PhD Public Seminar - Noah Hahn
PhD Public Seminar - Noah Hahn
Defence date: Thursday, July 18th, 2024.
Time: 1:00 PM (Seminar)
Location: Multimedia Room, 3rd floor, PGCRL (686 Bay Street)
Title: Irx3 and Irx5 function in adipose tissue.
Abstract:
IRX3 and IRX5 (IRX3/5) are regulators of obesity in humans. The tissue, cell types and mechanisms that confers their metabolic activity is contested. In this thesis, I document Irx3/5’s functions in adipose tissue. Irx3/5 are expressed in adipocyte precursors and their expression is attenuated during adipocyte differentiation. I showed that in 3T3-L1 preadipocytes, a model of in vitro adipocyte differentiation, Irx3/5 are required for adipogenesis. On the other hand, in mice, Irx3/5 is dispensable for adipogenesis but are thought to control adipose beiging. Using an adipocyte precursor cell-specific gene dosage reduction of Irx3/5, Sim1-Cre;Irx3flIrx5eGFP/+ mice, I demonstrated adipose-autonomous suppression of beiging by Irx3/5. Sim1-Cre;Irx3flIrx5eGFP/+ mice exhibit leanness and adipose beiging. The beige adipocytes that arise from anterior subcutaneous white adipose tissue of Sim1-Cre;Irx3flIrx5eGFP/+ exhibited characteristics of glycolytic beige adipocytes. To grasp the molecular functions of Irx3/5 in adipose, I generated epitope-tagged mouse alleles for use in biochemical analyses. I used these mice for affinity purification combined with mass spectrometry techniques to investigate their protein-protein interaction partners in E10.5 embryos. I generated a high quality list of candidate interactions, and validated the interactions with ATF2 and CSKN2B. This work advances our understanding of Irx3/5’s functions in adipose tissue and provides novel tools to investigate their molecular interactions.
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