Hōʻike ka mahana o ke kino i ka hoʻohana ʻana i ka ikehu e uku i ka hoʻolilo ʻana i ka ikehu ma ke kaumaha maʻamau, akā ʻaʻole i hoʻokomo ʻia i ka ʻai, nā ʻiole kāne.

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ʻO ka hapa nui o nā haʻawina metabolic i nā ʻiole e hana ʻia ma ka lumi wela, ʻoiai ma lalo o kēia mau kūlana, ʻaʻole like me nā kānaka, hoʻolilo nā ʻiole i ka nui o ka ikehu e mālama ana i ka mahana o loko.Maʻaneʻi, wehewehe mākou i ke kaumaha maʻamau a me ka meaʻai-induced obesity (DIO) ma C57BL / 6J nāʻiole i hānaiʻia i ka chow chow a iʻole ka 45% kiʻekiʻe o ka momona momona, kēlā me kēia.Hoʻonohoʻia nāʻiole no nā lā 33 ma 22, 25, 27.5 a me 30 ° C. i loko o kahi pūnaewele calorimetry indirect.Hōʻike mākou i ka piʻi ʻana o ka ikehu ma ka laina laina mai 30°C a 22°C a ma kahi o 30% kiʻekiʻe ma 22°C ma nā hiʻohiʻona ʻiole ʻelua.I nā ʻiole kaumaha maʻamau, kūʻē ka ʻai i ka EE.ʻAʻole naʻe i emi iho ka ʻai ʻana o ka ʻiole DIO i ka emi ʻana o ka EE.No laila, i ka pau ʻana o ke aʻo ʻana, ʻoi aku ka kiʻekiʻe o nā ʻiole ma 30 ° C i ke kaumaha o ke kino, ka momona momona a me ka glycerol plasma a me nā triglycerides ma mua o nā ʻiole ma 22 ° C.ʻO ke kaulike ʻole o nā ʻiole DIO ma muli paha o ka hoʻonui ʻana i ka meaʻai e pili ana i ka leʻaleʻa.
ʻO ka ʻiole ka mea hoʻohālike holoholona maʻamau no ke aʻo ʻana i ka physiology kanaka a me ka pathophysiology, a ʻo ia ka holoholona maʻamau i hoʻohana ʻia i ka wā mua o ka ʻike ʻana a me ka hoʻomohala ʻana i ka lāʻau.Eia nō naʻe, ʻokoʻa ka ʻiole mai ke kanaka ma nā ʻano physiological koʻikoʻi, a ʻoiai hiki ke hoʻohana ʻia ka allometric scaling i kekahi ʻano e unuhi i ke kanaka, aia ka ʻokoʻa nui ma waena o nā ʻiole a me nā kānaka i ka thermoregulation a me ka homeostasis ikehu.Hōʻike kēia i kahi kūlike ʻole.ʻO ka awelika o ke kino o nā ʻiole makua he hoʻokahi tausani manawa ka liʻiliʻi ma mua o ko ka poʻe mākua (50 g vs. 50 kg), a ʻokoʻa ka ʻili o ka ʻili i ka ratio nui ma kahi o 400 mau manawa ma muli o ka hoʻololi geometric non-linear i wehewehe ʻia e Mee .Ka hoohalike 2. No ka hopena, ua oi aku ka wela o ka iole e pili ana i ko lakou leo, no laila, ua oi aku ko lakou maalea i ka wela, i oi aku i ka hypothermia, a me ka awelika basal metabolic rate he umi manawa oi aku mamua o ko ke kanaka.Ma ka lumi wela maʻamau (~ 22°C), pono e hoʻonui nā ʻiole i ka nui o ka ikehu (EE) ma kahi o 30% no ka mālama ʻana i ka wela o ke kino.Ma nā mahana haʻahaʻa, piʻi aʻe ka EE ma kahi o 50% a me 100% ma 15 a me 7°C i hoʻohālikelike ʻia me EE ma 22°C.No laila, ʻo nā kūlana hale maʻamau e hoʻoulu ai i kahi pane koʻikoʻi anu, hiki ke hoʻololi i ka hoʻololi ʻana o nā hopena ʻiole i nā kānaka, ʻoiai ʻo nā kānaka e noho nei i nā hui hou e hoʻolilo i ka hapa nui o ko lākou manawa i nā kūlana thermoneutral (no ka mea, ʻo kā mākou ʻāpana haʻahaʻa i ka leo e emi ai ko mākou naʻau. ʻO ka mahana, ʻoiai mākou e hana i kahi thermoneutral zone (TNZ) a puni mākou ma luna o ka basal metabolic rate) ma kahi ~ 19 a 30 ° C6, ʻoiai ʻo nā ʻiole he kiʻekiʻe a ʻoi aku ka liʻiliʻi o ka 2-4 ° C7,8 ʻO ka mea nui. Ua loaʻa ka manaʻo nui i nā makahiki i hala iho nei 4, 7,8,9,10,11,12 a ua manaʻo ʻia e hiki ke hoʻemi ʻia kekahi mau "ʻokoʻa ʻano" ma o ka hoʻonui ʻana i ka mahana o ka pūpū 9. Akā naʻe, ʻaʻohe manaʻo i ka pae wela. ʻo ia ka thermoneutrality i nā ʻiole.No laila, ʻoi aku ka pili o ka mahana koʻikoʻi haʻahaʻa o ka thermoneutral i nā ʻiole kuli hoʻokahi i ka 25°C a i ʻole kokoke i 30°C4, 7, 8, 10, 12 mau mea hoʻopaʻapaʻa.ʻO ka EE a me nā ʻāpana metabolic ʻē aʻe i kaupalena ʻia i nā hola a i nā lā, no laila ʻaʻole maopopo ka nui o ka lōʻihi o ka ʻike ʻana i nā wela like ʻole e pili ana i nā ʻāpana metabolic e like me ke kaumaha o ke kino.ka hoʻohana ʻana, ka hoʻohana ʻana i ka substrate, ka ʻae ʻana i ka glucose, a me ka lipid plasma a me ka glucose concentrations a me nā hormones hoʻoponopono makemake.Eia hou, pono ka noiʻi hou ʻana e ʻike i ka nui o ka hopena o ka meaʻai i kēia mau ʻāpana (ʻoi aku ka huli ʻana o nā ʻiole DIO i ka meaʻai momona kiʻekiʻe i ka meaʻai ʻoliʻoli (hedonic).No ka hāʻawi ʻana i ka ʻike hou aʻe e pili ana i kēia kumuhana, ua nānā mākou i ka hopena o ka hānai ʻana i ka mahana ma nā ʻāpana metabolic i ʻōlelo ʻia ma mua o nā ʻiole kāne makua maʻamau a me nā ʻiole kāne momona momona (DIO) i ka 45% momona momona.Ua mālama ʻia nā ʻiole ma 22, 25, 27.5, a i ʻole 30 ° C no ʻekolu pule.ʻAʻole i aʻo ʻia nā mahana ma lalo o 22°C no ka mea ʻaʻole i aʻo ʻia nā hale holoholona maʻamau ma lalo o ka mahana wela.Ua ʻike mākou ua pane like nā ʻiole DIO paona maʻamau a me ka pōʻai hoʻokahi i nā loli i ka mahana o ka pā e pili ana i ka EE a me ka nānā ʻole ʻana i ke ʻano o ka pā (me ka ʻole a i ʻole nā ​​​​mea hoʻomalu.Eia naʻe, ʻoiai ua hoʻoponopono nā ʻiole kaumaha maʻamau i kā lākou ʻai ʻana e like me ka EE, ʻo ka ʻai ʻana o nā ʻiole DIO i kūʻokoʻa nui ʻia i ka EE, ka hopena i ka piʻi ʻana o ke kaumaha o nā ʻiole.Wahi a ka ʻikepili kaumaha o ke kino, ua hōʻike ʻia ka ʻike plasma o nā lipids a me nā kino ketone he ʻoi aku ka maikaʻi o ka ʻiole DIO ma 30 ° C ma mua o nā ʻiole ma 22 ° C.ʻO nā kumu kumu o nā ʻokoʻa i ke kaulike o ka lawe ʻana i ka ikehu a me ka EE ma waena o ke kaumaha maʻamau a me nā ʻiole DIO e pono e aʻo hou aku, akā pili paha i nā loli pathophysiological i nā ʻiole DIO a me ka hopena o ka ʻai ʻana i ka leʻaleʻa ma muli o ka ʻai momona.
Ua hoʻonui ʻia ʻo EE i ka laina laina mai 30 a 22 ° C a ma kahi o 30% kiʻekiʻe ma 22 ° C i hoʻohālikelike ʻia me 30 ° C (Fig. 1a, b).ʻO ka hoʻololi o ka hanu (RER) kūʻokoʻa i ka mahana (Fig. 1c, d).Ua kūlike ka meaʻai me ka dynamics EE a ua hoʻonui ʻia me ka emi ʻana o ka mahana (ʻo ia hoʻi ~ 30% kiʻekiʻe ma 22 ° C i hoʻohālikelike ʻia me 30 ° C (Fig. 1e, f). ʻO ka lawe wai. ʻAʻole i hilinaʻi ka nui a me ka pae hana i ka mahana (Fig. 1g ).
ʻO nāʻiole kāne (C57BL / 6J, 20 mau wiki, hale hoʻokahi, n = 7) i hoʻopaʻaʻia i loko o nā hīnaʻi metabolic ma 22 ° C. no hoʻokahi pule ma mua o ka hoʻomakaʻana o ke aʻoʻana.ʻElua mau lā ma hope o ka hōʻiliʻili ʻana o ka ʻikepili hope, ua hoʻonui ʻia ka mahana ma 2 ° C increments ma 06:00 hola i kēlā me kēia lā (hoʻomaka ʻana o ka māhele māmā).Hōʻike ʻia ka ʻikepili ma ke ʻano he mean ± hapa maʻamau o ka mean, a hōʻike ʻia ka manawa pōʻeleʻele (18:00–06:00 h) e kahi pahu hina.a Ka lilo ikehu (kcal/h), b Ka huina o ka lilo ikehu ma na wela like ole (kcal/24 h), c Ka huina hoonui hanu (VCO2/VO2: 0.7–1.0), d Mean RER ma ka malamalama a me ka pouli (VCO2 /VO2) mahele (wehe ʻia ka waiwai ʻeleʻele he 0.7).e hui 'ai mea'ai (g), f 24h huina mea'ai, g 24h huina wai (ml), h 24h huina wai, i kumulative pae hana (m) a j huina hana pae (m/24h) .).Mālama ʻia nā ʻiole ma kahi mahana i hōʻike ʻia no 48 mau hola.Hōʻike ka ʻikepili i hōʻike ʻia no 24, 26, 28 a me 30°C i nā hola 24 hope loa o kēlā me kēia pōʻai.Ua hānai ʻia nā ʻiole i ke aʻo ʻana.Ua hoʻāʻo ʻia ke koʻikoʻi helu helu e nā ana pinepine ʻana o ka ANOVA ala hoʻokahi a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey.Hōʻike nā Asterisk i ke koʻikoʻi no ka waiwai mua o 22 ° C, hōʻike ka shading i ke koʻikoʻi ma waena o nā hui ʻē aʻe e like me ka mea i hōʻike ʻia. *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.Ua helu ʻia nā waiwai maʻamau no ka manawa hoʻokolohua holoʻokoʻa (0-192 mau hola).n = 7.
