan 30% ƙarin kuzari fiye da berayen da aka ajiye a 30°C (Fig. 4d, e).Lokacin nazarin tasirin dabbobi, zazzabi ba koyaushe yana shafar RER (Fig. 4f, g).Abincin abinci, shan ruwa, da aiki ba su da tasiri sosai ta yanayin zafi (Figs. 4h-m).Bayan kwanaki 33 na reno, beraye a 30 ° C suna da nauyin jiki mafi girma fiye da beraye a 22 ° C (Fig. 4n).Idan aka kwatanta da ma'anar tushen su, mice da aka haifa a 30 ° C suna da nauyin nauyin jiki mafi girma fiye da mice da aka haifa a 22 ° C (ma'anar ± kuskuren kuskure na ma'anar: Fig. 4o).Matsakaicin ƙimar mafi girma mafi girma shine saboda haɓakar kitse mai yawa (Fig. 4p, q) maimakon haɓakar ƙima (Fig. 4r, s).Daidaita da ƙananan ƙimar EE a 30 ° C, maganganun ƙwayoyin BAT da yawa waɗanda ke haɓaka aikin / ayyuka na BAT an rage su a 30 ° C idan aka kwatanta da 22 ° C: Adra1a, Adrb3, da Prdm16.Sauran mahimman kwayoyin halittar da ke kara yawan aikin BAT / ayyuka ba su shafi: Sema3a (tsarin ci gaban neurite), Tfam (mitochondrial biogenesis), Adrb1, Adra2a, Pck1 (gluconeogenesis) da Cpt1a.Abin mamaki, Ucp1 da Vegf-a, waɗanda ke da alaƙa da ƙara yawan aikin thermogenic, ba su ragu a cikin ƙungiyar 30 ° C ba.A zahiri, matakan Ucp1 a cikin beraye uku sun fi girma a cikin rukunin 22°C, kuma Vegf-a da Adrb2 sun ɗaukaka sosai.Idan aka kwatanta da ƙungiyar 22 °C, berayen da aka kiyaye a 25 °C da 27.5 °C ba su nuna wani canji ba (Ƙarin Hoto 1).
- Nauyin jiki (a), kitse (b) da kitse (c) bayan kwanaki 9 (rana ɗaya kafin canja wurin zuwa tsarin SABLE).d Amfanin makamashi (EE, kcal/h).e Matsakaicin amfani da makamashi (0-96 hours) a yanayin zafi daban-daban (kcal/24 hours).f Rarraba musayar numfashi (RER, VCO2/VO2).g Ma'anar RER (VCO2/VO2).h Jimillar abin da ake ci (g).Ina nufin cin abinci (g/24 hours).j Jimlar yawan ruwa (ml).k Matsakaicin amfani da ruwa (ml/24h).l Matsayin ayyukan tarawa (m).m Matsakaicin matakin ayyuka (m/24h).n Nauyin jiki a rana ta 23 (g), o Canjin nauyin jiki, p Lean taro, q Canji a cikin kitse (g) a rana ta 23 idan aka kwatanta da ranar 9, Canjin kitse (g) a ranar 23, mai. taro (g) idan aka kwatanta da ranar 8, ranar 23 idan aka kwatanta da -8th day.An gwada mahimmancin ƙididdiga na matakan maimaitawa ta Oneway-ANOVA tare da gwajin kwatancen Tukey da yawa. P <0.05, ***P <0.001, ****P <0.0001. P <0.05, ***P <0.001, ****P <0.0001. *R<0,05, ***Р<0,001, ****Р<0,0001. P <0.05, ***P <0.001, ****P <0.0001. P <0.05, *** P <0.001, *** P <0.0001. P <0.05, *** P <0.001, *** P <0.0001. *R<0,05, ***Р<0,001, ****Р<0,0001. P <0.05, ***P <0.001, ****P <0.0001.Ana gabatar da bayanai azaman ma'ana + daidaitaccen kuskure na ma'ana, lokacin duhu (18: 00-06: 00 h) ana wakilta ta akwatunan launin toka.Dige-dige a kan alkaluman lissafin suna wakiltar mice guda ɗaya.An ƙididdige ƙimar ma'ana don duk lokacin gwaji (0-96 hours).n = 7.
Kamar mutane, beraye sukan haifar da ƙananan mahalli don rage asarar zafi ga muhalli.Don ƙididdige mahimmancin wannan yanayin don EE, mun kimanta EE a 22, 25, 27.5, da 30 ° C, tare da ko ba tare da masu gadin fata da kayan gida ba.A 22 ° C, ƙari na daidaitattun fatun yana rage EE da kusan 4%.Ƙarin ƙari na kayan gida na gaba ya rage EE da 3-4% (Fig. 5a,b).Babu wani canje-canje masu mahimmanci a cikin RER, cin abinci, shan ruwa, ko matakan ayyuka da aka lura tare da ƙari na gidaje ko fatun + kwanciya (Hoto 5i-p).Bugu da ƙari na fata da kayan gida kuma sun rage EE sosai a 25 da 30 ° C, amma amsoshin sun kasance ƙanƙanta.A 27.5 ° C ba a sami bambanci ba.Musamman ma, a cikin waɗannan gwaje-gwajen, EE ya rage tare da yawan zafin jiki, a cikin wannan yanayin game da 57% ƙasa da EE a 30 ° C idan aka kwatanta da 22 ° C (Fig. 5c-h).An gudanar da bincike iri ɗaya ne kawai don lokacin haske, inda EE ya fi kusa da basal na rayuwa, tun da yake a cikin wannan yanayin, mice mafi yawa sun huta a cikin fata, wanda ya haifar da girman tasiri mai kama da yanayin zafi daban-daban (Ƙarin Fig. 2a-h). .
Bayanai na beraye daga matsuguni da kayan gida (duhu shuɗi), gida amma babu kayan gida (shuɗi mai haske), da kayan gida da na gida (orange).Amfanin makamashi (EE, kcal/h) don ɗakuna a, c, e da g a 22, 25, 27.5 da 30 ° C, b, d, f da h na nufin EE (kcal/h).ip Data ga berayen da aka ajiye a 22 ° C: i ƙimar numfashi (RER, VCO2 / VO2), j yana nufin RER (VCO2 / VO2), k ci abinci mai tarawa (g), l matsakaicin abinci (g / 24 h) , m jimlar yawan ruwa (mL), n matsakaiciyar ruwa AUC (mL / 24h), o jimlar aiki (m), p matsakaicin matakin aiki (m / 24h).Ana gabatar da bayanai azaman ma'ana + daidaitaccen kuskure na ma'ana, lokacin duhu (18: 00-06: 00 h) ana wakilta ta akwatunan launin toka.Dige-dige a kan alkaluman lissafin suna wakiltar mice guda ɗaya.An gwada mahimmancin ƙididdiga na matakan maimaitawa ta Oneway-ANOVA tare da gwajin kwatancen Tukey da yawa. P <0.05, **P <0.01. P <0.05, **P <0.01. *R<0,05, **Р<0,01. P <0.05, **P <0.01. P <0.05, *** P <0.01. P <0.05, *** P <0.01. *R<0,05, **Р<0,01. P <0.05, **P <0.01.An ƙididdige matsakaicin ƙima na tsawon lokacin gwaji (0-72 hours).n = 7.
