College of Health
27 Elucidating the Role of BMPER in Beige Adipocyte Development and Expansion
Elijah Liu
Faculty Mentor: Sihem Boudina (Nutrition and Integrative Physiology, University of Utah)
The leading cause of death in the United States is caused by cardiovascular disease, the two major contributors are obesity and metabolic syndrome. Brown and beige adipocytes can burn energy to produce heat (thermogenesis), becoming extensive targets for understanding how the body regulates metabolism and obesity intervention. Brown fat decreases with age, but beige adipocytes can be produced within white adipose tissue (WAT), making it a promising area for obesity research. BMP-binding Endothelial Regulator (BMPER), a protein involved in BMP signaling and angiogenesis has been recently identified in the Boudina lab as a potential regulator for adipocyte development. My project aims to understand whether BMPER is important for the formation and function of beige adipocytes.
To better elucidate BMPER’s role, I used a conditional knockout mouse model, isolating BMPER then removing it from Pdgfra+ adipose progenitor cells. Next I isolated stromal vascular fraction (SVF) cells from inguinal WAT (iWAT) and cultured them to differentiate either white or beige adipocytes in culture. During differentiation, I examined lipid accumulation, cell morphology, and gene expression. Subsequently I used qPCR to measure the levels of thermogenic genes like Ucp1 and Cidea, markers of beige adipocytes, as well as Cpt1b, a gene relating to mitochondrial metabolism.
The results revealed that BMPER knockout cells were still able to become adipocytes, indicating BMPER is not required for general adipogenesis. However, the knockout cells had a significant reduction in Ucp1 and Cidea expression compared to wild-type cells. This shows that BMPER plays a specific role for beige adipocytes along with its thermogenic function. Surprisingly, Cpt1b levels remained similar between groups, suggesting that although mitochondrial number might be unchanged, the mitochondrial function may be weakened without BMPER. Overall, these findings denote BMPER being a key regulator of beige adipogenesis and energy-burning capacity.
Another aspect of my project involved tracing BMPER-expressing cells during embryonic development. I used a tamoxifen-inducible lineage-tracing mouse model. Using tamoxifen-inducible BMPER reporter mice at embryonic day E10.5, we labeled BMPER+ cells in embryonic brown fat at E15.5. The beige adipocyte however only appeared after birth, and the labeling process failed due to oral gavage delivery of tamoxifen causing the pregnant mice to miscarry. Although this was a difficult obstacle, fixing this issue taught me how complex in-vivo experiments can be. After discussing with my mentor and other experts, we decided to switch the method of delivering tamoxifen to tip-feeding and intraperitoneal injection, reducing stress on the mothers and allowing us to collect the postnatal data needed.
Reflecting on this project, I obtained valuable skills in mouse handling, timed pregnancy, SCG isolation, adipocyte differentiation, qPCR and data interpretation. On top of that I learned how to problem-solve when experiments don’t go as planned and how to communicate effectively with my research team. This research has strengthened my interest in metabolic health and given me a deeper understanding of the biological factors involved in obesity. Overall, I’m very grateful to have this opportunity and very thankful for my mentor, graduate students and everyone that has supported me throughout this journey.
Bibliography
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Tiffany M. Powell-Wiley, Paul Poirier, Lora E. Burke, Jean-Pierre Després, Penny Gordon-Larsen, Carl J. Lavie, Scott A. Lear, Chiadi E. Ndumele, Ian J. Neeland, Prashanthan Sanders, Marie-Pierre St-Onge (2021, April 22). Obesity and Cardiovascular Disease: A Scientific Statement From the American Heart Association, https://www.ahajournals.org/doi/10.1161/CIR.0000000000000973
Wu, J., Boström, P., Sparks, L. M., Ye, L. & Hyun Choi, J. (2012). Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human, Cell, 150(2). https://doi.org/10.1016/j.cell.2012.05.016. https://www.sciencedirect.com/science/article/pii/S0092867412005958