E like me ke ʻano o nā ʻiole kaumaha maʻamau, hoʻonui ʻia ka EE me ka hoʻohaʻahaʻa ʻana i ka mahana, a ma kēia hihia, ʻoi aku ka nui o EE ma kahi o 30% kiʻekiʻe ma 22 ° C i hoʻohālikelike ʻia me 30 ° C (Fig. 2a,b).ʻAʻole i loli ka RER i nā mahana like ʻole (Fig. 2c, d).ʻOkoʻa me nā ʻiole kaumaha maʻamau, ʻaʻole i kūlike ka ʻai ʻana me ka EE ma ke ʻano he hana o ka wela lumi.ʻO ka ʻai ʻana i ka meaʻai, ka ʻai ʻana i ka wai, a me ka pae hana he kūʻokoʻa i ka mahana (Fig. 2e-j).
Kāne (C57BL / 6J, 20 wiki) Ua hoʻopaʻa ʻia nā ʻiole DIO i loko o nā hīnaʻi metabolic ma 22 ° C. no hoʻokahi pule ma mua o ka hoʻomaka ʻana o ke aʻo ʻana.Hiki i nā ʻiole ke hoʻohana i ka 45% HFD ad libitum.Ma hope o ka acclimatization no nā lā ʻelua, ua hōʻiliʻili ʻia ka ʻikepili baseline.Ma hope mai, ua hoʻonui ʻia ka mahana ma kahi o 2°C i kēlā me kēia lā ma 06:00 (hoʻomaka ʻana o ka māhele māmā).Hōʻike ʻia ka ʻikepili ma ke ʻano he mean ± hapa maʻamau o ka mean, a hōʻike ʻia ka manawa pōʻeleʻele (18:00–06:00 h) e kahi pahu hina.a Ka lilo ikehu (kcal/h), b Ka huina o ka lilo ikehu ma na wela like ole (kcal/24 h), c Ka huina hoonui hanu (VCO2/VO2: 0.7–1.0), d Mean RER ma ka malamalama a me ka pouli (VCO2 /VO2) mahele (wehe ʻia ka waiwai ʻeleʻele he 0.7).e hui 'ai mea'ai (g), f 24h huina mea'ai, g 24h huina wai (ml), h 24h huina wai, i kumulative pae hana (m) a j huina hana pae (m/24h) .).Mālama ʻia nā ʻiole ma kahi mahana i hōʻike ʻia no 48 mau hola.Hōʻike ka ʻikepili i hōʻike ʻia no 24, 26, 28 a me 30°C i nā hola 24 hope loa o kēlā me kēia pōʻai.Ua mālama ʻia nā ʻiole ma 45% HFD a hiki i ka pau ʻana o ke aʻo ʻana.Ua hoʻāʻo ʻia ke koʻikoʻi helu helu e nā ana pinepine ʻana o ka ANOVA ala hoʻokahi a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey.Hōʻike nā Asterisk i ke koʻikoʻi no ka waiwai mua o 22 ° C, hōʻike ka shading i ke koʻikoʻi ma waena o nā hui ʻē aʻe e like me ka mea i hōʻike ʻia. *P < 0.05, ***P < 0.001, ****P < 0.0001. *P < 0.05, ***P < 0.001, ****P < 0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001. *P <0.05，***P <0.001，****P <0.0001. *P <0.05，***P <0.001，****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Ua helu ʻia nā waiwai maʻamau no ka manawa hoʻokolohua holoʻokoʻa (0-192 mau hola).n = 7.
Ma nā ʻano hoʻokolohua ʻē aʻe, ua nānā mākou i ka hopena o ka wela ambient ma nā ʻāpana like, akā i kēia manawa ma waena o nā pūʻulu ʻiole i mālama mau ʻia i kahi mahana.Ua māhele ʻia nā ʻiole i ʻehā mau pūʻulu e hōʻemi i ka hoʻololi ʻana i ka helu helu i ka mean a me ke ʻano maʻamau o ke kaumaha o ke kino, ka momona, a me ke kaumaha o ke kino maʻamau (Fig. 3a-c).Ma hope o 7 lā o ka acclimatization, 4.5 lā o EE i hoʻopaʻa ʻia.Hoʻopilikia nui ʻia ka EE e ka wela o ke ao ma nā hola o ke ao a me ka pō (Fig. 3d), a piʻi i ka laina laina i ka emi ʻana o ka mahana mai 27.5 ° C a i 22 ° C (Fig. 3e).Ke hoʻohālikelikeʻia me nā hui'ē aʻe, ua emi iki ka RER o ka hui 25 ° C, aʻaʻohe mea likeʻole ma waena o nā hui i koe (Fig. 3f, g).Ua hoʻonui ʻia ka ʻai meaʻai me ke kumu EE ma kahi o 30% ma 22°C i hoʻohālikelike ʻia me 30°C (Fig. 3h,i).ʻAʻole i ʻokoʻa loa ka hoʻohana ʻana i ka wai a me nā pae hana ma waena o nā hui (Fig. 3j, k).ʻO ka ʻike ʻana i nā mahana like ʻole a hiki i nā lā 33 ʻaʻole ia i alakaʻi i nā ʻokoʻa o ke kaumaha o ke kino, ka lean mass, a me ka momona momona ma waena o nā hui (Fig. 3n-s), akā ua hopena i ka emi ʻana o ka nui o ke kino lean ma kahi o 15% i hoʻohālikelike ʻia me nā helu hōʻike pilikino (Fig. 3n-s).3b, r, c)) a ua hoʻonui ʻia ka momona momona ma mua o 2 mau manawa (mai ~ 1 g i 2-3 g, Fig. 3c, t, c).ʻO ka mea pōʻino, loaʻa i ka cabinet 30 ° C nā hewa calibration a ʻaʻole hiki ke hāʻawi i ka ʻikepili EE a me RER pololei.
- Ke kaumaha o ke kino (a), ka lean mass (b) a me ka momona (c) ma hope o 8 mau lā (hoʻokahi lā ma mua o ka hoʻololi ʻana i ka ʻōnaehana SABLE).d Hoʻohana ikehu (kcal/h).e Awelika hoʻohana ikehu (0–108 hola) ma nā wela like ʻole (kcal/24 hola).f Lakiō hoʻololi hanu (RER) (VCO2/VO2).g Mean RER (VCO2/VO2).h Ka huina meaʻai (g).i ʻO ka ʻai ʻana o ka meaʻai (g/24 hola).j Ka huina wai hoohana (ml).k Awelika hoʻohana wai (ml/24 h).l Kūlana haʻawina hui (m).m Ka pae hana maʻamau (m/24 h).n ke kaumaha o ke kino ma ka la 18, o ka hoololi ana i ke kaumaha o ke kino (mai ka -8 a hiki i ka la 18), p ka lean ma ka 18 o ka la, q hoololi i ka lean mass (mai ka -8 a hiki i ka 18 o ka la ), r ka momona o ka la 18 , a hoʻololi i ka momona momona (mai -8 a 18 lā).Ua ho'āʻo ʻia ke koʻikoʻi helu helu o nā ana hou ʻia e Oneway-ANOVA a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. *P <0,05, **P <0,01, ***P <0,001, ****P <0,0001. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. *P <0.05，**P <0.01，***P <0.001，****P <0.0001. *P <0.05，**P <0.01，***P <0.001，****P <0.0001. *P <0,05, **P <0,01, ***P <0,001, ****P <0,0001. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.Hōʻike ʻia ka ʻikepili ma ke ʻano he mean + hapa maʻamau o ka mean, ʻo ka pōʻeleʻele (18:00-06:00 h) hōʻike ʻia e nā pahu hina.Hōʻike nā kiko ma nā histograms i nā ʻiole pākahi.Ua helu ʻia nā helu maʻamau no ka manawa hoʻokolohua holoʻokoʻa (0-108 mau hola).n = 7.
Ua hoʻohālikelikeʻia nāʻiole i ke kaumaha o ke kino, ka lean mass, a me ka momona momona ma ke kumu (Figs. 4a-c) a mālamaʻia ma 22, 25, 27.5, a me 30 ° C e like me nā haʻawina me nāʻiole kaumaha maʻamau..I ka hoʻohālikelike ʻana i nā pūʻulu ʻiole, ua hōʻike ka pilina ma waena o EE a me ka mahana i kahi pilina laina like me ka mahana ma luna o ka manawa ma nā ʻiole like.No laila,ʻo nāʻiole i mālamaʻia ma 22 ° C e hoʻopau i ka 30% o ka ikehu ma mua o nāʻiole i mālamaʻia ma 30 ° C (Fig. 4d, e).I ke aʻo ʻana i nā hopena i loko o nā holoholona, ​​ʻaʻole i pili ka mahana i ka RER (Fig. 4f,g).ʻAʻole i hoʻopilikia nui ʻia ka ʻai, ka wai, a me ka hana e ka wela (Fig. 4h–m).Ma hope o 33 mau lā o ka hānaiʻana, uaʻoi aku ka nui o ke kaumaha o ke kino i nāʻiole ma 30 ° C ma mua o nāʻiole ma 22 ° C (Fig. 4n).Ke hoʻohālikelikeʻia i ko lākou mau kumu kiko'ī,ʻo nāʻiole i hānaiʻia ma 30 ° C uaʻoi aku ka nui o ke kaumaha o ke kino ma mua o nāʻiole i hānaiʻia ma 22 ° C (mean ± standard error of the mean: Fig. 4o).ʻO ka piʻiʻana o ke kaumaha ma muli o ka piʻiʻana o ka momona momona (Fig. 4p, q) ma mua o ka piʻiʻana o ka lean mass (Fig. 4r, s).E like me ka helu EE haʻahaʻa ma 30 ° C, ua ho'ēmiʻia ka'ōlelo o kekahi mau genes BAT e hoʻonui ana i ka hana / hana BAT ma 30 ° C i hoʻohālikelikeʻia me 22 ° C: Adra1a, Adrb3, a me Prdm16.ʻAʻole i hoʻopilikia ʻia nā ʻano kī nui ʻē aʻe e hoʻonui ai i ka hana / hana BAT: Sema3a (neurite growth regulation), Tfam (mitochondrial biogenesis), Adrb1, Adra2a, Pck1 (gluconeogenesis) a me Cpt1a.ʻO ka mea kupanaha, ʻo Ucp1 a me Vegf-a, pili me ka hoʻonui ʻana i ka hana thermogenic, ʻaʻole i emi i ka hui 30 ° C.ʻO kaʻoiaʻiʻo, uaʻoi aku ka kiʻekiʻe o ka Ucp1 i nāʻioleʻekolu ma mua o ka hui 22 ° C, a ua hoʻokiʻekiʻe nuiʻiaʻo Vegf-a a me Adrb2.Hoʻohālikelike ʻia me ka hui 22 ° C, mālama ʻia nā ʻiole ma 25 ° C a me 27.5 ° C i hōʻike ʻole i kahi loli (Supplementary Figure 1).