A cikin mice masu nauyi na al'ada (2-3 hours na azumi), reno a yanayin zafi daban-daban bai haifar da bambance-bambance masu yawa a cikin ƙwayar plasma na TG, 3-HB, cholesterol, ALT, da AST ba, amma HDL a matsayin aikin zafin jiki.Hoto na 6 a-e).Matsalolin plasma masu azumi na leptin, insulin, C-peptide, da glucagon suma basu bambanta tsakanin ƙungiyoyi ba (Figures 6g-j).A ranar gwajin haƙuri na glucose (bayan kwanaki 31 a yanayin zafi daban-daban), matakin glucose na asali (sa'o'i 5-6 na azumi) ya kasance kusan 6.5 mM, ba tare da bambanci tsakanin ƙungiyoyi ba. Gudanar da glucose na baka yana ƙara yawan adadin glucose na jini a cikin kowane rukuni, amma duka mafi girman maida hankali da yanki na ƙarawa a ƙarƙashin masu lanƙwasa (iAUCs) (15-120 min) sun kasance ƙasa a cikin rukunin berayen da aka ajiye a 30 ° C (makinin lokaci na mutum: P). <0.05-P <0.0001, siffa 6k, l) idan aka kwatanta da mice da aka ajiye a 22, 25 da 27.5 ° C (wanda bai bambanta da juna ba). Gudanar da glucose na baka yana ƙara yawan adadin glucose na jini a cikin kowane rukuni, amma duka mafi girman maida hankali da yanki na ƙarawa a ƙarƙashin masu lanƙwasa (iAUCs) (15-120 min) sun kasance ƙasa a cikin rukunin berayen da aka ajiye a 30 ° C (makinin lokaci na mutum: P). <0.05-P <0.0001, Fig. 6k, l) idan aka kwatanta da mice da aka ajiye a 22, 25 da 27.5 ° C (wanda bai bambanta tsakanin juna ba). »Ероралюведе вседлие значиКра Сотовыропо Коповерло Коповерло Коповентело Еирадь Под кым в приносялые врупей, отдей, отдей, отдей, отдей, отдей мышей : P <0,05-P <0,0001, рис. 6k, l) по сравнению мышами, содержащимися при 22, 25 da 27,5 ° C. Gudanar da glucose na baki yana haɓaka yawan adadin glucose na jini a cikin duk ƙungiyoyi, amma duka mafi girman maida hankali da yanki na haɓaka a ƙarƙashin masu lanƙwasa (iAUC) (15-120 min) sun kasance ƙasa da ƙasa a cikin rukunin berayen 30 ° C (maɓallin lokaci daban: P <0.05-). P <0.0001, siffa 6k, l) idan aka kwatanta da mice da aka ajiye a 22, 25 da 27.5 ° C (wanda bai bambanta da juna ba).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)口服 葡萄糖 的 给 了 所有组下 增加 面积 面积 (IAUC) (15-120 分钟) 均 较 低 各 个 点 点点 点: P <0.05–P <0.0001,图6k,l)与饲养在22,25和27.5°C 的小鼠(彼此之没有宛Gudanar da glucose na baka yana haɓaka yawan adadin glucose na jini a cikin kowane rukuni, amma duka mafi girman maida hankali da yanki a ƙarƙashin lanƙwasa (iAUC) (15-120 min) sun kasance ƙasa da ƙasa a cikin rukunin berayen masu ciyar da 30°C (duk lokacin maki).: P <0,05–P <0,0001, рис. : P <0.05-P <0.0001, Hoto.6l, l) idan aka kwatanta da berayen da aka ajiye a 22, 25 da 27.5 ° C (babu bambanci da juna).
Matsalolin Plasma na TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, da glucagon ana nuna su a cikin mice DIO (al) balagaggu na mice bayan kwanaki 33 na ciyarwa a yanayin zafin da aka nuna. .Ba a ciyar da beraye 2-3 hours kafin samfurin jini.Banda shi ne gwajin haƙuri na glucose na baka, wanda aka yi kwanaki biyu kafin ƙarshen binciken akan berayen sun yi azumi na sa'o'i 5-6 kuma ana kiyaye su a yanayin da ya dace na kwanaki 31.An ƙalubalanci beraye da nauyin 2 g/kg.Yankin da ke ƙarƙashin bayanan lanƙwasa (L) an bayyana shi azaman ƙarin bayanai (iAUC).Ana gabatar da bayanai azaman ma'ana ± SEM.Dige-dige suna wakiltar samfuran mutum ɗaya. 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.
A cikin berayen DIO (kuma sun yi azumi na sa'o'i 2-3), ƙwayar cholesterol na plasma, HDL, ALT, AST, da FFA ba su bambanta tsakanin ƙungiyoyi ba.Dukansu TG da glycerol sun haɓaka sosai a cikin ƙungiyar 30 ° C idan aka kwatanta da ƙungiyar 22 ° C (Figures 7a-h).Sabanin haka, 3-GB ya kasance kusan 25% ƙasa a 30°C idan aka kwatanta da 22°C (Hoto 7b).Don haka, ko da yake berayen da aka kiyaye a 22 ° C suna da ma'auni mai kyau na makamashi gaba ɗaya, kamar yadda aka nuna ta hanyar samun nauyi, bambance-bambance a cikin ƙwayar plasma na TG, glycerol, da 3-HB suna ba da shawarar cewa mice a 22 ° C lokacin da samfurin ya kasance ƙasa da 22 °. C.°C.Berayen da aka reno a zafin jiki na 30 ° C sun kasance cikin yanayi mara kyau da kuzari.Daidai da wannan, ƙididdigar hanta na glycerol da TG, amma ba glycogen da cholesterol ba, sun kasance mafi girma a cikin ƙungiyar 30 ° C (Ƙarin Hoto 3a-d).Don bincika ko bambance-bambancen da ke dogara da zafin jiki a cikin lipolysis (kamar yadda aka auna ta plasma TG da glycerol) sune sakamakon canje-canje na ciki a cikin epididymal ko mai inguinal, mun fitar da nama mai adipose daga waɗannan shagunan a ƙarshen binciken kuma mun ƙididdige fatty acid ex. vivo.da kuma sakin glycerol.A cikin dukkanin ƙungiyoyin gwaji, samfurori na adipose nama daga epididymal da inguinal depots sun nuna akalla sau biyu a cikin glycerol da samar da FFA don mayar da martani ga haɓakawar isoproterenol (Ƙarin Hoton 4a-d).Duk da haka, babu wani tasiri na harsashi a kan basal ko isoproterenol-stimulated lipolysis da aka samu.Daidai da girman nauyin jiki da kitsen mai, matakan leptin na plasma sun fi girma a cikin ƙungiyar 30 ° C fiye da ƙungiyar 22 ° C (Hoto 7i).Akasin haka, matakan plasma na insulin da C-peptide ba su bambanta tsakanin ƙungiyoyin zafin jiki ba (Fig. 7k, k), amma plasma glucagon ya nuna dogara ga zafin jiki, amma a wannan yanayin kusan 22 ° C a cikin kishiyar rukunin an kwatanta sau biyu. zuwa 30 ° C.DAGARukunin C (Fig. 7l).FGF21 bai bambanta tsakanin ƙungiyoyin zafin jiki daban-daban ba (Fig. 7m).A ranar OGTT, matakin glucose na jini ya kasance kusan 10 mM kuma bai bambanta tsakanin berayen da aka ajiye a yanayin zafi daban-daban (Fig. 7n).Gudanar da glucose ta baki yana haɓaka matakan glucose na jini kuma ya kai kololuwa a cikin kowane rukuni a kusan 18 mM mintuna 15 bayan allura.Babu wani bambance-bambance masu mahimmanci a cikin iAUC (15-120 min) da ƙididdiga a lokuta daban-daban bayan kashi (15, 30, 60, 90 da 120 min) (Hoto 7n, o).
