@article{Characterizing:11338,
      recid = {11338},
      author = {Farris, Kathryn Marie},
      title = {Characterizing Alternative Splicing in Adipose Tissue  Function and Metabolic Disease},
      publisher = {The University of Chicago},
      school = {Ph.D.},
      address = {2024-03},
      pages = {114},
      abstract = {Obesity 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. },
      url = {http://knowledge.uchicago.edu/record/11338},
      doi = {https://doi.org/10.6082/uchicago.11338},
}