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Investigating the Effects of Stearoyl-CoA Desaturase on Diet-Induced Adiposity and the Regulation of Insulin-Like Growth Factor-Binding Protein 1- [electronic resource]
Investigating the Effects of Stearoyl-CoA Desaturase on Diet-Induced Adiposity and the Reg...
Investigating the Effects of Stearoyl-CoA Desaturase on Diet-Induced Adiposity and the Regulation of Insulin-Like Growth Factor-Binding Protein 1- [electronic resource]

Detailed Information

자료유형  
 학위논문파일 국외
최종처리일시  
20240214095841
ISBN  
9798379695392
DDC  
574
저자명  
O'Neill, Lucas M. .
서명/저자  
Investigating the Effects of Stearoyl-CoA Desaturase on Diet-Induced Adiposity and the Regulation of Insulin-Like Growth Factor-Binding Protein 1 - [electronic resource]
발행사항  
[S.l.]: : The University of Wisconsin - Madison., 2021
발행사항  
Ann Arbor : : ProQuest Dissertations & Theses,, 2021
형태사항  
1 online resource(189 p.)
주기사항  
Source: Dissertations Abstracts International, Volume: 84-12, Section: B.
주기사항  
Advisor: Ntambi, James.
학위논문주기  
Thesis (Ph.D.)--The University of Wisconsin - Madison, 2021.
사용제한주기  
This item must not be sold to any third party vendors.
사용제한주기  
This item must not be added to any third party search indexes.
초록/해제  
요약Currently, obesity remains a worldwide epidemic and increases the risk of comorbidities such as type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease, and cancer. Therefore, comprehensive investigations into the biochemical pathways that promote obesity continue to be warranted. One biochemical pathway of interest is the de novo biosynthesis of monounsaturated fatty acids, which is catalyzed by the stearoyl-CoA desaturase family of enzymes. There are four SCD isoforms in mice (SCD1-4) and two in humans (hSCD1 & hSCD5). In mice, global deletion of Scd1 (GKO) conveys protection against both high-fat diet (HFD) and high-carbohydrate diet (HCD) -induced obesity. Furthermore, deletion of Scd1 in the skin (SKO) and liver (LKO) recapitulated protection against HFD and HCD, respectively. GKO and SKO mice are protected against HFD because they are hypermetabolic due to a defective skin barrier that leads to a breakdown in adaptive thermoregulation. The mechanism of HCD protection in LKO mice is currently unclear but evidence suggests it involves multiple hepatokines. One hepatokine of interest is insulin-like growth factor-binding protein-1 (IGFBP1). IGFBP1 is one of the most differentially expressed genes between GKO and wild-type mice and enhanced IGFBP1 expression has been reported to promote glucose uptake and insulin sensitivity. To date, the relationship between Scd1 deficiency and up-regulation of IGFBP1 has not been established and it is unknown if global deletion of other SCD isoforms will yield similar protection against diet-induced adiposity. In this dissertation, I examine the metabolic effects of the SCD2 isoform under HFD and HCD diet feeding conditions, the role of SCD2 in preadipocyte differentiation in vivo and in vitro, and the relationship between hepatic SCD1 and IGFBP1. Specifically, I show that: 1. Global deletion of Scd2 conveys protection against diet-induced adiposity and improves glucose and insulin tolerance; 2. SCD2 is not required for preadipocyte differentiation in vivo despite being required in vitro; and 3. Hepatic oleic acid levels regulate insulin-like growth factor-binding protein 1 partially through the mTOR-FGF21 axis during high-carbohydrate feeding.
일반주제명  
Biochemistry.
일반주제명  
Public health.
일반주제명  
Epidemiology.
키워드  
Obesity
키워드  
Fatty acids
키워드  
Biochemical pathway
키워드  
Hepatic oleic acid
키워드  
Liver disease
키워드  
Cancer
기타저자  
The University of Wisconsin - Madison Biochemistry-ALS
기본자료저록  
Dissertations Abstracts International. 84-12B.
기본자료저록  
Dissertation Abstract International
전자적 위치 및 접속  
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MARC

