dc.contributor.advisor | Pua, Heather H | |
dc.creator | Sprenkle, Neil T | |
dc.date.accessioned | 2024-01-29T19:00:40Z | |
dc.date.available | 2024-01-29T19:00:40Z | |
dc.date.created | 2023-12 | |
dc.date.issued | 2023-09-22 | |
dc.date.submitted | December 2023 | |
dc.identifier.uri | http://hdl.handle.net/1803/18596 | |
dc.description.abstract | Identifying molecular circuits that control adipose tissue macrophage (ATM) function is necessary to understand how ATMs contribute to tissue homeostasis and obesity-induced insulin resistance. In this study, we found that mice with a myeloid-specific knockout of the miR-23-27-24 clusters of miRNAs gained less weight on a high-fat diet but exhibited worsened glucose and insulin tolerance. Analysis of ATMs from these mice revealed selectively reduced numbers and proliferation of a recently reported subset of lipid-associated CD9+Trem2+ ATMs (LAMs). Leveraging the role of miRNAs to control networks of genes, we used RNA sequencing, functional screens, and biochemical assays to identify candidate target transcripts that regulate proliferation-associated signaling. We determined that Eif4ebp2 is a direct target of miR-23, which we found to inhibit protein synthesis and proliferation in macrophages. Altogether, our study demonstrates that control of proliferation of a protective subset of LAMs by noncoding RNAs contributes to protection against diet-induced obesity metabolic dysfunction. | |
dc.format.mimetype | application/pdf | |
dc.language.iso | en | |
dc.subject | Lipid-Associated Macrophages, MicroRNAs, Obesity, Proliferation | |
dc.title | The miR-23-27-24 Clusters Drive Lipid-Associated Macrophage Proliferation in Obese Adipose Tissue | |
dc.type | Thesis | |
dc.date.updated | 2024-01-29T19:00:40Z | |
dc.type.material | text | |
thesis.degree.name | PhD | |
thesis.degree.level | Doctoral | |
thesis.degree.discipline | Molecular Pathology Immunology | |
thesis.degree.grantor | Vanderbilt University Graduate School | |
dc.creator.orcid | 0000-0003-2999-4929 | |
dc.contributor.committeeChair | Serezani, C. Henrique | |