Identification of ITGBL1: A Novel Regulator of Adipogenesis
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Obesity is a global epidemic that increases the risk for chronic metabolic disease. Pathological expansion of white adipose tissue (WAT) leads to insulin resistance and cardiovascular disease. To date, the mechanisms driving the formation of new adipocytes in obesity remain unclear. We have identified a perivascular (mural) cell population that gives rise to new adipocytes in obese animals. These cells are defined by the expression of Zfp423, a transcription factor that drives the cell differentiation program. Using Zfp423-GFP reporter mice, we have isolated these adipocyte precursors and obtained global gene expression profiles. The most differentially regulated protein was ITGBL1, which was highly expressed in the Zfp423+ mural cells. Given its high expression in these primed early preadipocytes, we investigated the role of ITGBL1 in preadipocyte differentiation in vitro. Here, we show that shRNA or CRISPR-mediated inactivation of ITGBL1 expression increases the propensity of mesenchymal stem cells to undergo adipocyte differentiation. These data suggest that this previously uncharacterized protein serves as an inhibitor or "brake" on the adipocyte differentiation program in preadipocytes. Multiple analyses using available structures of homologous proteins show that Itgbl1 has high structural similarity to DLL1, a known Notch ligand. We show that inactivation of ITGBL1 expression decreases expression of key Notch target genes throughout adipogenesis, thus suggesting a role for ITGBL1 in the activation of Notch signaling (known to inhibit adipogenesis in mesenchymal stem cells in vitro). Ongoing efforts are focused on elucidating ITGBL1's mechanism of action and potential as a novel Notch ligand, as well as its physiological significance in vivo. These studies will lead to a better understanding of how adipose tissue expands in obesity, and how we might promote healthy adipose expansion, preventing insulin resistance and the onset of metabolic syndrome.
The 54th Annual Medical Student Research Forum at UT Southwestern Medical Center (Monday, January 19, 2016, 2-5 p.m., D1.700)
Each year the Medical Student Research Program awards students for the best oral presentation and the best poster presentation as judged by faculty across campus. This author received an award as one of the best oral presentations at this forum.
SubjectBasic Research and Disease Models
Best Oral Presentation Award
Spurgin, S. B., Vishvanath, L., MacPherson, K. A., Hepler, C., Shao. M., & Gupta R. K. (2016, January 19). Identification of ITGBL1: a novel regulator of adipogenesis. Poster presented at the 54th Annual Medical Student Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/3261