- Ke kaumaha o ke kino (a), ka lean mass (b) a me ka momona (c) ma hope o 9 mau lā (hoʻokahi lā ma mua o ka hoʻololi ʻana i ka ʻōnaehana SABLE).d Hoʻohana ikehu (EE, kcal/h).e Awelika hoʻohana ikehu (0–96 hola) ma nā mahana like ʻole (kcal/24 hola).f Lakiō hoʻololi hanu (RER, VCO2/VO2).g Mean RER (VCO2/VO2).h Ka huina meaʻai (g).i ʻO ka ʻai ʻana o ka meaʻai (g/24 hola).j Ka huina wai hoohana (ml).k Awelika hoʻohana wai (ml/24 h).l Kūlana haʻawina hui (m).m Ka pae hana maʻamau (m/24 h).n Ke kaumaha o ke kino i ka lā 23 (g), o Hoʻololi i ke kaumaha o ke kino, p Lean mass, q Hoʻololi i ka lean mass (g) i ka lā 23 i hoʻohālikelike ʻia me ka lā 9, Hoʻololi i ka nui momona (g) i ​23 -lā, momona nuipa (g) i hoʻohālikelike ʻia i ka lā 8, lā 23 i hoʻohālikelike ʻia me ka lā -8th.Ua ho'āʻo ʻia ke koʻikoʻi helu helu o nā ana hou ʻia e Oneway-ANOVA a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey. *P < 0.05, ***P < 0.001, ****P < 0.0001. *P < 0.05, ***P < 0.001, ****P < 0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001. *P <0.05，***P <0.001，****P <0.0001. *P <0.05，***P <0.001，****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Hōʻike ʻia ka ʻikepili ma ke ʻano he mean + hapa maʻamau o ka mean, ʻo ka pōʻeleʻele (18:00-06:00 h) hōʻike ʻia e nā pahu hina.Hōʻike nā kiko ma nā histograms i nā ʻiole pākahi.Ua helu ʻia nā helu mean no ka manawa hoʻokolohua holoʻokoʻa (0-96 mau hola).n = 7.
E like me nā kānaka, hana pinepine nā ʻiole i nā microenvironments e hōʻemi i ka nalowale o ka wela i ke kaiapuni.No ka helu ʻana i ke koʻikoʻi o kēia kaiapuni no EE, ua loiloi mākou iā EE ma 22, 25, 27.5, a me 30°C, me nā kiaʻi ʻili a me nā mea hoʻopunahele.Ma 22 ° C, ka hoʻohui ʻana o nā ʻili maʻamau e hōʻemi i ka EE ma kahi o 4%.ʻO ka hoʻohui hou ʻana o nā mea nesting i hoʻemi i ka EE e 3-4% (Fig. 5a, b).ʻAʻohe hoʻololi koʻikoʻi i ka RER, ka ʻai ʻana i ka meaʻai, ka lawe ʻana i ka wai, a i ʻole nā ​​pae hana i ʻike ʻia me ka hoʻohui ʻana o nā hale a i ʻole nā ​​​​ʻili + moe (Figure 5i–p).ʻO ka hoʻohui ʻana i ka ʻili a me nā mea pūnana i hoʻemi nui i ka EE ma 25 a me 30 ° C, akā ʻoi aku ka liʻiliʻi o nā pane.Ma 27.5 ° C ʻaʻohe ʻokoʻa i ʻike ʻia.ʻO ka mea nui, ma kēia mau hoʻokolohua, emi iho ka EE me ka piʻi ʻana o ka mahana, ma kēia hihia ma kahi o 57% haʻahaʻa ma mua o EE ma 30 ° C i hoʻohālikelike ʻia me 22 ° C (Fig. 5c–h).Hana ʻia ka loiloi like ʻana no ka manawa māmā, kahi i kokoke ai ka EE i ka pae basal metabolic rate, no ka mea, ma kēia ʻano, hoʻomaha ka nui o nā ʻiole i ka ʻili, e like me ka nui o ka hopena ma nā mahana like ʻole (Supplementary Fig. 2a–h). .
ʻikepili no nā ʻiole mai ka hale a me nā mea pūnana (uliuli ʻeleʻele), home akā ʻaʻohe mea nesting (uliuli māmā), a me nā mea home a me ka pūnana (alani).ʻO ka hoʻohana ʻana i ka ikehu (EE, kcal/h) no nā lumi a, c, e a me g ma 22, 25, 27.5 a me 30 °C, b, d, f a me h ʻo ia hoʻi ʻo EE (kcal/h).ip ʻIkepili no nā ʻiole i waiho ʻia ma 22°C: i ka hanu hanu (RER, VCO2/VO2), j mean RER (VCO2/VO2), k kumulative intake meaʻai (g), l awelika ʻai meaʻai (g/24 h) , m ka nui o ka lawe wai (mL), n ka nui o ka lawe wai AUC (mL/24h), o ka nui o ka hana (m), p awelika pae hana (m/24h).Hōʻike ʻia ka ʻikepili ma ke ʻano he mean + hapa maʻamau o ka mean, ʻo ka pōʻeleʻele (18:00-06:00 h) hōʻike ʻia e nā pahu hina.Hōʻike nā kiko ma nā histograms i nā ʻiole pākahi.Ua ho'āʻo ʻia ke koʻikoʻi helu helu o nā ana hou ʻia e Oneway-ANOVA a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey. *P <0.05, **P <0.01. *P <0.05, **P <0.01. *Р<0,05, **Р<0,01. *P<0.05, **P<0.01. *P <0.05，**P <0.01. *P <0.05，**P <0.01. *Р<0,05, **Р<0,01. *P<0.05, **P<0.01.Ua helu ʻia nā waiwai maʻamau no ka manawa hoʻokolohua holoʻokoʻa (0-72 mau hola).n = 7.
I nāʻiole kaumaha maʻamau (2-3 mau hola o ka hoʻokēʻaiʻana),ʻo ka hānaiʻana i nā mahana likeʻole i hopena i nāʻokoʻa nui o ka plasma concentrations o TG, 3-HB, cholesterol, ALT, a me AST, akā HDL ma keʻano he hana o ka mahana.Kii 6a-e).ʻAʻole ʻokoʻa ka nui o ka leptin, insulin, C-peptide, a me glucagon ma waena o nā hui (Nā kiʻi 6g-j).I ka lā o ka hoʻāʻo ʻana i ka glucose tolerance (ma hope o 31 mau lā i nā mahana like ʻole), ʻo ke kiʻekiʻe o ka glucose koko kumu (5-6 mau hola o ka hoʻokē ʻai) ma kahi o 6.5 mM, ʻaʻohe ʻokoʻa ma waena o nā hui. ʻO ka hoʻohana ʻana i ka glucose waha ua hoʻonui nui ʻia ka nui o ka glucose koko ma nā pūʻulu āpau, akā ʻoi aku ka haʻahaʻa o ka pae kiʻekiʻe a me ka wahi i hoʻonui ʻia ma lalo o nā pihi (iAUCs) (15-120 min) i loko o ka hui o nā ʻiole i hoʻopaʻa ʻia ma 30 °C (nā manawa pākahi: P <0.05-P <0.0001, Fig. 6k, l) i hoʻohālikelike ʻia me nā ʻiole i noho ʻia ma 22, 25 a me 27.5 ° C (ʻaʻole i ʻokoʻa kekahi i kekahi). ʻO ka hoʻohana ʻana i ka glucose waha ua hoʻonui nui ʻia ka nui o ka glucose koko ma nā pūʻulu āpau, akā ʻoi aku ka haʻahaʻa o ka pae kiʻekiʻe a me ka wahi i hoʻonui ʻia ma lalo o nā pihi (iAUCs) (15-120 min) i loko o ka hui o nā ʻiole i hoʻopaʻa ʻia ma 30 °C (nā manawa pākahi: P <0.05-P <0.0001, Fig. 6k, l) i hoʻohālikelikeʻia me nāʻiole i nohoʻia ma 22, 25 a me 27.5 ° C (ʻaʻole i likeʻole kekahi i kekahi). Пероральное введение глюкозы значительно повышало концентрацию глюкозы в крови во всех группах, китрацию площадь приращения под кривыми (iAUC) (15–120 мин) были ниже в группе мышей, содержащихся при 30 °C (mai ke kau wela: < 0,05–P < 0,0001, рис. ʻO ka hoʻohana waha ʻana o ka glucose i hoʻonui nui i ka nui o ka glucose i ke koko ma nā hui āpau, akā ʻoi aku ka haʻahaʻa o ka pae kiʻekiʻe a me ka wahi hoʻonui ma lalo o nā pihi (iAUC) (15-120 min) i loko o ka hui ʻiole 30 ° C (nā manawa kaʻawale: P <0.05- P <0.0001, Fig. 6k, l) i hoʻohālikelikeʻia me nāʻiole i mālamaʻia ma 22, 25 a me 27.5 °C (ʻaʻole iʻokoʻa kekahi i kekahi).口服葡萄糖的给药显着增加了所有组的血糖浓度，但在30 °C 饲养的小鼠组中，小鼠组中，峰为個面积(iAUC) (15-120 分钟) 均较低（各个时间点：P < 0.05–P < 0.0001，图6k，l）与饲养在22、25 和27.5°C 的小鼠（彼此之间没有差异）。口服 葡萄糖 的 给 药 显着 了 所有组 的 血糖 浓度 但 在 在 在 30 ° C 饲养 小线 下 增加 面积 面积 (IAUC) (15-120 分钟) 均 较 低 各 个 点 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（彼此之间没有差。ʻO ka hoʻohana waha o ka glucose i hoʻonui nui i ka nui o ka glucose koko ma nā hui āpau, akā ʻoi aku ka haʻahaʻa o ka piko a me ka wahi ma lalo o ka curve (iAUC) (15-120 min) i loko o ka pūʻulu ʻiole 30 ° C-fed (nā manawa āpau).: P < 0,05–P < 0,0001, рис. : P < 0.05–P < 0.0001, Fig.6l, l) i hoʻohālikelike ʻia me nā ʻiole i mālama ʻia ma 22, 25 a me 27.5 ° C (ʻaʻohe ʻokoʻa mai kekahi i kekahi).
