The effect of Bariatric surgery on VLDL metabolism

Dyslipidemia, which is characterized by elevated triglyceride rich lipoprotein levels in plasma, is a major health risk associated with obesity and insulin resistance. Increased hepatic very low density lipoprotein (VLDL) secretion and/or its decreased clearance from circulation is a key characteristic of dyslipidemia. Bariatric surgery is performed on morbidly obese patients to induce weight loss and improve health. After the surgery, several ameliorations are observed in these patients, including, weight loss, improved dyslipidemia and insulin sensitivity. Enhanced VLDL metabolism after the surgery is one of the key contributors of improved dyslipidemia. Therefore, the impact of bariatric surgery on VLDL metabolism is of great interest.
Studies show that VLDL metabolism is regulated by insulin and interaction between VLDL and other lipoprotein species starts in the liver and continues in the plasma, through exchange of material and competition for the same clearance pathways. The complexity induced by these regulatory mechanisms, interactions and feedbacks make computational models very effective at exploring VLDL metabolism. In this project, we employ a computational model to analyze stable isotopic tracer data collected from morbidly obese patients that went Roux en-Y gastric bypass surgery (RYGB). We investigate the effects of RYGB on VLDL metabolism by examining the evolution of physiological parameters after the surgery. We explore the role that insulin plays in VLDL metabolism and the effects of surgery on insulin dependent regulation. By performing a sensitivity analysis, we identify the relative contribution of each component to the overall improvement and pinpoint the key factors.