Jayela Davis: Validating Bilirubin and Vitamin D Combination to Alleviate Cholesterol Levels

Obese and overweight individuals tend to have lower levels of bilirubin and vitamin D3 (VitD3) and higher adiposity and plasma cholesterol levels which are both risk factors for cardiovascular disease. Within the cell, bilirubin and VitD3 bind to nuclear receptors, PPARa and vitamin D receptor (VDR), respectively. We have previously identified that bilirubin reduces adiposity and plasma cholesterol in vivo and lowers lipid accumulation in vitro. In our preliminary studies using 3T3-L1 differentiated adipocytes, we found that the cotreatment of bilirubin and VitD3 significantly decreased the amount of lipid accumulation compared to bilirubin alone. However, whether lower levels of bilirubin and VitD3 impact the metabolic status and how these molecules function together are currently unknown. We hypothesized that they have crosstalk in their signaling pathways and, together, are stronger at reducing adiposity and lowering the risk for cardiovascular disease. This work aims to determine whether there is a synergism between bilirubin and VitD3 that might further reduce adiposity and cholesterol levels. For our studies, we will use AC16 human ventricle cardiomyocytes, murine AML12 hepatocytes, and murine 3T3-L1 differentiated adipocytes treated with bilirubin and VitD3 or a combination to determine how these affect lipid accumulation and pathways that mediate cholesterol levels such as the sterol regulatory-element binding protein (SREBP). We will use cell differentiation, CRISPR knockout technology, cell staining, and real-time polymerase chain reaction to complete the studies. We will compare the effects of bilirubin and VitD3 with atorvastatin, a cholesterol lowering medication that activates the SREBP pathway to increase the uptake of cellular cholesterol, as this is the current standard of care for hypercholesterolemia. This is the first study to investigate the synergistic effects of bilirubin and VitD3 and will determine the therapeutic significance for the use of bilirubin and VitD3 for treating obesity and hypercholesterolemia to lower the risk of cardiovascular disease.