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■00520240214095841
■006m          o    d                
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■020    ▼a9798379695392
■035    ▼a(MiAaPQ)AAI28496796
■040    ▼aMiAaPQ▼cMiAaPQ
■0820  ▼a574
■1001  ▼aO'Neill,  Lucas  M.  .
■24510▼aInvestigating  the  Effects  of  Stearoyl-CoA  Desaturase  on  Diet-Induced  Adiposity  and  the  Regulation  of  Insulin-Like  Growth  Factor-Binding  Protein  1▼h[electronic  resource]
■260    ▼a[S.l.]:▼bThe  University  of  Wisconsin  -  Madison.  ▼c2021
■260  1▼aAnn  Arbor  :▼bProQuest  Dissertations  &  Theses,  ▼c2021
■300    ▼a1  online  resource(189  p.)
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  84-12,  Section:  B.
■500    ▼aAdvisor:  Ntambi,  James.
■5021  ▼aThesis  (Ph.D.)--The  University  of  Wisconsin  -  Madison,  2021.
■506    ▼aThis  item  must  not  be  sold  to  any  third  party  vendors.
■506    ▼aThis  item  must  not  be  added  to  any  third  party  search  indexes.
■520    ▼aCurrently,  obesity  remains  a  worldwide  epidemic  and  increases  the  risk  of  comorbidities  such  as  type  2  diabetes,  non-alcoholic  fatty  liver  disease,  cardiovascular  disease,  and  cancer.  Therefore,  comprehensive  investigations  into  the  biochemical  pathways  that  promote  obesity  continue  to  be  warranted.  One  biochemical  pathway  of  interest  is  the  de  novo  biosynthesis  of  monounsaturated  fatty  acids,  which  is  catalyzed  by  the  stearoyl-CoA  desaturase  family  of  enzymes.  There  are  four  SCD  isoforms  in  mice  (SCD1-4)  and  two  in  humans  (hSCD1  &  hSCD5).  In  mice,  global  deletion  of  Scd1  (GKO)  conveys  protection  against  both  high-fat  diet  (HFD)  and  high-carbohydrate  diet  (HCD)  -induced  obesity.  Furthermore,  deletion  of  Scd1  in  the  skin  (SKO)  and  liver  (LKO)  recapitulated  protection  against  HFD  and  HCD,  respectively.  GKO  and  SKO  mice  are  protected  against  HFD  because  they  are  hypermetabolic  due  to  a  defective  skin  barrier  that  leads  to  a  breakdown  in  adaptive  thermoregulation.  The  mechanism  of  HCD  protection  in  LKO  mice  is  currently  unclear  but  evidence  suggests  it  involves  multiple  hepatokines.  One  hepatokine  of  interest  is  insulin-like  growth  factor-binding  protein-1  (IGFBP1).  IGFBP1  is  one  of  the  most  differentially  expressed  genes  between  GKO  and  wild-type  mice  and  enhanced  IGFBP1  expression  has  been  reported  to  promote  glucose  uptake  and  insulin  sensitivity.  To  date,  the  relationship  between  Scd1  deficiency  and  up-regulation  of  IGFBP1  has  not  been  established  and  it  is  unknown  if  global  deletion  of  other  SCD  isoforms  will  yield  similar  protection  against  diet-induced  adiposity.  In  this  dissertation,  I  examine  the  metabolic  effects  of  the  SCD2  isoform  under  HFD  and  HCD  diet  feeding  conditions,  the  role  of  SCD2  in  preadipocyte  differentiation  in  vivo  and  in  vitro,  and  the  relationship  between  hepatic  SCD1  and  IGFBP1.  Specifically,  I  show  that:  1.  Global  deletion  of  Scd2  conveys  protection  against  diet-induced  adiposity  and  improves  glucose  and  insulin  tolerance;  2.  SCD2  is  not  required  for  preadipocyte  differentiation  in  vivo  despite  being  required  in  vitro;  and  3.  Hepatic  oleic  acid  levels  regulate  insulin-like  growth  factor-binding  protein  1  partially  through  the  mTOR-FGF21  axis  during  high-carbohydrate  feeding.
■590    ▼aSchool  code:  0262.
■650  4▼aBiochemistry.
■650  4▼aPublic  health.
■650  4▼aEpidemiology.
■653    ▼aObesity
■653    ▼aFatty  acids
■653    ▼aBiochemical  pathway
■653    ▼aHepatic  oleic  acid
■653    ▼aLiver  disease
■653    ▼aCancer
■690    ▼a0487
■690    ▼a0766
■690    ▼a0573
■71020▼aThe  University  of  Wisconsin  -  Madison▼bBiochemistry-ALS.
■7730  ▼tDissertations  Abstracts  International▼g84-12B.
■773    ▼tDissertation  Abstract  International
■790    ▼a0262
■791    ▼aPh.D.
■792    ▼a2021
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16930946▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.
■980    ▼a202402▼f2024

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