Matsakaicin Plasma na TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, glucagon, da FGF21 an nuna su a cikin berayen DIO (ao) na manya bayan kwanaki 33 na ciyarwa.ƙayyadadden zafin jiki.Ba a ciyar da beraye 2-3 hours kafin samfurin jini.Gwajin haƙuri na glucose na baka ya banbanta kamar yadda aka yi shi a kashi na 2 g/kg na nauyin jiki kwana biyu kafin ƙarshen binciken a cikin berayen da aka yi azumi na sa'o'i 5-6 kuma ana kiyaye su a yanayin zafin da ya dace na kwanaki 31.Ana nuna yankin da ke ƙarƙashin bayanan lanƙwasa (o) azaman ƙarin bayanai (iAUC).Ana gabatar da bayanai azaman ma'ana ± SEM.Dige-dige suna wakiltar samfuran mutum ɗaya. 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.
Canja wurin bayanan rodent ga mutane wani lamari ne mai rikitarwa wanda ke taka muhimmiyar rawa wajen fassara mahimmancin abubuwan lura a cikin mahallin binciken ilimin halittar jiki da na magunguna.Don dalilai na tattalin arziki da sauƙaƙe bincike, yawancin beraye ana adana su a cikin zafin jiki a ƙasan yankin zafin jiki, wanda ke haifar da kunna tsarin tsarin ilimin halittar jiki daban-daban waɗanda ke haɓaka ƙimar rayuwa da yuwuwar lalata fassarar9.Don haka, bayyanar da beraye zuwa sanyi na iya sanya berayen da ke jure kiba mai haifar da abinci kuma yana iya hana hyperglycemia a cikin berayen da ake yi wa maganin streptozotocin saboda karuwar jigilar glucose da ba ta dogara da insulin ba.Duk da haka, ba a bayyana ba har zuwa wane tsayin tsayin daka ga yanayin zafi daban-daban (daga daki zuwa thermoneutral) yana shafar makamashi daban-daban na homeostasis na mice masu nauyi na yau da kullun (a kan abinci) da mice DIO (a kan HFD) da sigogi na rayuwa, kazalika da girman. wanda suka sami damar daidaita haɓakar EE tare da haɓakar abincin abinci.Binciken da aka gabatar a cikin wannan labarin yana da nufin kawo haske ga wannan batu.
Mun nuna cewa a cikin berayen manya masu nauyi na yau da kullun da kuma mice DIO na maza, EE yana da alaƙa da yanayin zafi tsakanin 22 da 30°C.Don haka, EE a 22 ° C ya kusan 30% sama da 30 ° C.a cikin nau'ikan linzamin kwamfuta biyu.Koyaya, wani muhimmin bambanci tsakanin berayen nauyi na yau da kullun da mice DIO shine yayin da ɓeraye masu nauyi na yau da kullun suka dace da EE a ƙananan yanayin zafi ta hanyar daidaita abincin da ake ci daidai da haka, cin abinci na mice DIO ya bambanta a matakai daban-daban.Yanayin binciken ya kasance iri ɗaya.Bayan wata daya, berayen DIO da aka ajiye a 30°C sun sami karin nauyin jiki da kitso fiye da berayen da ake ajiye su a 22°C, yayin da mutane na yau da kullun suna kiyaye yanayin zafi iri ɗaya kuma tsawon lokaci guda ba sa haifar da zazzabi.bambancin dogara a cikin nauyin jiki.nauyi beraye.Idan aka kwatanta da yanayin zafi kusa da thermoneutral ko a dakin da zafin jiki, girma a zafin jiki ya haifar da DIO ko mice masu nauyi na yau da kullun akan abinci mai mai yawa amma ba akan abincin linzamin kwamfuta na yau da kullun don samun ƙarancin nauyi ba.jiki.Goyan bayan wasu karatu17,18,19,20,21 amma ba duka22,23 ba.
Ƙimar da ke haifar da ƙananan ƙananan ƙananan don rage hasara mai zafi an yi la'akari da shi don matsawa tsaka tsaki na thermal zuwa hagu8, 12. A cikin bincikenmu, duka ƙari na kayan gida da ɓoye sun rage EE amma bai haifar da tsaka tsaki na thermal har zuwa 28 ° C ba.Don haka, bayananmu ba su goyi bayan cewa ƙananan ƙarancin zafin jiki a cikin ƙwanƙwasa balagaggu guda ɗaya, tare da ko ba tare da gidaje masu wadatar muhalli ba, ya kamata ya zama 26-28 ° C kamar yadda aka nuna 8,12, amma yana tallafawa wasu nazarin da ke nuna yanayin zafi.yanayin zafi na 30 ° C a cikin ƙananan mice7, 10, 24. Don rikitar da al'amura, an nuna alamar thermoneutral a cikin mice ba a tsaye ba a lokacin rana yayin da yake ƙasa a lokacin hutu (haske), mai yiwuwa saboda ƙananan kalori. samarwa a sakamakon aiki da thermogenesis mai haifar da abinci.Don haka, a cikin lokacin haske, ƙananan ma'anar tsaka tsaki na thermal ya juya zuwa ~ 29 ° C, kuma a cikin duhu, ~ 33 ° C25.
