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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]

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.