Hōʻike ʻia ka nui o ka plasma o TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, a me glucagon i nā ʻiole kāne DIO (al) makua ma hope o 33 mau lā o ka hānai ʻana i ka mahana i hōʻike ʻia. .ʻAʻole hānai ʻia nā ʻiole 2-3 mau hola ma mua o ka hoʻāʻo ʻana i ke koko.ʻO ka mea ʻē aʻe he hoʻāʻo hoʻomanawanui glucose waha, i hana ʻia i ʻelua mau lā ma mua o ka pau ʻana o ke aʻo ʻana i nā ʻiole i hoʻokē ʻai no 5-6 mau hola a mālama ʻia i ka mahana kūpono no 31 mau lā.Hoʻopiʻi ʻia nā ʻiole me 2 g/kg paona kino.Hōʻike ʻia ka ʻāpana ma lalo o ka ʻikepili curve (L) ma ke ʻano he ʻikepili hoʻonui (iAUC).Hōʻike ʻia ka ʻikepili ma ke ʻano he ± SEM.Hōʻike nā kiko i nā laʻana pākahi. *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.
I nāʻiole DIO (hoʻokēʻai hoʻi no nā hola 2-3), ʻaʻole ʻokoʻa nā ʻano ʻokoʻa o ka cholesterol plasma, HDL, ALT, AST, a me FFA ma waena o nā hui.Ua hoʻokiʻekiʻe nui ʻia ka TG a me ka glycerol i ka hui 30 ° C i hoʻohālikelike ʻia me ka hui 22 ° C (Nā kiʻi 7a-h).ʻO ka hoʻohālikelike, 3-GB ma kahi o 25% haʻahaʻa ma 30 ° C i hoʻohālikelike ʻia me 22 ° C (Figure 7b).No laila, ʻoiai ʻo nā ʻiole i mālama ʻia ma 22 ° C he koena ikehu maikaʻi holoʻokoʻa, e like me ka manaʻo o ka loaʻa ʻana o ke kaumaha, ʻokoʻa ka ʻokoʻa o ka plasma concentrations o TG, glycerol, a me 3-HB e hōʻike ana i nā ʻiole ma 22 ° C ke emi iho ka laʻana ma mua o 22 °. C.°C.ʻO nā ʻiole i hānai ʻia ma 30 °C aia i loko o kahi kūlana maikaʻi ʻole.Kūlike me kēia, ʻoi aku ka kiʻekiʻe o ka ate o ka glycerol extractable a me TG, akā ʻaʻole glycogen a me cholesterol, i ka hui 30 ° C (Supplementary Fig. 3a-d).No ka noiʻi ʻana inā ʻo nā ʻokoʻa pili i ka wela o ka lipolysis (e like me ke ana ʻana e ka plasma TG a me ka glycerol) ka hopena o nā hoʻololi i loko o ka epididymal a i ʻole ka momona inguinal, lawe mākou i nā kiko adipose mai kēia mau hale kūʻai i ka pau ʻana o ke aʻo ʻana a helu ʻia ka momona momona ex ex. vivo.a hoʻokuʻu i ka glycerol.I loko o nā pūʻulu hoʻokolohua a pau, ua hōʻike ʻia nā ʻano kiko adipose mai ka epididymal a me ka inguinal depots ma ka liʻiliʻi he ʻelua mau piʻi o ka glycerol a me ka hana FFA ma ka pane ʻana i ka isoproterenol stimulation (Supplementary Fig. 4a-d).Eia naʻe, ʻaʻohe hopena o ka wela o ka pūpū ma ka lipolysis i hoʻoulu ʻia i ka basal a i ʻole isoproterenol.E like me ke kaumaha o ke kino kiʻekiʻe a me ka nui o ka momona, ʻoi aku ka kiʻekiʻe o ka pae leptin plasma i ka hui 30 ° C ma mua o ka hui 22 ° C (Figure 7i).ʻO ka mea ʻē aʻe, ʻaʻole ʻokoʻa nā pae plasma o ka insulin a me ka C-peptide ma waena o nā pūʻulu wela (Fig. 7k, k), akā ua hōʻike ʻia ka glucagon plasma i ka hilinaʻi ʻana i ka mahana, akā i kēia hihia kokoke i 22 ° C i ka hui ʻē aʻe ua hoʻohālikelike ʻia ʻelua. i 30°C.MAI.Hui C (Fig. 7l).ʻAʻole ʻokoʻa ka FGF21 ma waena o nā hui wela like ʻole (Fig. 7m).Ma ka lā o OGTT, he 10 mM ka nui o ka glucose koko kumu a ʻaʻole ʻokoʻa ma waena o nā ʻiole i noho ʻia ma nā mahana like ʻole (Fig. 7n).ʻO ka hoʻokele waha o ka glucose i hoʻonui i ke kiʻekiʻe o ka glucose i ke koko a piʻi i ka piko i nā hui āpau ma kahi o 18 mM 15 mau minuke ma hope o ka lawe ʻana.ʻAʻohe ʻokoʻa koʻikoʻi ma iAUC (15-120 min) a me ka hoʻopaʻa ʻana i nā manawa like ʻole ma hope o ka hopena (15, 30, 60, 90 a me 120 min) (Figure 7n, o).
Ua hōʻike ʻia nā pae plasma o TG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulin, C-peptide, glucagon, a me FGF21 i nā ʻiole kāne makua DIO (ao) ma hope o 33 mau lā o ka hānai ʻana.wela i kuhikuhi ʻia.ʻAʻole hānai ʻia nā ʻiole 2-3 mau hola ma mua o ka hoʻāʻo ʻana i ke koko.He ʻokoʻa ka hoʻāʻo ʻana o ka glucose oral no ka mea i hana ʻia ma kahi ʻano o 2 g / kg paona kino ʻelua mau lā ma mua o ka pau ʻana o ke aʻo ʻana i nā ʻiole i hoʻokē ʻai ʻia no 5-6 mau hola a mālama ʻia i ka mahana kūpono no 31 mau lā.Hōʻike ʻia ka ʻāpana ma lalo o ka ʻikepili pihi (o) ma ke ʻano he ʻikepili hoʻonui (iAUC).Hōʻike ʻia ka ʻikepili ma ke ʻano he ± SEM.Hōʻike nā kiko i nā laʻana pākahi. *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.
ʻO ka hoʻololi ʻana o ka ʻikepili rodent i nā kānaka he pilikia paʻakikī e pāʻani i ke koʻikoʻi i ka wehewehe ʻana i ke koʻikoʻi o ka nānā ʻana i ka pōʻaiapili o ka noiʻi physiological a me pharmacological.No nā kumu waiwai a no ka hoʻomaʻamaʻa ʻana i ka noiʻi, mālama pinepine ʻia nā ʻiole ma ka lumi wela ma lalo o kā lākou thermoneutral zone, ka hopena i ka hoʻōla ʻana o nā ʻōnaehana physiological compensatory e hoʻonui ai i ka helu metabolic a hiki ke hōʻino i ka translatability9.No laila, ʻo ka ʻike ʻana i nā ʻiole i ke anu hiki ke hoʻololi i nā ʻiole i ka momona i hoʻokomo ʻia i ka meaʻai a hiki ke pale i ka hyperglycemia i nā ʻiole i mālama ʻia e streptozotocin ma muli o ka hoʻonui ʻana i ka lawe ʻana i ka glucose i hilinaʻi ʻole i ka insulin.Eia naʻe, ʻaʻole maopopo i ka nui o ka loaʻa ʻana o ka lōʻihi i nā wela kūpono (mai ka lumi a i ka thermoneutral) e pili ana i ka homeostasis ikehu like ʻole o nā ʻiole kaumaha maʻamau (ma ka meaʻai) a me nā ʻiole DIO (ma ka HFD) a me nā ʻāpana metabolic, a me ka laulā. i hiki ai iā lākou ke kaulike i ka piʻi ʻana o ka EE me ka hoʻonui ʻana i ka ʻai.ʻO ka haʻawina i hōʻike ʻia ma kēia ʻatikala ke manaʻo nei e lawe i kahi akaka i kēia kumuhana.
Hōʻike mākou i nā ʻiole makua paona maʻamau a me nā ʻiole DIO kāne, pili like ʻole ʻo EE i ka wela o ka lumi ma waena o 22 a 30°C.No laila, ʻo EE ma 22°C ma kahi o 30% kiʻekiʻe ma mua o 30°C.ma nā ʻano ʻiole ʻelua.Eia naʻe, he ʻokoʻa koʻikoʻi ma waena o nā ʻiole paona maʻamau a me nā ʻiole DIO ʻoiai ʻo nā ʻiole kaumaha maʻamau i kūlike me EE ma nā haʻahaʻa haʻahaʻa ma o ka hoʻoponopono ʻana i ka ʻai ʻana e like me ia, ʻokoʻa ka ʻai ʻana o nā ʻiole DIO ma nā pae like ʻole.Ua like nā mahana haʻawina.Ma hope o hoʻokahi mahina, loaʻa i nā ʻiole DIO i mālama ʻia ma 30 ° C ke kaumaha o ke kino a me ka nui o ka momona ma mua o nā ʻiole i mālama ʻia ma 22 ° C, ʻoiai mālama ʻia nā kānaka maʻamau i ka mahana like a no ka manawa like ʻaʻole i alakaʻi i ke kuni.ʻokoʻa pili i ke kaumaha o ke kino.iole kaumaha.Ke hoʻohālikelike ʻia me nā mahana kokoke i ka thermoneutral a i ʻole ma ka lumi wela, ʻo ka ulu ʻana ma ka lumi wela ka hopena i ka DIO a i ʻole nā ​​ʻiole kaumaha maʻamau i ka meaʻai momona nui akā ʻaʻole i ka ʻai ʻiole kaumaha maʻamau e loaʻa iki ke kaumaha.kino.Kākoʻo ʻia e nā haʻawina ʻē aʻe17,18,19,20,21 akā ʻaʻole na nā mea a pau22,23.
ʻO ka hiki ke hana i ka microenvironment e hōʻemi i ka wela, ua manaʻo ʻia e hoʻololi i ka neutrality thermal i ka hema8, 12. Ma kā mākou noiʻi ʻana, ʻo ka hoʻohui ʻana o nā mea nesting a me ka hūnā i hoʻemi ʻia ka EE akā ʻaʻole i hopena i ka neutrality thermal a hiki i 28 ° C.No laila, ʻaʻole kākoʻo kā mākou ʻikepili i ka helu haʻahaʻa o ka thermoneutrality i nā ʻiole makua hoʻokahi-knee, me nā hale i hoʻonui ʻia i ke kaiapuni, he 26-28°C e like me ka hōʻike ʻana8,12, akā kākoʻo ia i nā haʻawina ʻē aʻe e hōʻike ana i ka thermoneutrality.nā mahana o 30°C i nā ʻiole haʻahaʻa haʻahaʻa7, 10, 24. No ka paʻakikī o nā mea, ua hōʻike ʻia ka helu thermoneutral i nā ʻiole ʻaʻole paʻa i ka lā no ka mea he haʻahaʻa i ka wā hoʻomaha (māmā), ma muli paha o ka haʻahaʻa o ka calorie. hana ma muli o ka hana a me ka thermogenesis i hoʻokomo ʻia i ka meaʻai.No laila, ma ka māhele māmā, ʻo ka helu haʻahaʻa o ka neutrality thermal e lilo i ~ 29 ° C, a ma ka manawa pōʻeleʻele, ~ 33 ° C25.