A ƙarshe, alaƙar da ke tsakanin zafin yanayi da jimillar yawan amfani da makamashi ana ƙaddara ta hanyar zubar da zafi.A cikin wannan mahallin, ma'auni na sararin samaniya zuwa girma shine muhimmin mahimmanci na yanayin zafi, yana rinjayar duka zafi mai zafi (yankin saman) da kuma samar da zafi (ƙarar).Bugu da ƙari ga sararin samaniya, ana kuma ƙayyade canjin zafi ta hanyar rufi (yawan canjin zafi).A cikin mutane, kitse mai yawa na iya rage hasara mai zafi ta hanyar ƙirƙirar shinge mai rufewa a kusa da harsashi na jiki, kuma an ba da shawarar cewa yawan kitse shima yana da mahimmanci ga yanayin zafin jiki a cikin beraye, yana rage ma'aunin zafi da rage yanayin zafin jiki a ƙasan ma'aunin tsaka tsaki na thermal. lankwasa gangara).yanayin zafi idan aka kwatanta da EE)12.Ba a tsara bincikenmu don tantance wannan alaƙar sakawa kai tsaye ba saboda an tattara bayanan abubuwan da ke jikin jiki kwanaki 9 kafin a tattara bayanan kashe kuzarin kuzari kuma saboda yawan kitse ba shi da kwanciyar hankali a duk binciken.Koyaya, tunda nauyin al'ada da mice DIO suna da 30% ƙananan EE a 30 ° C fiye da a 22 ° C duk da aƙalla bambance-bambancen ninki 5 a cikin kitse mai yawa, bayananmu ba su goyi bayan cewa kiba ya kamata ya samar da rufin asali.factor, aƙalla ba a cikin kewayon zafin da aka bincika ba.Wannan yayi daidai da sauran karatun da aka tsara don bincika wannan4,24.A cikin waɗannan karatun, tasirin insulating na kiba kaɗan ne, amma an gano Jawo don samar da 30-50% na jimlar thermal insulation4,24.Koyaya, a cikin matattun berayen, haɓakar zafin jiki ya karu da kusan 450% nan da nan bayan mutuwa, yana ba da shawarar cewa tasirin insulating na Jawo ya zama dole don hanyoyin ilimin lissafi, gami da vasoconstriction, don aiki.Baya ga bambance-bambancen nau'in nau'in gashi tsakanin beraye da mutane, ƙarancin insulating tasirin kiba a cikin beraye kuma ana iya yin tasiri ta waɗannan la'akari: Abubuwan da ke hana kitsen ɗan adam galibi ana yin sulhu ta hanyar kitse na subcutaneous (kauri)26,27.Yawanci a cikin rodents Kasa da 20% na jimillar kitsen dabba28.Bugu da kari, jimillar kitse mai kitse ba zai zama ma'aunin ma'auni na ma'aunin zafin jiki na mutum ba, kamar yadda aka yi jayayya cewa ingantaccen rufin thermal yana kashewa ta hanyar haɓakar da babu makawa a cikin sararin sama (sabili da haka ƙara yawan zafi) yayin da yawan kitse ke ƙaruwa..
A cikin mice masu nauyi na al'ada, matakan plasma masu azumi na TG, 3-HB, cholesterol, HDL, ALT, da AST ba su canza ba a yanayin zafi daban-daban na kusan makonni 5, mai yiwuwa saboda berayen suna cikin yanayin ma'aunin kuzari.sun kasance iri ɗaya a cikin nauyi da tsarin jiki kamar yadda a ƙarshen binciken.Daidai da kamanni a cikin kitse mai yawa, haka nan babu bambance-bambance a cikin matakan leptin na plasma, ko a cikin insulin azumi, C-peptide, da glucagon.An sami ƙarin sigina a cikin berayen DIO.Kodayake beraye a 22 ° C kuma ba su da ma'auni mara kyau na makamashi gaba ɗaya a cikin wannan yanayin (yayin da suka sami nauyi), a ƙarshen binciken sun fi ƙarancin kuzari idan aka kwatanta da berayen da aka reno a 30 ° C, a cikin yanayi kamar su. high ketones.samar da jiki (3-GB) da raguwa a cikin taro na glycerol da TG a cikin jini.Duk da haka, bambance-bambancen da ke dogara da zafin jiki a cikin lipolysis ba ya bayyana sakamakon canje-canje na ciki a cikin epididymal ko inguinal kit, kamar canje-canje a cikin maganganun adipohormone mai amsa lipase, tun da FFA da glycerol da aka fitar daga kitsen da aka cire daga waɗannan ɗakunan ajiya suna tsakanin Zazzabi. kungiyoyi suna kama da juna.Ko da yake ba mu bincika sautin tausayi ba a cikin binciken na yanzu, wasu sun gano cewa (dangane da bugun zuciya da ma'anar bugun jini) yana da alaka da yanayin zafi a cikin mice kuma yana da kusan ƙasa a 30 ° C fiye da 22 ° C 20% C Don haka, bambance-bambancen da suka dogara da zafin jiki a cikin sautin tausayi na iya taka rawa a cikin lipolysis a cikin bincikenmu, amma tunda haɓakar sautin tausayi yana ƙarfafawa maimakon hana lipolysis, wasu hanyoyin na iya magance wannan raguwar ƙwayoyin beraye.Matsayi mai yuwuwa a cikin rushewar kitsen jiki.Yanayin dakin.Bugu da ƙari, wani ɓangare na tasirin motsa jiki na sautin tausayi akan lipolysis ana yin sulhu a kaikaice ta hanyar hanawar insulin mai ƙarfi, yana nuna tasirin katsewar insulin akan lipolysis30, amma a cikin bincikenmu, insulin plasma azumi da sautin tausayi na C-peptide a yanayin zafi daban-daban. bai isa ya canza lipolysis ba.Madadin haka, mun gano cewa bambance-bambance a matsayin makamashi sune wataƙila babban mai ba da gudummawa ga waɗannan bambance-bambance a cikin berayen DIO.Dalilan da ke haifar da ingantacciyar tsarin cin abinci tare da EE a cikin berayen nauyi na yau da kullun suna buƙatar ƙarin karatu.Gabaɗaya, duk da haka, ana sarrafa cin abinci ta homeostatic da hedonic cues31,32,33.Ko da yake akwai muhawara game da wanne daga cikin alamomin biyu ya fi mahimmanci, 31,32,33 sananne ne cewa cin abinci mai yawa na dogon lokaci yana haifar da ƙarin dabi'ar cin abinci na jin daɗi wanda har zuwa wani lokaci ba shi da alaƙa. homeostasis..