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論文名稱: 過度表現脂締素受體一型抑制小鼠棕色與米色脂肪之活性 ... 語文別: 英文 ... 因此，本研究發現AdipoR1減少冷刺激誘導下棕色脂肪與米色脂肪之生熱 ... 資料載入處理中... 跳到主要內容 臺灣博碩士論文加值系統 ::: 網站導覽| 首頁| 關於本站| 聯絡我們| 國圖首頁| 常見問題| 操作說明 English |FB專頁 |Mobile 免費會員 登入| 註冊 功能切換導覽列 (165.22.106.144)您好！臺灣時間：2022/01/0522:15 字體大小：       ::: 詳目顯示 recordfocus 第1筆/ 共1筆  /1頁 論文基本資料 摘要 外文摘要 目次 參考文獻 論文連結 QRCode 本論文永久網址: 複製永久網址Twitter研究生:陳郁仁研究生(外文):Yu-JenChen論文名稱:過度表現脂締素受體一型抑制小鼠棕色與米色脂肪之活性論文名稱(外文):Overexpressionofadiponectinreceptor1inhibitsbrownandbeigeadiposetissueactivityinmice指導教授:丁詩同指導教授(外文):Shih-TorngDing口試委員:歐柏榮、陳洵一、林劭品、林原佑、余祺口試委員(外文):Bor-RungOu、Shuen-EiChen、Shau-PingLin、Yuan-YuLin、ChiYu口試日期:2021-01-28學位類別:博士校院名稱:國立臺灣大學系所名稱:生物科技研究所學門:生命科學學門學類:生物科技學類論文種類:學術論文論文出版年:2021畢業學年度:109語文別:英文論文頁數:148中文關鍵詞:脂締素、脂締素受體一型、米色脂肪、棕色脂肪、正子掃描、生熱作用、生熱蛋白一型外文關鍵詞:adiponectin、adiponectinreceptor1、beigeadiposetissue、brownadiposetissue、cold-inducedthermogenesis、PET/CTscintigraphy、uncouplingprotein1(UCP1)DOI:10.6342/NTU202100596相關次數: 被引用:0點閱:61評分:下載:0書目收藏:0 成人與小鼠具顯而易見之棕色脂肪，且經由冷刺激下，某些白色脂肪部位可發現具類似棕色脂肪之細胞，此過程稱為白色脂肪棕色化(whitefatbrowning)或該棕色化之白色脂肪細胞被稱作米色脂肪細胞(beigeadipocyte)。

活化棕色脂肪或增加白色脂肪棕色化/米色脂肪可增加產熱以促進能量消耗，具抵抗肥胖或治療糖尿病之潛能。

脂締素(adiponectin)為脂肪組織分泌之細胞激素，可調控全身代謝。

於高脂飼糧下，脂締素可藉由增加白色脂肪堆積以減少游離脂肪酸於其他器官之傷害與堆積，進而改善肥胖造成之胰島素阻抗。

然而，脂締素與其受體(adiponectinreceptors)對冷刺激下棕色脂肪之活性與白色脂肪棕色化之功能仍未全然了解。

首先，本實驗先改良脂肪幹細胞分離之流程，增加產量與效率，並且建立條件可以分化出白色與米色脂肪細胞以進行後續實驗。

另外，此研究並建立FVB小鼠品系下，冷刺激對該FVB品系小鼠，低溫處理之強度及時間長度。

接著利用此條件探討野生型(wild-type)小鼠與基因轉殖小鼠大量表現脂締素受體一型(adiponectinreceptor1;AdipoR1)，於冷刺激下棕色脂肪與白色脂肪棕色化之活性與功能。

本研究利用3D正子掃描(positronemissiontomography/computedtomography,PET/CTscanning)發現，AdipoR1小鼠於冷刺激下葡萄糖之攝入較WT小鼠少，棕色脂肪與米色脂肪之脂肪細胞大小較大，並有小鼠全身體表溫度或棕色脂肪部位表面溫度較低之情形，此現象皆顯示AdipoR1小鼠產熱功能可能較低。

另外，棕色或米色脂肪組織中生熱蛋白基因(uncouplingprotein1,Ucp1)與棕色脂肪標記(brownadipocytemarker)基因、棕色脂肪細胞粒線體基因標記、脂肪分解基因、脂肪氧化基因於棕色或米色脂肪組織中也較WT小鼠低。

此外，AdipoR1小鼠所分離出白色脂肪幹細胞分化之米色脂肪細胞，其產熱基因Ucp1與棕色脂肪標記基因、棕色脂肪細胞粒線體基因標記基因，皆較WT小鼠之脂肪幹細胞分化之米色脂肪低。

因此，本研究發現AdipoR1減少冷刺激誘導下棕色脂肪與米色脂肪之生熱功能(cold-inducedthermogenesis)，調節脂締素或其受體功能或調控其下游途徑可能為日後肥胖與相關疾病治療之契機。