ʻO ka hope loa, ʻo ka pilina ma waena o ka wela a me ka pau ʻana o ka ikehu e hoʻoholo ʻia e ka wela wela.Ma kēia pōʻaiapili, ʻo ka lakio o ka ʻili a me ka leo he mea hoʻoholo koʻikoʻi o ka ʻike wela, e pili ana i ka hoʻoheheʻe ʻana o ka wela (kahi ʻili) a me ka hana wela (volume).Ma waho aʻe o ka ʻili, hoʻoholo ʻia ka hoʻoili wela e ka insulation (rate of heat transfer).I loko o ke kanaka, hiki i ka momona nui ke ho'ēmi i ka wela ma o ka hana 'ana i ka pale insulating a puni ka iwi kino, a ua mana'o 'ia he mea nui ka momona no ka ho'oku'u wela i nā 'iole, e ho'oha'aha'a ana i ka helu thermoneutral a me ka ho'ēmi 'ana i ka wela ma lalo o ka wela wela ( ka piʻi ʻana o ka piko).hoʻohālikelike ʻia me ka EE)12.ʻAʻole i hoʻolālā ʻia kā mākou aʻo ʻana e loiloi pololei i kēia pilina putative no ka mea ua hōʻiliʻili ʻia ka ʻikepili o ke kino i nā lā 9 ma mua o ka hōʻiliʻili ʻana o ka ʻikepili hoʻolimalima a no ka mea ʻaʻole paʻa ka momona i loko o ke aʻo ʻana.Eia nō naʻe, no ka mea he 30% haʻahaʻa haʻahaʻa EE ma ke kaumaha maʻamau a me nā ʻiole DIO ma 30 ° C ma mua o 22 ° C me ka liʻiliʻi o ka ʻokoʻa 5-fold i ka nui o ka momona, ʻaʻole kākoʻo kā mākou ʻikepili i ka mea momona e hāʻawi i ka insulation kumu.kumu, ma ka liʻiliʻi loa ʻaʻole i loko o ka pae wela i ʻimi ʻia.Ua like kēia me nā haʻawina ʻē aʻe i hoʻolālā maikaʻi ʻia e ʻimi i kēia4,24.I loko o kēia mau haʻawina, ua liʻiliʻi ka hopena insulating o ka momona, akā ua ʻike ʻia ka huluhulu e hāʻawi i ka 30-50% o ka nui insulation thermal4,24.Eia naʻe, i nāʻiole make, ua hoʻonui ka thermal conductivity ma kahi o 450% ma hope koke iho o ka make, e hōʻike ana he pono ka hopena insulating o ka hulu no nā hana physiological, me ka vasoconstriction, e hana.Ma waho aʻe o nā ʻano ʻokoʻa o ka hulu ma waena o nā ʻiole a me nā kānaka, hiki ke hoʻopili ʻia ka hopena insulating maikaʻi ʻole o ka momona i nā ʻiole e nā manaʻo penei: ʻO ka insulating factor o ka momona momona kanaka ka mea nui i hoʻopili ʻia e ka subcutaneous fat mass (mānoanoa)26,27.ʻO ka maʻamau i nā rodents E emi iho ma mua o 20% o ka nui o ka momona holoholona28.Eia kekahi, ʻaʻole paha he ʻano suboptimal ka nui o ka momona o ke kanaka, no ka mea, ua hoʻopaʻapaʻa ʻia ʻo ka hoʻomaikaʻi ʻana i ka wela wela e hoʻopau ʻia e ka piʻi ʻana o ka ʻili (a no laila ua hoʻonui ʻia ka wela) i ka piʻi ʻana o ka momona..
I nā ʻiole kaumaha maʻamau, ʻaʻole i loli ka nui o ka plasma hoʻokē ʻai o TG, 3-HB, cholesterol, HDL, ALT, a me AST i nā wela like ʻole no ka aneane 5 mau pule, no ka mea aia nā ʻiole i ke ʻano like o ke koena o ka ikehu.ua like ke kaumaha a me ke kino i ka pau ana o ke ao ana.E like me ka like o ka momona momona, ʻaʻohe ʻokoʻa i ka pae leptin plasma, ʻaʻole hoʻi i ka insulin hoʻokēʻai, C-peptide, a me ka glucagon.Loaʻa nā hōʻailona hou aʻe i nā ʻiole DIO.ʻOiai ʻaʻole i loaʻa i nā ʻiole ma 22°C ke koena o ka ikehu maikaʻi ʻole ma kēia mokuʻāina (ʻoiai ua loaʻa iā lākou ke kaumaha), i ka pau ʻana o ke aʻo ʻana ua ʻoi aku ka nui o ka ikehu ma mua o nā ʻiole i hānai ʻia ma 30 ° C, ma nā kūlana e like me nā ketone kiʻekiʻe.hana ʻia e ke kino (3-GB) a me ka emi ʻana o ka glycerol a me TG i ka plasma.Eia naʻe, ʻaʻole ʻike ʻia nā ʻokoʻa pili i ka wela i ka lipolysis ma muli o nā hoʻololi intrinsic i ka epididymal a i ʻole ka momona inguinal, e like me ka hoʻololi ʻana i ka hōʻike o ka adipohormone-responsive lipase, ʻoiai ʻo FFA a me glycerol i hoʻokuʻu ʻia mai ka momona i lawe ʻia mai kēia mau depot aia ma waena o Temperature. ua like nā pūʻulu me kekahi.ʻOiai ʻaʻole mākou i noiʻi i ka leo aloha i loko o ka noiʻi o kēia manawa, ua ʻike nā mea ʻē aʻe (e pili ana i ka helu o ka naʻau a me ke ʻano o ke kaomi arterial) pili linearly i ka wela ambient i nā ʻiole a ʻoi aku ka haʻahaʻa ma 30 ° C ma mua o 22 ° C 20% C No laila, hiki ke hana i ka lipolysis i loko o kā mākou noiʻi ʻana i nā ʻokoʻa pili i ka wela i ka leo aloha, akā no ka mea, ʻoi aku ka hoʻonui ʻana o ka leo aloha ma mua o ka pale ʻana i ka lipolysis, hiki i nā hana ʻē aʻe ke kūʻē i kēia emi ʻana o nā ʻiole moʻomeheu.ʻO ke kuleana kūpono i ka haki ʻana o ka momona o ke kino.Ka wela lumi.Eia kekahi, ʻo ka hapa o ka hopena stimulatory o ka leo aloha ma ka lipolysis i hoʻopili ʻia e ka inhibition ikaika o ka huna ʻana o ka insulin, e hōʻike ana i ka hopena o ka insulin interrupting supplementation ma lipolysis30, akā i kā mākou noiʻi ʻana, ʻo ka insulin plasma wikiwiki a me C-peptide sympathetic leo i nā mahana like ʻole. ʻaʻole lawa e hoʻololi i ka lipolysis.Akā, ua ʻike mākou ʻo nā ʻokoʻa o ke kūlana ikehu ka mea nui i kōkua i kēia mau ʻokoʻa i nā ʻiole DIO.ʻO nā kumu kumu e alakaʻi ai i ka hoʻoponopono ʻoi aku ka maikaʻi o ka ʻai ʻana i ka meaʻai me EE i nā ʻiole kaumaha maʻamau e pono e aʻo hou.Ma ka laulā, e hoʻomalu ʻia ka ʻai ʻana e ka homeostatic a me ka hedonic cues31,32,33.ʻOiai aia ka hoʻopaʻapaʻa e pili ana i kahi o nā hōʻailona ʻelua i ʻoi aku ka nui, 31,32,33 ua ʻike ʻia ʻo ka hoʻohana lōʻihi ʻana i nā meaʻai momona kiʻekiʻe e alakaʻi i ka ʻai ʻana i ka leʻaleʻa i pili ʻole i kekahi. homeostasis..- hoʻoponopono ʻia ka ʻai ʻana i ka meaʻai34,35,36.No laila, ʻo ka hoʻonui ʻana i ka hana hānai hedonic o nā ʻiole DIO i mālama ʻia me 45% HFD paha kekahi o nā kumu i kaulike ʻole ai kēia mau ʻiole i ka ʻai me ka EE.ʻO ka mea e mahalo ai, ua ʻike pū ʻia nā ʻokoʻa o ka ʻai a me nā hormone hoʻoponopono glucose koko i nā ʻiole DIO i mālama ʻia i ka mahana, akā ʻaʻole i nā ʻiole kaumaha maʻamau.I nā ʻiole DIO, piʻi ka pae leptin plasma me ka mahana a ua emi nā pae glucagon me ka mahana.ʻO ka nui o ka hiki ke hoʻololi pololei i kēia mau ʻokoʻa e pono ke aʻo hou ʻia, akā i ka hihia o ka leptin, ʻo ke koena o ka ikehu maikaʻi ʻole a no laila e hoʻohaʻahaʻa i ka momona momona i nā ʻiole ma 22 ° C he mea koʻikoʻi loa ia, ʻoiai ʻo ka momona momona a me ka plasma leptin. pili loa37.Eia naʻe, ʻoi aku ka paʻakikī o ka wehewehe ʻana i ka hōʻailona glucagon.E like me ka insulin, ua kāohi ikaika ʻia ka huna ʻana o ka glucagon e ka piʻi ʻana o ka leo aloha, akā ʻo ka leo aloha kiʻekiʻe i wānana ʻia i loko o ka pūʻulu 22 ° C, nona ka kiʻekiʻe o ka glucagon plasma kiʻekiʻe.ʻO ka insulin kekahi mea hoʻoponopono ikaika o ka glucagon plasma, a ʻo ke kūpaʻa o ka insulin a me ka maʻi diabetes type 2 e pili pū ana me ka hoʻokē ʻai a me ka hyperglucagonemia postprandial 38,39.Eia nō naʻe, ʻo nā ʻiole DIO i kā mākou aʻo ʻana he insulin insensitive nō hoʻi, no laila ʻaʻole hiki i kēia ke kumu nui i ka piʻi ʻana o ka hōʻailona glucagon i ka hui 22 ° C.Hoʻopili maikaʻi ʻia ka momona o ka ate me ka piʻi ʻana o ka glucagon plasma, ʻo ia hoʻi, hiki ke hoʻopili i ka pale ʻana o ka glucagon hepatic, hoʻemi i ka hana ʻana o ka urea, hoʻonui i ka nui o ka waikawa amino acid, a me ka hoʻonui ʻana i ka glucagon secretion 40,41. 42.Eia naʻe, no ka mea, ʻaʻole ʻokoʻa ka ʻokoʻa o ka glycerol a me TG ma waena o nā pūʻulu wela i kā mākou aʻo ʻana, ʻaʻole hiki ke lilo kēia i kumu kūpono i ka piʻi ʻana o ka plasma concentrations ma ka hui 22 ° C.He kuleana koʻikoʻi ka Triiodothyronine (T3) i ka helu metabolic holoʻokoʻa a me ka hoʻomaka ʻana o ka pale metabolic i ka hypothermia43,44.No laila, ʻo ka plasma T3 concentration, hiki ke hoʻomalu ʻia e nā mīkini i waena, hoʻonui ʻia ka 45,46 i nā ʻiole a me nā kānaka ma lalo o nā kūlana thermoneutral47, ʻoiai ʻoi aku ka liʻiliʻi o ka piʻi ʻana o nā kānaka, ʻoi aku ka predisposed i nā ʻiole.Kūlike kēia me ka lilo ʻana o ka wela i ke kaiapuni.ʻAʻole mākou i ana i ka plasma T3 concentrations i ka haʻawina o kēia manawa, akā ua emi paha ka nui ma ka hui 30 ° C, hiki ke wehewehe i ka hopena o kēia pūʻulu ma nā pae glucagon plasma, e like me kā mākou (hōʻano hou i ka Figure 5a) a me nā mea ʻē aʻe. Hoʻonui ʻo T3 i ka glucagon plasma ma ke ʻano hilinaʻi.Ua hōʻike ʻia nā hormones thyroid e hoʻoulu i ka hōʻike FGF21 i loko o ke ake.E like me ka glucagon, ua hoʻonui pū ʻia ka plasma FGF21 me ka plasma T3 concentrations (Supplementary Fig. 5b and ref. 48), akā i hoʻohālikelike ʻia me ka glucagon, FGF21 plasma concentrations i kā mākou haʻawina ʻaʻole i hoʻopilikia ʻia e ka mahana.ʻO nā kumu kumu o kēia ʻokoʻa e pono ai ke aʻo hou ʻana, akā pono ka hoʻokomo ʻia ʻana o ka FGF21 i alakaʻi ʻia e T3 ma nā pae kiʻekiʻe o ka hōʻike T3 i hoʻohālikelike ʻia i ka pane glucagon hoʻokele T3 i ʻike ʻia (Supplementary Fig. 5b).
