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Characterizing Alternative Splicing in Adipose Tissue Function and Metabolic Disease
Characterizing Alternative Splicing in Adipose Tissue Function and Metabolic Disease
상세정보
- 자료유형
- 학위논문 서양
- 최종처리일시
- 20250211150927
- ISBN
- 9798381945218
- DDC
- 575
- 서명/저자
- Characterizing Alternative Splicing in Adipose Tissue Function and Metabolic Disease
- 발행사항
- [Sl] : The University of Chicago, 2024
- 발행사항
- Ann Arbor : ProQuest Dissertations & Theses, 2024
- 형태사항
- 115 p
- 주기사항
- Source: Dissertations Abstracts International, Volume: 85-09, Section: B.
- 주기사항
- Advisor: Nobrega, Marcelo.
- 학위논문주기
- Thesis (Ph.D.)--The University of Chicago, 2024.
- 초록/해제
- 요약Obesity is a complex disease, with both environmental and genetic causes, and it confers a significant global health burden while remaining difficult to treat and prevent. A better understanding of the risk factors that lead to disease and the underlying regulatory responses of specific disease states can provide insight into possible new treatments and interventions to improve health outcomes worldwide. Here, I provide insight into both environmental and genetic causes for obesity through two parallel studies. First, I investigate one of the main environmental factors leading to obesity: diet. In particular, I dissect the impact of differences in dietary macronutrient composition on metabolic measures and gene regulation in adipose tissue, measuring both gene expression and splicing changes. I identify thousands of genes and exons that are responsive to dietary macronutrient composition in adipose tissue, and link them to specific macronutrient patterns and cellular functions. One particularly strong gene regulatory response is the differential expression of genes associated with Bardet-Biedl syndrome in response to dietary fat content. In my second study, I expand our understanding of the contribution of genetics to obesity through assaying alternative splicing across the differentiation of preadipocytes isolated from lean, obese, and obese with type 2 diabetes (T2D) individuals. I find that splicing is highly dynamic across adipocyte differentiation and is impacted by metabolic phenotype. I also find that there is significant enrichment for an overlap between regions that are differentially spliced across adipocyte differentiation and variants that are associated with T2D. In both studies, I find that there is very little overlap between genes that are differentially expressed in response to the perturbation of interest and those that are differentially spliced. These results suggest that alternative splicing and expression may represent largely separate modes of gene regulation, and that studies that seek to describe gene regulatory responses to stimuli should strive to measure alternative splicing in addition to gene expression to capture a more complete picture of the gene regulatory change. Overall, these studies provide insight into adipose tissue function and both environmental and genetic risk for obesity, and can serve as a resource to guide future variant-to-function studies.
- 일반주제명
- Genetics
- 일반주제명
- Physiology
- 일반주제명
- Biochemistry
- 일반주제명
- Nutrition
- 키워드
- Gene regulation
- 키워드
- Gene expression
- 키워드
- Obesity
- 키워드
- Type 2 diabetes
- 키워드
- Adipose tissue
- 기타저자
- The University of Chicago Human Genetics
- 기본자료저록
- Dissertations Abstracts International. 85-09B.
- 전자적 위치 및 접속
- 로그인 후 원문을 볼 수 있습니다.
MARC
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■00520250211150927
■006m o d
■007cr#unu||||||||
■020 ▼a9798381945218
■035 ▼a(MiAaPQ)AAI30989144
■040 ▼aMiAaPQ▼cMiAaPQ
■0820 ▼a575
■1001 ▼aFarris, Kathryn Marie.▼0(orcid)0000-0002-7599-8050
■24510▼aCharacterizing Alternative Splicing in Adipose Tissue Function and Metabolic Disease
■260 ▼a[Sl]▼bThe University of Chicago▼c2024
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2024
■300 ▼a115 p
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-09, Section: B.
■500 ▼aAdvisor: Nobrega, Marcelo.
■5021 ▼aThesis (Ph.D.)--The University of Chicago, 2024.
■520 ▼aObesity is a complex disease, with both environmental and genetic causes, and it confers a significant global health burden while remaining difficult to treat and prevent. A better understanding of the risk factors that lead to disease and the underlying regulatory responses of specific disease states can provide insight into possible new treatments and interventions to improve health outcomes worldwide. Here, I provide insight into both environmental and genetic causes for obesity through two parallel studies. First, I investigate one of the main environmental factors leading to obesity: diet. In particular, I dissect the impact of differences in dietary macronutrient composition on metabolic measures and gene regulation in adipose tissue, measuring both gene expression and splicing changes. I identify thousands of genes and exons that are responsive to dietary macronutrient composition in adipose tissue, and link them to specific macronutrient patterns and cellular functions. One particularly strong gene regulatory response is the differential expression of genes associated with Bardet-Biedl syndrome in response to dietary fat content. In my second study, I expand our understanding of the contribution of genetics to obesity through assaying alternative splicing across the differentiation of preadipocytes isolated from lean, obese, and obese with type 2 diabetes (T2D) individuals. I find that splicing is highly dynamic across adipocyte differentiation and is impacted by metabolic phenotype. I also find that there is significant enrichment for an overlap between regions that are differentially spliced across adipocyte differentiation and variants that are associated with T2D. In both studies, I find that there is very little overlap between genes that are differentially expressed in response to the perturbation of interest and those that are differentially spliced. These results suggest that alternative splicing and expression may represent largely separate modes of gene regulation, and that studies that seek to describe gene regulatory responses to stimuli should strive to measure alternative splicing in addition to gene expression to capture a more complete picture of the gene regulatory change. Overall, these studies provide insight into adipose tissue function and both environmental and genetic risk for obesity, and can serve as a resource to guide future variant-to-function studies.
■590 ▼aSchool code: 0330.
■650 4▼aGenetics
■650 4▼aPhysiology
■650 4▼aBiochemistry
■650 4▼aNutrition
■653 ▼aGene regulation
■653 ▼aGene expression
■653 ▼aMacronutrient composition
■653 ▼aObesity
■653 ▼aType 2 diabetes
■653 ▼aAdipose tissue
■690 ▼a0369
■690 ▼a0487
■690 ▼a0570
■690 ▼a0719
■71020▼aThe University of Chicago▼bHuman Genetics.
■7730 ▼tDissertations Abstracts International▼g85-09B.
■790 ▼a0330
■791 ▼aPh.D.
■792 ▼a2024
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17160179▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