Adulthumansandmicepossesssignificantclassicalbrownadiposetissues(BAT)and,uponcold-induction,acquirebrown-likeadipocytesincertaindepotsofwhiteadiposetissues(WAT),knownasbeigeadiposetissuesorWATbrowning/beiging.ActivationofthermogenicclassicalBATorWATbeigingtogenerateheatlimitsdiet-inducedobesityortype-2diabetesinmice.Adiponectinisabeneficialadipokineresistingdiabetes,andcausing“healthyobese”byincreasingWATexpansiontolimitlipotoxicityinothermetabolictissuesduringhigh-fatfeeding.However,theroleofitsreceptorsandsignaling,especiallyadiponectinreceptor1(AdipoR1),oncold-inducedthermogenesisinvivoinBATandinWATbeigingisstillelusive.First,westreamlinedtheisolationprocessforpurifyinghighqualityadiposestemcellsthatareabletodifferentiateintowhiteorbeigeadipocytesfromdifferentspeciessuchashuman,pigormice.Next,weestablishedacold-inductionprocedureintransgenicmiceover-expressingAdipoR1andappliedalive3-D[18F]fluorodeoxyglucose-PET/CT(18F-FDGPET/CT)scanningtomeasureBATactivitybydeterminingglucoseuptakeincold-acclimatedtransgenicmice.Resultsshowedthatcold-acclimatedmiceover-expressingAdipoR1haddiminishedcold-inducedglucoseuptake,enlargedadipocytesizeinBATandinbrownedWAT,andreducedsurfaceBAT/bodytemperatureinvivo.Furthermore,decreasedgeneexpressionrelatedtothermogenicUcp1,BAT-specificmarkers,BAT-enrichedmitochondrialmarkers,lipolysisandfattyacidoxidationandincreasedexpressionofwhiteninggenesinBATorinbrownedsubcutaneousinguinalWATofAdipoR1micearecongruentwithresultsofPET/CTscanningandsurfacebodytemperatureinvivo.Moreover,differentiatedbrown-likebeigeadipocytesisolatedfrompre-adipocytesinsubcutaneousWAToftransgenicAdipoR1micealsohadsimilareffectsofloweredexpressionofthermogenicUcp1,BATselectivemarkers,andBATmitochondrialmarkers.Therefore,thisstudycombinesinvitroandinvivoresultswithlive3-Dscanningandrevealsoneofthemanyfacetsoftheadiponectinreceptorsinregulatingenergyhomeostasis,especiallyintheinvolvementofcold-inducedthermogenesis. 致謝ii中文摘要ivAbstractviTableofcontentsviiiListoffiguresxiListoftablesxiiiChapter1Literaturereview1Obesity-associatedinflammation3N-3PUFAandtheiranti-inflammatoryeffects5N-3PUFAsuppresscytokine-inducedinflammationtoreduceobesity-relatedresponses.8GPR120mediatestheanti-inflammatoryandinsulin-sensitizingactionsofDHA9InvolvementofFoxOininflammatoryresponses11Processeselevatingclassicalbrownadiposeorbeigingofwhiteadiposetissueactivity15OrchestrationofadiposeinflammationandthermogenesisinBAT/whiteadiposebrowning16Alternativeactivatedmacrophages(AAM)onbrowningofwhiteadiposetissues17RoleofFoxOinclassicalbrownandbeigeadipogenesis18PUFAonbrowning/beigingofwhiteadipocytes24Futureperspective27Chapter2SpecificAim29Chapter3OverexpressionofAdiponectinReceptor1InhibitsBrownandBeigeAdiposeTissueActivityinMice30Introduction30MaterialsandMethods34Animalsanddiets34Cold-acclimationprocedure35Samplecollectionandpreparation36PET/CTscanning36HistologicalanalysisbyH&Estain37Depotsurfacetemperaturemeasurementsandthermographicimaging37GeneexpressionanalysisbyqPCR38Cellcultureforisolationanddifferentiationofmousestromal/vascularcellsintomatureadipocytes39Statisticalanalysis40Results43Enhancedbody-weightlossesinAdipoR1miceduringcoldexposure44Diminishedcold-inducedglucoseuptakebyPET/CTscanninginclassicalBATandbrownedsupWATofAdipoR1mice46EnlargedadipocytesizeinclassicalBATandbrownediWATofAdipoR1mice48Decreasedsurfacedepottemperatureandsurfacebodytemperatureincold-inducedAdipoR1mice50Increasedadiposeexpressionofadiponectin,adiponectinreceptors,andbrownadipocytemarkersinWTfemalemiceversusWTmalemiceundercoldexposure52ReducedadiponectinandadiponectinreceptorsinadiposetissuesofAdipoR1femalemiceversusWTfemalemiceundercoldexposure56Decreasedbrown-adipocyteselectivemarkersinclassicalBATandbrownediWATofAdipoR1femalemiceundercoldexposure58Decreasedexpressionofglucoseuptake,lipolysis,andfattyacidoxidationgenesinclassicalBATandbrownediWATofAdipoR1miceundercoldexposure61DecreasedexpressionofbrowninggenesandenhancedwhiteninggenesinclassicalBATandbrownediWATofAdipoR1miceaftercoldexposure64DecreasedbrownadipocytesmarkersindifferentiatedbeigeadipocytesisolatedfromiWATofAdipoR1mice67Discussion70PET/CTandcold-inducedglucoseuptake70BATandcold-inducedglucoseuptake73Adiponectin/AdipoR1onmodulatingBATandbrownedWAT74Conclusion80Chapter4Isolationanddifferentiationofadipose-derivedstemcellsfromporcinesubcutaneousadiposetissues81Introduction81Materialsandequipment83Protocol85Representativeresults100Discussion106References110AppendixI141Publicationlist141AppendixII143CurriculumVitae143 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