- kayyade abincin abinci34,35,36.Don haka, haɓaka halayen ciyarwar hedonic na berayen DIO da aka kula da su tare da 45% HFD na iya zama ɗayan dalilan da ya sa waɗannan berayen ba su daidaita cin abinci tare da EE ba.Abin sha'awa shine, an kuma lura da bambance-bambance a cikin sha'awar abinci da matakan glucose na jini a cikin berayen DIO masu sarrafa zafin jiki, amma ba a cikin mice masu nauyi na al'ada ba.A cikin berayen DIO, matakan leptin na plasma sun karu tare da zazzabi kuma matakan glucagon sun ragu da zazzabi.Matsakaicin yawan zafin jiki na iya rinjayar waɗannan bambance-bambance kai tsaye ya cancanci ƙarin bincike, amma a cikin yanayin leptin, ma'aunin makamashi mara kyau kuma don haka rage yawan kitse a cikin beraye a 22 ° C tabbas ya taka muhimmiyar rawa, kamar yadda yawan kitse da leptin na plasma ya kasance. mai dangantaka sosai37.Koyaya, fassarar siginar glucagon ya fi rikitarwa.Kamar yadda yake tare da insulin, an hana fitowar glucagon da ƙarfi ta hanyar haɓakar sautin tausayi, amma mafi girman sautin tausayi ana hasashen zai kasance a cikin rukunin 22 ° C, wanda ke da mafi girman adadin glucagon na plasma.Insulin shine wani mai ƙarfi mai ƙarfi na glucagon plasma, kuma juriya na insulin da nau'in ciwon sukari na 2 suna da alaƙa da ƙarfi da azumi da postprandial hyperglucagonemia 38,39.Koyaya, berayen DIO a cikin bincikenmu suma ba su da insulin, don haka wannan kuma ba zai iya zama babban dalilin haɓaka siginar glucagon a cikin rukunin 22°C ba.Abubuwan da ke cikin hanta kuma suna da alaƙa da haɓakar ƙwayar glucagon na plasma, hanyoyin da, bi da bi, na iya haɗawa da juriya na glucagon hepatic, raguwar samar da urea, ƙara yawan adadin amino acid da ke zagayawa, da haɓaka amino acid-stimulated glucagon secretion40,41, 42.Koyaya, tunda abubuwan da za'a iya cirewa na glycerol da TG ba su bambanta tsakanin ƙungiyoyin zafin jiki a cikin bincikenmu ba, wannan kuma ba zai iya zama wani abu mai yuwuwar haɓaka yawan adadin plasma a cikin ƙungiyar 22°C ba.Triiodothyronine (T3) yana taka muhimmiyar rawa a cikin ƙimar rayuwa gabaɗaya da farawa na tsaro na rayuwa daga hypothermia43,44.Don haka, ƙaddamar da ƙwayar plasma T3, mai yiwuwa sarrafawa ta hanyar tsaka-tsaki na tsakiya, 45,46 yana ƙaruwa a cikin mice da mutane a ƙarƙashin ƙasa da yanayin yanayin zafi47, ko da yake karuwa a cikin mutane ya fi ƙanƙanta, wanda ya fi dacewa da mice.Wannan ya yi daidai da asarar zafi ga muhalli.Ba mu auna ma'auni na T3 na plasma ba a cikin binciken na yanzu, amma ƙaddamarwa na iya zama ƙasa a cikin ƙungiyar 30 ° C, wanda zai iya bayyana tasirin wannan rukuni akan matakan glucagon na plasma, kamar yadda muka (sabunta Hoto 5a) da sauransu sun nuna cewa. T3 yana haɓaka glucagon plasma ta hanyar dogaro da kashi.An ba da rahoton hormones na thyroid don haifar da magana FGF21 a cikin hanta.Kamar glucagon, ƙwayar plasma FGF21 kuma ya karu tare da matakan plasma T3 (Ƙarin Hoton 5b da Ref. 48), amma idan aka kwatanta da glucagon, FGF21 plasma maida hankali a cikin bincikenmu ba a shafa da zafin jiki ba.Dalilan da ke haifar da wannan bambance-bambancen suna buƙatar ƙarin bincike, amma T3-tukar FGF21 shigar da ya kamata ya faru a mafi girman matakan bayyanar T3 idan aka kwatanta da martanin glucagon da aka lura da T3 (Ƙarin Hoton 5b).
An nuna HFD yana da alaƙa mai ƙarfi tare da ƙarancin haƙuri na glucose da juriya na insulin (alamomi) a cikin berayen da aka reno a 22°C.Duk da haka, HFD ba a haɗa shi da ko dai rashin haƙuri na glucose ko juriya na insulin lokacin girma a cikin yanayin zafi (wanda aka bayyana a nan a matsayin 28 ° C) 19.A cikin bincikenmu, wannan alaƙar ba ta kasance mai kama da ita a cikin berayen DIO ba, amma mice masu nauyi na yau da kullun da aka kiyaye a 30 ° C sun inganta haɓakar glucose sosai.Dalilin wannan bambance-bambancen yana buƙatar ƙarin bincike, amma yana iya rinjayar da gaskiyar cewa berayen DIO a cikin bincikenmu sun kasance masu juriya na insulin, tare da ƙwayar plasma C-peptide mai azumi da kuma adadin insulin 12-20 sau fiye da nauyin nauyin berayen al'ada.kuma a cikin jini a kan komai a ciki.Matsakaicin adadin glucose na kusan 10 mM (kimanin 6 mM a nauyin jiki na yau da kullun), wanda da alama yana barin ƙaramin taga don kowane tasiri mai fa'ida na fallasa yanayin yanayin zafi don haɓaka haƙurin glucose.Abu mai yuwuwa mai rikitarwa shine, saboda dalilai masu amfani, ana aiwatar da OGTT a cikin zafin jiki.Don haka, berayen da ke zaune a yanayin zafi mai girma sun sami ɗan girgiza mai sanyi, wanda zai iya shafar sha/ sharewar glucose.Koyaya, dangane da irin wannan adadin glucose na jini na azumi a cikin ƙungiyoyin zafin jiki daban-daban, canje-canje a yanayin zafi maiyuwa bai yi tasiri sosai ga sakamakon ba.