Ua hōʻike ʻia ʻo HFD i pili ikaika me ka hoʻomanawanui glucose impaired a me ka pale ʻana o ka insulin (hōʻailona) i nā ʻiole i hānai ʻia ma 22°C.Eia naʻe, ʻaʻole i pili ʻia ka HFD me ka hoʻomanawanui ʻana i ka glucose impaired a i ʻole ke kūpaʻa ʻana o ka insulin i ka wā e ulu ai i kahi ʻano thermoneutral (i wehewehe ʻia ma ʻaneʻi ʻo 28 °C) 19 .I kā mākou aʻo ʻana, ʻaʻole i hoʻopili hou ʻia kēia pilina ma nā ʻiole DIO, akā ʻo nā ʻiole kaumaha maʻamau i mālama ʻia ma 30 ° C i hoʻomaikaʻi nui i ka hoʻomanawanui glucose.ʻO ke kumu o kēia ʻokoʻa e pono ai ka noiʻi hou ʻana, akā hiki ke hoʻololi ʻia e ka ʻoiaʻiʻo ʻo nā ʻiole DIO i kā mākou noiʻi ʻana i ka insulin resistant, me ka hoʻokē ʻai plasma C-peptide concentrations a me ka insulin concentrations 12-20 manawa kiʻekiʻe ma mua o nāʻiole kaumaha maʻamau.a i loko o ke koko ma ka ʻōpū ʻole.ka nui o ka glucose ma kahi o 10 mM (e pili ana i 6 mM ma ke kaumaha o ke kino maʻamau), me he mea lā e waiho ana i kahi puka makani liʻiliʻi no nā hopena maikaʻi o ka ʻike ʻana i nā kūlana thermoneutral e hoʻomaikaʻi ai i ka hoʻomanawanui glucose.ʻO kahi kumu hoʻohālikelike paha, no nā kumu kūpono, lawe ʻia ʻo OGTT ma ka lumi wela.No laila, ʻike ʻia nā ʻiole i noho ʻia ma nā wela kiʻekiʻe aʻe i ka haʻalulu haʻahaʻa haʻahaʻa, hiki ke hoʻopilikia i ka lawe ʻana o ka glucose.Eia nō naʻe, ma muli o ka hoʻokē ʻai ʻana o ka glucose koko like ʻole i nā pūʻulu wela like ʻole, ʻaʻole i hoʻololi nui ʻia nā hopena i ka hopena.
E like me ka mea i ʻōlelo ʻia ma mua, ua hōʻike ʻia i kēia manawa ʻo ka hoʻonui ʻana i ka mahana o ka lumi e hoʻemi i kekahi mau hopena i ke koʻikoʻi anu, kahi e nīnau ai i ka hoʻololi ʻana o ka ʻikepili ʻiole i nā kānaka.Akā naʻe, ʻaʻole maopopo i ka mahana kūpono no ka mālama ʻana i nā ʻiole e hoʻohālike i ka physiology kanaka.Hiki ke hoʻopili ʻia ka pane i kēia nīnau e ke kahua aʻo a me ka hopena e aʻo ʻia.ʻO kahi laʻana o kēia ka hopena o ka meaʻai i ka hōʻiliʻili ʻana o ka momona o ke akepaʻa, ka ʻae ʻana i ka glucose a me ka pale ʻana o ka insulin19.Ma ke ʻano o ka hoʻolilo ʻana i ka ikehu, manaʻo kekahi poʻe noiʻi ʻo ka thermoneutrality ka wela maikaʻi loa no ka hānai ʻana, ʻoiai ke koi nei ke kanaka i ka liʻiliʻi o ka ikehu e mālama ai i ko lākou kino kino, a wehewehe lākou i kahi mahana o ka ʻūhā no nā ʻiole makua he 30°C7,10.Manaʻo nā mea noiʻi ʻē aʻe he 23-25 ​​° C ka mahana i hoʻohālikelike ʻia me nā ʻiole makua ma kekahi kuli, no ka mea, ʻike lākou i ka thermoneutrality he 26-28 ° C a ma muli o ke emi ʻana o ke kanaka ma kahi o 3 ° C.ʻO ko lākou wela haʻahaʻa haʻahaʻa, i wehewehe ʻia ma ʻaneʻi ʻo 23 ° C, he 8.12 iki.Kūlike kā mākou haʻawina me kekahi mau haʻawina ʻē aʻe e ʻōlelo ana ʻaʻole i loaʻa ka neutrality thermal ma 26-28°C4, 7, 10, 11, 24, 25, e hōʻike ana he haʻahaʻa loa ka 23-25°C.ʻO kekahi mea nui e noʻonoʻo ai e pili ana i ka mahana o ka lumi a me ka thermoneutrality i nā ʻiole he hale hoʻokahi a hui pū paha.I ka noho ʻana o nā ʻiole ma nā hui ma mua o ka hoʻokahi, e like me kā mākou haʻawina, ua hoʻemi ʻia ka ʻike wela, ma muli paha o ka lehulehu o nā holoholona.Eia nō naʻe, aia nō ka mahana o ka lumi ma lalo o ka LTL o 25 i ka wā i hoʻohana ʻia ai ʻekolu pūʻulu.Malia paha ʻo ka ʻokoʻa interspecies koʻikoʻi ma kēia ʻano ʻo ia ke koʻikoʻi nui o ka hana BAT ma ke ʻano he pale i ka hypothermia.No laila, ʻoiai ʻo nā ʻiole i uku nui ʻia no kā lākou pohō calorie kiʻekiʻe ma o ka hoʻonui ʻana i ka hana BAT, ʻoi aku ma luna o 60% EE ma 5 ° C wale nō, 51,52 ʻoi aku ka kiʻekiʻe o ka hana BAT kanaka iā EE, ʻoi aku ka liʻiliʻi.No laila, ʻo ka hoʻemi ʻana i ka hana BAT he ala nui ia e hoʻonui ai i ka unuhi kanaka.He paʻakikī ka hoʻoponopono o ka hana BAT akā ua hoʻopili pinepine ʻia e nā hopena i hui ʻia o ka hoʻoulu ʻana adrenergic, thyroid hormones a me ka UCP114,54,55,56,57 expression.Hōʻike kā mākouʻikepili e pono ke hoʻokiʻekiʻeʻia ka mahana ma luna o 27.5 ° C i ka hoʻohālikelikeʻana i nāʻiole ma 22 ° C i mea eʻike ai i nāʻokoʻa o ka'ōlelo o nā genes BAT kuleana no ka hana / hana.Eia naʻe,ʻo nāʻokoʻa i loaʻa ma waena o nā hui ma 30 a me 22 ° Cʻaʻole i hōʻike mau i ka piʻiʻana o ka hana BAT ma ka hui 22 ° C no ka mea, ua hoʻohaʻahaʻaʻiaʻo Ucp1, Adrb2 a me Vegf-a i ka hui 22 ° C.ʻO ke kumu o kēia mau hopena i manaʻo ʻole ʻia e hoʻoholo ʻia.ʻO kekahi mea hiki ke hoʻonui ʻia ka hōʻike ʻana ʻaʻole i hōʻike i kahi hōʻailona o ke kiʻekiʻe o ka lumi lumi, akā he hopena koʻikoʻi o ka neʻe ʻana iā lākou mai 30 ° C a 22 ° C i ka lā o ka wehe ʻana (ua ʻike nā ʻiole i kēia 5-10 mau minuke ma mua o ka haʻalele ʻana) .).
ʻO kahi palena maʻamau o kā mākou noiʻi ʻana ʻo mākou i aʻo wale i nā ʻiole kāne.Hōʻike nā noiʻi ʻē aʻe he manaʻo koʻikoʻi paha ke kāne i kā mākou mau hōʻailona mua, no ka mea, ʻoi aku ka maʻalahi o ka wela o nā ʻiole wahine kuli hoʻokahi ma muli o ke kiʻekiʻe o ka wela wela a me ka mālama ʻana i nā wela kumu.Eia kekahi,ʻo nāʻiole wahine (ma ka HFD) i hōʻike i ka hui nui o ka hoʻohanaʻana i ka ikehu me EE ma 30 °C i ka hoʻohālikelikeʻana i nāʻiole kāne iʻai i nāʻiole o ka wahine like (20 °C i kēia hihia) 20.No laila, i nā ʻiole wahine, ʻoi aku ka kiʻekiʻe o ka hopena subthermonetral, akā ua like ke ʻano like me nā ʻiole kāne.Ma kā mākou noiʻi ʻana, ua kālele mākou i nā ʻiole kāne kuli hoʻokahi, ʻoiai ʻo ia nā kūlana e mālama ʻia ai ka hapa nui o nā haʻawina metabolic e nānā ana iā EE.ʻO kekahi palena ʻē aʻe o kā mākou noiʻi ʻana ʻo ia ka ʻai like ʻana o nā ʻiole i loko o ke aʻo ʻana, kahi i kāpae ʻia ai ke aʻo ʻana i ke koʻikoʻi o ka mahana o ka lumi no ka hiki ke hoʻololi ʻia (e like me ke ana ʻana i nā loli RER no nā loli meaʻai i nā ʻano macronutrient like ʻole).i nā ʻiole wahine a me nā kāne i mālama ʻia ma 20°C i hoʻohālikelike ʻia me nā ʻiole i mālama ʻia ma 30°C.
