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CHROMATIN ACCESSIBILITY CHANGES IN ADIPOSE TISSUE CONTRIBUTING TO THE METABOLIC BENEFITS OF BARIATRIC SURGERY

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dc.contributor.authorHarlan, Blaine
dc.contributor.chairSoloway, Paul
dc.contributor.committeeMemberDanko, Charles G.
dc.contributor.committeeMemberCummings, Bethany P.
dc.contributor.committeeMemberRoberson, Mark Stephen
dc.date.accessioned2022-01-24T18:08:16Z
dc.date.available2022-01-24T18:08:16Z
dc.date.issued2021-12
dc.description114 pages
dc.description.abstractMany adverse health outcomes result from dysregulation of cellular processes such as cell-cell signaling, transcription, protein modifications, and cellular metabolism. This includes obesity, leading to detrimental health outcomes involving type 2 diabetes and cardiometabolic disease. Vertical sleeve gastrectomy (VSG), a surgical obesity treatment, results in long-term weight loss and remission of type 2 diabetes in most patients. Some effects of VSG are independent of body weight, and the mechanisms behind the metabolic benefits are not fully understood. I performed single-nucleus ATAC-seq on adipose tissues from a VSG mouse model to reveal the mechanisms regulating adipose tissue and its contribution to the VSG-induced metabolic improvements. We observed depot-specific cellular composition and chromatin accessibility patterns altered by VSG. In particular, VSG reduced the accessibility of Scd1, which encodes a fatty acid desaturase. Additionally, SCD1-produced monounsaturated fatty acids were less abundant, meaning SCD1 activity was reduced. Obesity and insulin resistance are positively correlated with SCD1 activity, suggesting that the VSG-induced reduction in accessibility and activity of SCD1 acts as a metabolic switch in adipocytes, potentially leading to whole-body insulin sensitivity. These findings provide insights into how alterations to adipose lipid metabolism could contribute to the beneficial effects of VSG.
dc.identifier.doihttps://doi.org/10.7298/54pa-pt53
dc.identifier.otherHarlan_cornellgrad_0058F_12786
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:12786
dc.identifier.urihttps://hdl.handle.net/1813/110903
dc.language.isoen
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAdipocyte
dc.subjectAdipose
dc.subjectATAC-seq
dc.subjectSCD1
dc.subjectSingle-cell sequencing
dc.subjectVertical Sleeve Gastrectomy
dc.titleCHROMATIN ACCESSIBILITY CHANGES IN ADIPOSE TISSUE CONTRIBUTING TO THE METABOLIC BENEFITS OF BARIATRIC SURGERY
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810.2
thesis.degree.disciplineGenetics, Genomics and Development
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Genetics, Genomics and Development

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