Kamar yadda aka ambata a baya, kwanan nan an bayyana cewa ƙara yawan zafin jiki na ɗakin yana iya rage wasu halayen sanyi, wanda zai iya haifar da tambaya game da canja wurin bayanan linzamin kwamfuta zuwa mutane.Duk da haka, ba a bayyana mene ne mafi kyawun zafin jiki don kiyaye beraye su kwaikwayi ilimin halittar ɗan adam ba.Amsar wannan tambayar kuma za a iya yin tasiri a fagen nazari da kuma ƙarshen da ake nazarin.Misalin wannan shine tasirin abinci akan tarin kitsen hanta, jurewar insulin19.Dangane da kashe wutar lantarki, wasu masu bincike sun yi imanin cewa thermoneutrality shine mafi kyawun zafin jiki don renon yara, saboda ɗan adam yana buƙatar ƙarin kuzari kaɗan don kula da zafin jikinsu, kuma suna ayyana zafin jiki guda ɗaya ga berayen manya a matsayin 30 ° C7,10.Wasu masu bincike sun yi imanin cewa yanayin zafi mai kama da wanda ɗan adam yawanci ke fuskanta tare da berayen manya akan gwiwa ɗaya shine 23-25 ° C, saboda sun gano yanayin zafi ya kasance 26-28 ° C kuma bisa ga ɗan adam yana ƙasa da 3 ° C.Matsakaicin zafinsu na ƙasa, wanda aka ayyana a nan a matsayin 23°C, ɗan ƙaramin 8.12 ne.Nazarinmu ya yi daidai da wasu nazarin da yawa waɗanda ke nuna cewa ba a samun tsaka tsaki na thermal a 26-28 ° C4, 7, 10, 11, 24, 25, yana nuna cewa 23-25 ° C ya yi ƙasa da ƙasa.Wani muhimmin al'amari da za a yi la'akari game da zafin jiki da zafin jiki a cikin mice shine gidaje ɗaya ko rukuni.Lokacin da aka ajiye beraye a rukuni maimakon ɗaiɗaiku, kamar yadda a cikin bincikenmu, an rage yawan zafin jiki, mai yiwuwa saboda cunkoson dabbobi.Koyaya, zafin dakin har yanzu yana ƙasa da LTL na 25 lokacin da aka yi amfani da ƙungiyoyi uku.Wataƙila mafi mahimmancin bambance-bambancen interspecies a wannan batun shine ƙimar ƙimar ayyukan BAT azaman kariya daga hypothermia.Don haka, yayin da beraye suka fi ramawa don asarar calorie mafi girma ta hanyar haɓaka ayyukan BAT, wanda ya wuce 60% EE a 5 ° C kadai, 51,52 gudunmawar ayyukan BAT na ɗan adam ga EE ya kasance mafi girma, ƙarami.Saboda haka, rage ayyukan BAT na iya zama hanya mai mahimmanci don ƙara fassarar ɗan adam.Tsarin aikin BAT yana da rikitarwa amma sau da yawa ana yin sulhu ta hanyar haɗakar da tasirin adrenergic, hormones na thyroid da UCP114,54,55,56,57 magana.Bayananmu sun nuna cewa zafin jiki yana buƙatar haɓaka sama da 27.5 ° C idan aka kwatanta da beraye a 22 ° C don gano bambance-bambance a cikin maganganun kwayoyin BAT da ke da alhakin aiki / kunnawa.Duk da haka, bambance-bambancen da aka samu tsakanin kungiyoyi a 30 da 22 ° C ba koyaushe suna nuna karuwa a cikin ayyukan BAT a cikin ƙungiyar 22 ° C ba saboda Ucp1, Adrb2 da Vegf-a an rage su a cikin ƙungiyar 22 ° C.Tushen sakamakon waɗannan sakamakon ba zato ba tsammani ya rage.Ɗaya daga cikin yuwuwar ita ce ƙarar maganganun su bazai nuna alamar yanayin zafin daki ba, amma a maimakon haka babban tasiri na motsa su daga 30 ° C zuwa 22 ° C a ranar cire (berayen sun sami wannan minti 5-10 kafin tashi) .).
Iyakar karatunmu gabaɗaya shine cewa mun yi nazarin beraye ne kawai.Wani bincike ya nuna cewa jinsi na iya zama muhimmin abin la'akari a cikin alamunmu na farko, yayin da ƙwanƙwasa mata guda ɗaya sun fi kula da zafin jiki saboda haɓakar yanayin zafi da kuma kiyaye yanayin zafi mai ƙarfi.Bugu da ƙari, ƙananan mata (a kan HFD) sun nuna babban haɗin gwiwa na cin abinci na makamashi tare da EE a 30 ° C idan aka kwatanta da ƙwararrun maza waɗanda suka cinye yawancin mice na jinsi guda (20 ° C a cikin wannan yanayin) 20.Don haka, a cikin mice na mata, tasirin subthermonetral abun ciki ya fi girma, amma yana da tsari iri ɗaya kamar na mice maza.A cikin bincikenmu, mun mayar da hankali kan mice maza na gwiwa guda ɗaya, kamar yadda waɗannan su ne yanayin da yawancin nazarin rayuwa na nazarin EE ke gudanar da su.Wani ƙayyadaddun bincikenmu shine cewa berayen sun kasance a kan abinci iri ɗaya a duk lokacin binciken, wanda ya hana yin nazarin mahimmancin zafin jiki don sassaucin ra'ayi (kamar yadda aka auna ta RER canje-canje don canje-canje na abinci a cikin nau'o'in macronutrient daban-daban).a cikin berayen mata da na miji ana kiyaye su a 20°C idan aka kwatanta da daidaitattun berayen da aka ajiye su a 30°C.
A ƙarshe, bincikenmu ya nuna cewa, kamar yadda a cikin sauran nazarin, ƙwanƙwasa 1 na al'ada na al'ada suna da zafi sama da 27.5 ° C da aka annabta.Bugu da kari, bincikenmu ya nuna cewa kiba ba shine babban abin rufe fuska ba a cikin beraye masu nauyi na yau da kullun ko DIO, wanda ke haifar da irin wannan zafin jiki: ƙimar EE a cikin DIO da mice masu nauyi na yau da kullun.Duk da yake cin abinci na mice masu nauyi na yau da kullun ya yi daidai da EE kuma don haka ya ci gaba da daidaita nauyin jiki akan duk yanayin zafin jiki, abincin da ake ci na berayen DIO iri ɗaya ne a yanayin zafi daban-daban, wanda ya haifar da ƙimar mice mafi girma a 30 ° C. .a 22 ° C ya sami karin nauyin jiki.Gabaɗaya, nazarin tsarin da ke bincika yuwuwar mahimmancin rayuwa a ƙasa da yanayin zafi yana da garantin saboda yawancin rashin haƙuri da ake gani tsakanin linzamin kwamfuta da nazarin ɗan adam.Misali, a cikin karatun kiba, bayani na juzu'i na fassarori gabaɗaya matalauta na iya kasancewa saboda gaskiyar cewa ana yin nazarin asarar nauyin murine akan dabbobi masu matsananciyar sanyi da aka ajiye a zafin daki saboda karuwar EE.Ƙunƙarar ƙarancin nauyi idan aka kwatanta da nauyin jikin mutum da ake tsammani, musamman idan tsarin aikin ya dogara ne akan ƙara EE ta hanyar ƙara yawan aikin BAP, wanda ya fi aiki kuma yana kunnawa a dakin da zafin jiki fiye da 30 ° C.
Daidai da Dalilin gwajin dabba na Dan dabba (1987) da kuma cibiyoyin Nationalasar Lafiya (Littattafai A'a 85) da kuma babban taron Turai don kariya da aka yi amfani da shi don gwaji da sauran dalilan kimiyyar kimiyya (Majalisar Turai ba 123, Strasbourg , 1985).
An samo berayen C57BL/6J mai mako ashirin daga Janvier Saint Berthevin Cedex, Faransa, kuma an ba su ad libitum standard chow (Altromin 1324) da ruwa (~ 22°C) bayan hasken sa'o'i 12:12: zagayowar duhu.zafin dakin.An samo mice DIO na maza (makonni 20) daga mai sayarwa iri ɗaya kuma an ba su ad libitum damar yin amfani da abinci mai yawa na 45% (Cat. No. D12451, Research Diet Inc., NJ, USA) da ruwa a ƙarƙashin yanayin reno.An daidaita beraye zuwa yanayin mako guda kafin fara binciken.Kwanaki biyu kafin canja wurin zuwa tsarin calorimetry na kai tsaye, an auna mice, an yi amfani da MRI scanning (EchoMRITM, TX, Amurka) kuma an raba su zuwa kungiyoyi hudu masu dacewa da nauyin jiki, mai da nauyin jiki na al'ada.