I ka hopena, hōʻike kā mākou haʻawina, e like me nā haʻawina ʻē aʻe, ʻoi aku ka thermoneutral o nā ʻiole kaumaha maʻamau ma mua o ka 27.5 ° C.Eia hou, ke hōʻike nei kā mākou haʻawina ʻaʻole ʻo ka momona he kumu insulating nui i nā ʻiole me ke kaumaha maʻamau a i ʻole DIO, ka hopena i ka like like: EE ratios ma DIO a me nā ʻiole kaumaha maʻamau.ʻOiai kaʻaiʻana o nāʻiole kaumaha maʻamau i kūlike me ka EE a pēlā e mālama ai i ke kaumaha o ke kino paʻa ma luna o ke ana wela holoʻokoʻa, ua like kaʻaiʻana o nāʻiole DIO i nā mahana likeʻole, e hopena i ka lakene kiʻekiʻe o nāʻiole ma 30 ° C .ma 22°C ua loaʻa ke kaumaha o ke kino.Ma ke ʻano holoʻokoʻa, pono nā haʻawina ʻōnaehana e nānā ana i ke koʻikoʻi o ka noho ʻana ma lalo o nā mahana thermoneutral ma muli o ka ʻike pinepine ʻole ʻia ma waena o ka ʻiole a me nā haʻawina kanaka.No ka laʻana, ma nā haʻawina obesity, ʻo ka wehewehe ʻana no ka unuhi ʻilihune maʻamau ma muli o ka hana maʻamau ʻana o nā haʻawina hoʻoemi paona murine i nā holoholona i hoʻoluhi ʻia i ke anu i mālama ʻia ma ka lumi wela ma muli o ko lākou hoʻonui EE.ʻO ke kaumaha o ke kaumaha ke hoʻohālikelike ʻia me ke kaumaha o ke kino i manaʻo ʻia o ke kanaka, ʻoiai inā pili ke ʻano o ka hana i ka hoʻonui ʻana i ka EE ma o ka hoʻonui ʻana i ka hana o BAP, ʻoi aku ka ikaika a hoʻoikaika ʻia ma ka lumi wela ma mua o 30 ° C.
E like me ka Danish Animal Experimental Law (1987) a me ka National Institutes of Health (Publication No. 85-23) a me ka European Convention for the Protection of Vertebrate used for Experimental and Other Scientific Purposes (Council of Europe No. 123, Strasbourg , 1985).
Ua loaʻa nā ʻiole kāne C57BL/6J he iwakālua mau pule mai Janvier Saint Berthevin Cedex, Farani, a ua hāʻawi ʻia i ka ad libitum standard chow (Altromin 1324) a me ka wai (~ 22 ° C) ma hope o ka hola 12:12 hola māmā: pōʻeleʻele.wela lumi.Ua loaʻa nāʻiole kāne DIO (20 wiki) mai ka mea hoʻolako hoʻokahi a ua hāʻawiʻia i ka ad libitum i kahi 45% kiʻekiʻe momona (Cat. No. D12451, Research Diet Inc., NJ, USA) a me ka wai ma lalo o nā kūlana hānai.Hoʻololi ʻia nā ʻiole i ke kaiapuni i hoʻokahi pule ma mua o ka hoʻomaka ʻana o ke aʻo ʻana.ʻElua lā ma mua o ka hoʻololi ʻana i ka ʻōnaehana calorimetry indirect, ua kaupaona ʻia nā ʻiole, i hoʻopaʻa ʻia i ka scan MRI (EchoMRITM, TX, USA) a māhele ʻia i ʻehā mau pūʻulu e pili ana i ke kaumaha o ke kino, ka momona a me ke kaumaha o ke kino maʻamau.
Hōʻike ʻia kahi kiʻi paʻi kiʻi o ka hoʻolālā haʻawina ma ka Figure 8. Ua hoʻoneʻe ʻia nā ʻiole i kahi ʻōnaehana calorimetry indirect i pani ʻia a mālama ʻia i ka mahana ma Sable Systems Internationals (Nevada, USA), kahi i hoʻokomo ʻia nā mea nānā i ka maikaʻi o ka meaʻai a me ka wai a me kahi kiʻi Promethion BZ1 i hoʻopaʻa ʻia. nā pae hana ma ke ana ʻana i ka haki ʻana o ke kukui.XYZ.Hoʻokomo ʻia nā ʻiole (n = 8) i kēlā me kēia ma 22, 25, 27.5, a i ʻole 30 ° C me ka hoʻohana ʻana i kahi moena akā ʻaʻohe hale hoʻomaha a me nā mea nesting ma kahi kukui 12:12-hola: pōʻeleʻele (mālamalama: 06:00–18:00) .2500ml/min.Hoʻomaʻamaʻa ʻia nā ʻiole no 7 mau lā ma mua o ke kau inoa ʻana.Ua hōʻiliʻili ʻia nā hoʻopaʻa leo ʻehā lā ma ka lālani.Ma hope mai, mālama ʻia nā ʻiole ma nā mahana like ʻole ma 25, 27.5, a me 30 ° C no nā lā he 12 hou, a ma hope iho ua hoʻohui ʻia nā concentrates cell e like me ka mea i wehewehe ʻia ma lalo nei.I kēia manawa, mālama ʻia nā pūʻulu ʻiole i 22 ° C i kēia mahana no ʻelua mau lā hou (e hōʻiliʻili i ka ʻikepili baseline hou), a laila hoʻonui ʻia ka mahana ma nā ʻanuʻu o 2 ° C i kēlā me kēia lā i ka hoʻomaka ʻana o ka māhele māmā ( 06:00) a hiki i 30 °C Ma hope o kēlā, ua hoʻohaʻahaʻa ʻia ka mahana i 22°C a ua hōʻiliʻili ʻia ka ʻikepili no nā lā ʻelua.Ma hope o ʻelua mau lā hou o ka hoʻopaʻa ʻana ma 22 ° C, ua hoʻohui ʻia nā ʻili i nā cell āpau i nā mahana āpau, a hoʻomaka ka hōʻiliʻili ʻikepili i ka lua o ka lā (lā 17) a no nā lā ʻekolu.Ma hope o kēlā (lā 20), hoʻohui ʻia nā mea nesting (8-10 g) i nā cell āpau i ka hoʻomaka ʻana o ka pōʻai māmā (06:00) a ua hōʻiliʻili ʻia nā ʻikepili no nā lā ʻekolu.No laila, i ka pau ʻana o ke aʻo ʻana, mālama ʻia nā ʻiole ma 22 ° C i kēia mahana no 21/33 mau lā a ma 22 ° C no nā lā 8 hope loa, ʻoiai ʻo nā ʻiole i nā mahana ʻē aʻe i mālama ʻia i kēia mahana no 33 mau lā./33 lā.Ua hānai ʻia nā ʻiole i ka wā aʻo.
ʻO ke kaumaha maʻamau a me nāʻiole DIO i hahai i nā kaʻina hana like.I ka lā -9, kaupaona ʻia nā ʻiole, nānā ʻia ka MRI, a māhele ʻia i nā hui e like me ke kaumaha o ke kino a me ke ʻano o ke kino.Ma ka lā -7, ua hoʻoneʻe ʻia nā ʻiole i kahi ʻōnaehana calorimetry indirect i hoʻopaʻa ʻia e ka SABLE Systems International (Nevada, USA).Hoʻokomo ʻia nā ʻiole me nā mea moe akā ʻaʻohe mea hoʻomoe a i ʻole nā ​​​​mea hoʻolulu.Hoʻonohonoho ʻia ka mahana i 22, 25, 27.5 a i ʻole 30 °C.Ma hope o hoʻokahi pule o ka acclimatization (nā lā -7 a hiki i ka 0, ʻaʻole i hoʻopilikia ʻia nā holoholona), ua hōʻiliʻili ʻia nā ʻikepili i nā lā ʻehā (lā 0-4, ʻike i hōʻike ʻia ma FIGS. 1, 2, 5).Ma hope mai, mālama ʻia nā ʻiole ma 25, 27.5 a me 30 ° C ma lalo o nā kūlana mau a hiki i ka lā 17.I ka manawa like, ua hoʻonui ʻia ka mahana o ka hui 22 ° C i nā manawa o 2 ° C i kēlā me kēia lā ma o ka hoʻoponopono ʻana i ka pōʻai wela (06:00 h) i ka hoʻomaka ʻana o ka mālamalama (hōʻike ʻia nā ʻikepili ma Fig. 1). .Ma ka lā 15, ua hāʻule ka mahana i 22 ° C a ua hōʻiliʻili ʻia nā lā ʻelua o ka ʻikepili no ka hāʻawi ʻana i ka ʻikepili kumu no ka mālama ʻana ma hope.Hoʻohui ʻia nā ʻili i nā ʻiole a pau i ka lā 17, a ua hoʻohui ʻia nā mea hana pūnana i ka lā 20 (Fig. 5).I ka lā 23rd, ua kaupaona ʻia nā ʻiole a kau ʻia i ka scan MRI, a laila waiho wale ʻia no 24 mau hola.Ma ka lā 24, hoʻokē ʻai nā ʻiole mai ka hoʻomaka ʻana o ka photoperiod (06:00) a loaʻa iā OGTT (2 g / kg) ma 12:00 (6-7 mau hola o ka hoʻokē ʻai).Ma hope mai, ua hoʻihoʻi ʻia nā ʻiole i ko lākou kūlana SABLE ponoʻī a euthanized i ka lua o ka lā (lā 25).
ʻO nāʻiole DIO (n = 8) i hahai i ka protocol like me nāʻiole kaumaha maʻamau (e like me ka mea i ho'ākākaʻia ma luna a me ka Figure 8).Mālama nā ʻiole i ka 45% HFD i loko o ka hoʻokolohua hoʻolimalima ikehu.