An nuna zane-zane na zane-zane na binciken a cikin Hoto 8. An canza mice zuwa tsarin rufaffiyar tsarin calorimetry kai tsaye da ke sarrafa zafin jiki a Sable Systems Internationals (Nevada, Amurka), wanda ya haɗa da masu kula da ingancin abinci da ruwa da kuma tsarin Promethion BZ1 wanda ya rubuta. matakan ayyuka ta hanyar auna karyewar katako.XYZ.Mice (n = 8) an ajiye su daban-daban a 22, 25, 27.5, ko 30 ° C ta amfani da kayan kwanciya amma babu tsari da kayan gida akan hasken 12:12-hour: yanayin duhu (haske: 06:00-18:00) .2500ml/min.An haɓaka beraye na kwanaki 7 kafin rajista.An tattara faifan bidiyo kwanaki huɗu a jere.Bayan haka, an ajiye beraye a yanayin zafi daban-daban a 25, 27.5, da 30 ° C don ƙarin kwanaki 12, bayan haka an ƙara tantanin halitta kamar yadda aka bayyana a ƙasa.A halin yanzu, ƙungiyoyin berayen da aka ajiye a 22 ° C an ajiye su a wannan zafin jiki na tsawon kwanaki biyu (don tattara sabbin bayanan asali), sannan kuma ana ƙara yawan zafin jiki a matakai na 2 ° C kowace rana a farkon lokacin haske. 06:00) har sai da ya kai 30 ° C Bayan haka, an rage zafin jiki zuwa 22 ° C kuma an tattara bayanai na wasu kwanaki biyu.Bayan ƙarin kwanaki biyu na rikodi a 22 ° C, an ƙara fatun zuwa duk sel a duk yanayin zafi, kuma an fara tattara bayanai a rana ta biyu (rana 17) da kuma kwanaki uku.Bayan haka (rana 20), an ƙara kayan gida (8-10 g) zuwa duk sel a farkon zagayowar haske (06:00) kuma an tattara bayanai har tsawon kwanaki uku.Don haka, a ƙarshen binciken, an ajiye beraye a zafin jiki na 22 ° C a wannan zafin jiki na kwanaki 21/33 da kuma a 22 ° C na kwanaki 8 na ƙarshe, yayin da berayen a wasu yanayin zafi ana kiyaye su a wannan zafin na kwanaki 33./33 kwana.An ciyar da beraye a lokacin nazarin.
Nauyi na yau da kullun da berayen DIO sun bi hanyoyin binciken iri ɗaya.A rana -9, an auna mice, an duba MRI, kuma an raba su zuwa kungiyoyi masu kama da nauyin jiki da kuma tsarin jiki.A ranar -7, an canza mice zuwa tsarin rufaffiyar zafin jiki mai sarrafa calorimetry na kai tsaye wanda SABLE Systems International (Nevada, Amurka) ke ƙera.An ajiye beraye daban-daban tare da kayan kwanciya amma ba tare da tsummoki ko kayan matsuguni ba.An saita zafin jiki zuwa 22, 25, 27.5 ko 30 ° C.Bayan mako guda na ƙaddamarwa (kwanaki -7 zuwa 0, dabbobi ba su damu ba), an tattara bayanai a cikin kwanaki hudu a jere (kwanakin 0-4, bayanan da aka nuna a FIGS. 1, 2, 5).Bayan haka, an ajiye beraye a 25, 27.5 da 30 ° C a ƙarƙashin yanayi akai-akai har zuwa ranar 17th.A lokaci guda, ana ƙara yawan zafin jiki a cikin ƙungiyar 22 ° C a tsaka-tsakin 2 ° C kowace rana ta hanyar daidaita yanayin yanayin zafi (06: 00 h) a farkon bayyanar haske (an nuna bayanai a cikin siffa 1). .A rana ta 15, zafin jiki ya ragu zuwa 22 ° C kuma an tattara kwanaki biyu na bayanai don samar da bayanan asali don jiyya na gaba.An ƙara fata zuwa duk mice a ranar 17, kuma an ƙara kayan gida a ranar 20 (Fig. 5).A ranar 23rd, an auna berayen kuma an yi gwajin MRI, sannan a bar su kadai don 24 hours.A ranar 24, beraye sun yi azumi daga farkon lokacin daukar hoto (06:00) kuma sun karɓi OGTT (2 g / kg) a 12:00 (6-7 hours na azumi).Bayan haka, an mayar da berayen zuwa yanayin SABLE daban-daban kuma an kashe su a rana ta biyu (rana 25).
Mice DIO (n = 8) sun bi ka'ida iri ɗaya kamar na beraye masu nauyi na yau da kullun (kamar yadda aka kwatanta a sama da a cikin Hoto 8).Beraye sun kiyaye 45% HFD a duk tsawon gwajin kashe kuzari.
VO2 da VCO2, kazalika da matsa lamba na ruwa, an yi rikodin su a mitar 1 Hz tare da tsawon lokacin tantanin halitta na 2.5 min.An tattara abincin abinci da ruwa ta hanyar ci gaba da yin rikodi (1 Hz) na nauyin kayan abinci da na ruwa.Mai kula da ingancin da aka yi amfani da shi ya ba da rahoton ƙudurin 0.002 g.An yi rikodin matakan ayyuka ta amfani da 3D XYZ beam array Monitor, an tattara bayanai a ƙudurin ciki na 240 Hz kuma an ba da rahoton kowane daƙiƙa don ƙididdige jimlar tazarar tafiya (m) tare da ingantaccen ƙudurin sararin samaniya na 0.25 cm.An sarrafa bayanan tare da Sable Systems Macro Interpreter v.2.41, ƙididdige EE da RER da kuma tace abubuwan waje (misali, abubuwan cin abinci na ƙarya).An saita mai fassarar macro don fitar da bayanai don duk sigogi kowane minti biyar.
Baya ga daidaita EE, yanayin zafin jiki na iya daidaita wasu al'amurran da suka shafi metabolism, ciki har da glucose metabolism na postprandial, ta hanyar daidaita fitar da glucose-metabolizing hormones.Don gwada wannan hasashe, a ƙarshe mun kammala nazarin zafin jiki ta hanyar tsokanar beraye masu nauyi na yau da kullun tare da nauyin glucose na baka (2 g/kg).An bayyana hanyoyin dalla-dalla a cikin ƙarin kayan.