ʻO VO2 a me VCO2, a me ke kaomi mahu wai, ua hoʻopaʻa ʻia ma ke alapine o 1 Hz me ka manawa maʻamau o 2.5 min.Ua hōʻiliʻili ʻia ka ʻai a me ka wai e ka hoʻopaʻa mau ʻana (1 Hz) o ke kaumaha o nā ʻeke ʻai a me ka wai.Ua hōʻike ʻia kahi hoʻonā o 0.002 g ka nānā ʻana i ka maikaʻi.Ua hoʻopaʻa ʻia nā pae haʻawina me ka nānā ʻana i ka 3D XYZ beam array monitor, hōʻiliʻili ʻia ka ʻikepili ma kahi hoʻonā kūloko o 240 Hz a hōʻike ʻia i kēlā me kēia kekona no ka helu ʻana i ka mamao holoʻokoʻa (m) me ka hoʻonā spatial kūpono o 0.25 knm.Ua hana ʻia ka ʻikepili me Sable Systems Macro Interpreter v.2.41, e helu ana i ka EE a me ka RER a me ka kānana ʻana i nā mea waho (e laʻa, nā hanana pāʻina hoʻopunipuni).Hoʻonohonoho ʻia ka unuhi ʻōlelo macro e hoʻopuka i ka ʻikepili no nā ʻāpana āpau i kēlā me kēia ʻelima mau minuke.
Ma waho aʻe o ka hoʻoponopono ʻana i ka EE, hiki ke hoʻoponopono ʻia ka mahana ambient i nā ʻano ʻē aʻe o ka metabolism, me ka postprandial glucose metabolism, ma ka hoʻoponopono ʻana i ka huna ʻana o nā hormones-metabolizing glucose.No ka hoʻāʻo ʻana i kēia kuhiakau, ua hoʻopau hope mākou i kahi haʻawina wela o ke kino ma o ka hoʻonāukiuki ʻana i nā ʻiole kaumaha maʻamau me kahi haʻahaʻa glucose waha DIO (2 g/kg).Hōʻike ʻia nā ʻano hana i nā mea kikoʻī.
I ka pau ʻana o ke aʻo ʻana (lā 25), hoʻokē ʻai ʻia nā ʻiole no 2-3 mau hola (e hoʻomaka ana ma 06:00), hoʻomaʻamaʻa ʻia me ka isoflurane, a hoʻokahe piha ʻia e ka retroorbital venipuncture.ʻO ka helu ʻana o nā lipid plasma a me nā hormones a me nā lipids i loko o ke ake i wehewehe ʻia ma nā Mea Hoʻohui.
No ka noiʻi ʻana inā hoʻololi ka wela o ka pūpū i nā loli intrinsic i ka ʻiʻo adipose e pili ana i ka lipolysis, ua ʻoki pololei ʻia ka ʻiʻo adipose inguinal a me ka epididymal mai nā ʻiole ma hope o ka pae hope o ke koko.Ua hana ʻia nā ʻili me ka hoʻohana ʻana i ka ex vivo lipolysis assay i hōʻike ʻia ma nā ʻano hoʻohui.
Ua hōʻiliʻili ʻia ka ʻiʻo adipose brown (BAT) i ka lā o ka pau ʻana o ke aʻo ʻana a hana ʻia e like me ka wehewehe ʻana i nā ʻano hana hoʻohui.
Hōʻike ʻia ka ʻikepili ma ke ʻano he ± SEM.Ua hana ʻia nā kiʻi ma GraphPad Prism 9 (La Jolla, CA) a ua hoʻoponopono ʻia nā kiʻi ma Adobe Illustrator (Adobe Systems Incorporated, San Jose, CA).Ua loiloi ʻia ke koʻikoʻi o ka helu helu ma GraphPad Prism a hoʻāʻo ʻia e ka hoʻāʻo t-pālua, nā ana hou ʻana i hoʻokahi ala/ʻelua ʻaoʻao ANOVA a ukali ʻia e ka hoʻohālikelike hoʻohālikelike lehulehu a Tukey, a i ʻole ANOVA i hoʻopaʻa ʻole ʻia a ukali ʻia e ka hōʻike hoʻohālikelike lehulehu a Tukey e like me ka mea e pono ai.Ua hōʻoia ʻia ka puʻunaue Gaussian o ka ʻikepili e ka D'Agostino-Pearson normality test ma mua o ka hoʻāʻo ʻana.Hōʻike ʻia ka nui o ka laʻana ma ka ʻāpana e pili ana i ka ʻāpana "Results", a me ka moʻolelo.Ua wehewehe ʻia ka hana hou ʻana e like me ke ana i lawe ʻia ma ka holoholona hoʻokahi (ma vivo a i ʻole ma kahi hāpana kiko).Ma ke ʻano o ka reproducibility ʻikepili, ua hōʻike ʻia kahi hui ma waena o ka hoʻolilo ikehu a me ka mahana o ka hihia ma nā haʻawina kūʻokoʻa ʻehā me ka hoʻohana ʻana i nā ʻiole like ʻole me kahi hoʻolālā noiʻi like.
Loaʻa nā protocol hoʻokolohua kikoʻī, nā mea waiwai, a me nā ʻikepili maka ma ke noi kūpono mai ka mea kākau alakaʻi Rune E. Kuhre.ʻAʻole i hoʻopuka kēia haʻawina i nā reagent kūʻokoʻa hou, nā laina holoholona/kelepona transgenic, a i ʻole ka ʻikepili sequencing.
No ka ʻike hou aku e pili ana i ka hoʻolālā haʻawina, e ʻike i ka abstract Nature Research Report i pili i kēia ʻatikala.
Hana ʻia nā ʻikepili a pau i pakuhi.Ua waiho ʻia ʻo 1-7 ma ka waihona waihona ʻikepili Science, helu komo: 1253.11.sciencedb.02284 a i ʻole https://doi.org/10.57760/sciencedb.02284.Hiki ke hoʻouna ʻia nā ʻikepili i hōʻike ʻia ma ESM iā Rune E Kuhre ma hope o ka hoʻāʻo kūpono.
Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Nā holoholona Laboratory e like me nā kumu hoʻohālike o ka momona kanaka. Nilsson, C., Raun, K., Yan, FF, Larsen, MO & Tang-Christensen, M. Nā holoholona Laboratory e like me nā kumu hoʻohālike o ka momona kanaka.Nilsson K, Raun K, Yang FF, Larsen MO.a me Tang-Christensen M. Nā holoholona Laboratory ma ke ʻano he kumu hoʻohālike o ka momona kanaka. 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. Nā holoholona hoʻokolohua ma ke ʻano he kumu hoʻohālike no ke kanaka.Nilsson K, Raun K, Yang FF, Larsen MO.a me Tang-Christensen M. Nā holoholona Laboratory ma ke ʻano he kumu hoʻohālike o ka momona i loko o ke kanaka.Acta Pharmacology.karaima 33, 173–181 (2012).
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Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. ʻAʻohe hopena insulating o ka momona. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. ʻAʻohe hopena insulating o ka momona.Fischer AW, Chikash RI, von Essen G., Cannon B., a me Nedergaard J. ʻAʻohe hopena kaʻawale o ka momona. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. 肥胖没有绝缘作用。 Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. Ожирение не имеет изолирующего эффекта. Fischer, AW, Csikasz, RI, von Essen, G., Cannon, B. & Nedergaard, J. ʻAʻohe hopena kaʻawale o ka momona.ʻAe.J. Pilikino.endocrine.metabolism.311, E202–E213 (2016).
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Fischer, AW, Cannon, B. & Nedergaard, J. ʻO nā mahana kūpono o ka hale no nāʻiole e hoʻohālike i ke kaiapuni wela o nā kānaka: He haʻawina hoʻokolohua. Fischer, AW, Cannon, B. & Nedergaard, J. ʻO nā mahana kūpono o ka hale no nāʻiole e hoʻohālike i ke kaiapuni wela o nā kānaka: He haʻawina hoʻokolohua.Fischer, AW, Cannon, B., a me Nedergaard, J. ʻO nā mahana maikaʻi loa o ka hale no nāʻiole e hoʻohālike i ke kaiapuni wela kanaka: He haʻawina hoʻokolohua. 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.ʻO Fisher AW, Cannon B., a me Nedergaard J. ʻO ka mahana kūpono o ka hale no nāʻiole e hoʻohālike ana i ke kaiapuni wela kanaka: He haʻawina hoʻokolohua.Moore.metabolism.7, 161–170 (2018).
Keijer, J., Li, M. & Speakman, JR He aha ka mahana hale maikaʻi loa e unuhi i nā hoʻokolohua ʻiole i nā kānaka? Keijer, J., Li, M. & Speakman, JR He aha ka mahana hale maikaʻi loa e unuhi i nā hoʻokolohua ʻiole i nā kānaka?Keyer J, Lee M a me Speakman JR He aha ka wela lumi maikaʻi loa no ka hoʻoili ʻana i nā hoʻokolohua ʻiole i ke kanaka? 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 a me Speakman JR He aha ka wela o ka pūpū maikaʻi loa no ka hoʻoili ʻana i nā hoʻokolohua ʻiole i ke kanaka?Moore.metabolism.25, 168–176 (2019).
Seeley, RJ & MacDougald, OA Mice ma ke ʻano he hoʻohālike hoʻokolohua no ka physiology kanaka: i ka wā e pili ana i kekahi mau degere i ka mahana o ka hale. Seeley, RJ & MacDougald, OA Mice ma ke ʻano he hoʻohālike hoʻokolohua no ka physiology kanaka: i ka wā e pili ana i kekahi mau degere i ka mahana o ka hale. Seeley, RJ & MacDougald, OA Мыши как экспериментальные модели для физиологии человека: когда несколько градусов и жичлище Seeley, RJ & MacDougald, OA Mice ma ke ʻano he hoʻohālike hoʻokolohua no ka physiology kanaka: i ka wā e hoʻololi ai kekahi mau degere i loko o kahi hale. Seeley, RJ & MacDougald, OA 小鼠作为人类生理学的实验模型：当几度的住房温度很重要时。 Seeley, RJ & MacDougald, OA МышTи EPYley, RJ & Mat & T MachogAt-кисия: нод тзавемино Seeley, RJ & MacDougald, ʻOA ʻiole ma ke ʻano he hoʻohālike hoʻokolohua o ka physiology kanaka: i ka wā e pono ai kekahi mau degere o ka wela o ka lumi.ʻO ka metabolism ʻāina.3, 443–445 (2021).
Fischer, AW, Cannon, B. & Nedergaard, J. ʻO ka pane i ka nīnau "He aha ka mahana o ka hale maikaʻi loa e unuhi i nā hoʻokolohua ʻiole i nā kānaka?" Fischer, AW, Cannon, B. & Nedergaard, J. ʻO ka pane i ka nīnau "He aha ka mahana o ka hale maikaʻi loa e unuhi i nā hoʻokolohua ʻiole i nā kānaka?" Fischer, AW, Cannon, B. & Nedergaard, J. Pane i ka nīnau "He aha ka lumi wela maikaʻi loa no ka hoʻololi ʻana i nā hoʻokolohua ʻiole i ke kanaka?" 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.ʻO Fisher AW, Cannon B., a me Nedergaard J. Pane i ka nīnau "He aha ka mahana o ka pūpū maikaʻi loa no ka hoʻoili ʻana i nā hoʻokolohua ʻiole i ke kanaka?"ʻAe: thermoneutral.Moore.metabolism.26, 1-3 (2019).