A ƙarshen binciken (rana 25), an yi azumin beraye na sa'o'i 2-3 (farawa daga 06:00), an satar da isoflurane, kuma gaba ɗaya sun zubar da jini ta hanyar retrobital venipuncture.Ƙididdigar adadin lipids na plasma da hormones da lipids a cikin hanta an kwatanta su a cikin Ƙarin Materials.
Don bincika ko yawan zafin jiki na harsashi yana haifar da canje-canje na zahiri a cikin adipose nama wanda ke shafar lipolysis, inguinal da epididymal adipose tissue an cire kai tsaye daga beraye bayan matakin na ƙarshe na zubar jini.An sarrafa nama ta hanyar amfani da sabuwar ƙima ta ex vivo lipolysis da aka bayyana a cikin Ƙarin Hanyoyi.
Brown adipose tissue (BAT) an tattara shi a ranar ƙarshen binciken kuma an sarrafa shi kamar yadda aka bayyana a cikin ƙarin hanyoyin.
Ana gabatar da bayanai azaman ma'ana ± SEM.An ƙirƙiri zane-zane a cikin GraphPad Prism 9 (La Jolla, CA) kuma an tsara zane-zane a cikin Adobe Illustrator (Adobe Systems Incorporated, San Jose, CA).An ƙididdige mahimmancin ƙididdiga a GraphPad Prism kuma an gwada ta ta hanyar t-test, maimaita matakan ANOVA ta hanya ɗaya/hanyoyi biyu da gwajin kwatancen Tukey da yawa, ko ANOVA da ba a haɗa guda ɗaya ba sannan kuma gwajin kwatancen Tukey da yawa kamar yadda ake buƙata.An tabbatar da rarraba Gaussian na bayanan ta hanyar gwajin al'ada na D'Agostino-Pearson kafin gwaji.Ana nuna girman samfurin a cikin sashin da ya dace na sashin "Sakamako", da kuma a cikin almara.Ana bayyana maimaitawa azaman kowane ma'auni da aka ɗauka akan dabba ɗaya (a cikin vivo ko akan samfurin nama).Dangane da sake fasalin bayanai, an nuna haɗin kai tsakanin kashe kuzarin makamashi da yanayin yanayin yanayi a cikin bincike masu zaman kansu guda huɗu ta amfani da ɓeraye daban-daban tare da ƙirar binciken iri ɗaya.
Ana samun cikakkun ƙa'idodin gwaji, kayan aiki, da ɗanyen bayanai bisa buƙata mai ma'ana daga marubucin jagora Rune E. Kuhre.Wannan binciken bai haifar da sabbin reagents na musamman ba, layukan dabba/kwayoyin halitta, ko bayanan jeri.
Don ƙarin bayani game da ƙira na nazari, duba Ƙididdigar Rahoton Bincike mai alaƙa da wannan labarin.
Duk bayanan suna yin jadawali.1-7 an ajiye su a cikin ma'ajin bayanai na Kimiyya, lambar shiga: 1253.11.sciencedb.02284 ko https://doi.org/10.57760/sciencedb.02284.Ana iya aika bayanan da aka nuna a cikin ESM zuwa Rune E Kuhre bayan gwaji mai ma'ana.
Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Dabbobin dakunan gwaje-gwaje a matsayin samfuran maye gurbin kiba na ɗan adam. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Dabbobin dakunan gwaje-gwaje a matsayin samfuran maye gurbin kiba na ɗan adam.Nilsson K, Raun K, Yang FF, Larsen MO.da Tang-Christensen M. Dabbobin dakunan gwaje-gwaje a matsayin samfuran maye gurbin kiba na ɗan adam. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. 实验动物作为人类肥胖的替代模型。 Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Dabbobin gwaji a matsayin abin koyi ga mutane.Nilsson K, Raun K, Yang FF, Larsen MO.da Tang-Christensen M. Dabbobin dakin gwaje-gwaje a matsayin abin maye gurbin kiba a cikin mutane.Acta Pharmacology.laifi 33, 173-181 (2012).
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Fischer, AW, Cannon, B. & Nedergaard, J. Mafi kyawun yanayin mahalli don mice don kwaikwayi yanayin yanayin zafi na mutane: Nazarin gwaji. Fischer, AW, Cannon, B. & Nedergaard, J. Mafi kyawun yanayin mahalli don mice don kwaikwayi yanayin yanayin zafi na mutane: Nazarin gwaji.Fischer, AW, Cannon, B., da Nedergaard, J. Mafi kyawun yanayin yanayin gida don mice don kwaikwayon yanayin yanayin zafi na ɗan adam: Nazarin gwaji. Fischer, AW, Cannon, B. & Nedergaard, J. 小鼠模拟人类热环境的最佳住房温度:一项实验研究。 Fischer, AW, Cannon, B. & Nedergaard, J.Fisher AW, Cannon B., da Nedergaard J. Mafi kyawun zazzabi na mahalli don mice da ke kwaikwayon yanayin yanayin zafi na ɗan adam: Nazarin gwaji.Mooremetabolism.7, 161-170 (2018).
Keijer, J., Li, M. & Speakman, JR Menene mafi kyawun zafin gida don fassara gwaje-gwajen linzamin kwamfuta ga mutane? Keijer, J., Li, M. & Speakman, JR Menene mafi kyawun zafin gida don fassara gwaje-gwajen linzamin kwamfuta ga mutane?Keyer J, Lee M da Speakman JR Menene mafi kyawun zafin jiki don canja wurin gwajin linzamin kwamfuta zuwa mutane? Keijer, J., Li, M. & Speakman, JR 将小鼠实验转化为人类的最佳外壳温度是多少? Keijer, J., Li, M. & Speakman, JRKeyer J, Lee M da Speakman JR Menene mafi kyawun yanayin harsashi don canja wurin gwajin linzamin kwamfuta zuwa ga mutane?Mooremetabolism.25, 168-176 (2019).
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Fischer, AW, Cannon, B. & Nedergaard, J. Amsar tambayar "Mene ne mafi kyawun yanayin gidaje don fassara gwajin linzamin kwamfuta ga mutane?" Fischer, AW, Cannon, B. & Nedergaard, J. Amsar tambayar "Mene ne mafi kyawun yanayin gidaje don fassara gwajin linzamin kwamfuta ga mutane?" Fischer, AW, Cannon, B. & Nedergaard, J. Amsar tambayar "Mene ne mafi kyawun zafin jiki don canja wurin gwaje-gwajen linzamin kwamfuta ga mutane?" Fischer, AW, Cannon, B. & Nedergaard, J. 问题的答案“将小鼠实验转化为人类的最佳外壳温度是多少?” Fischer, AW, Cannon, B. & Nedergaard, J.Fisher AW, Cannon B., da Nedergaard J. Amsoshi ga tambayar "Mene ne mafi kyawun zafin jiki don canja wurin gwaje-gwajen linzamin kwamfuta ga mutane?"Ee: thermoneutral.Mooremetabolism.26, 1-3 (2019).
Lokacin aikawa: Oktoba-28-2022