Bariatric surgery improves postprandial VLDL kinetics and restores insulin-mediated regulation of hepatic VLDL production

Dyslipidemia in obesity results from excessive production and impaired clearance of triglyceride-rich (TG-rich) lipoproteins, which are particularly pronounced in the postprandial state. Here, we investigated the impact of Roux-en-Y gastric bypass (RYGB) surgery on postprandial VLDL(1) and VLDL(2) apoB and TG kinetics and their relationship with insulin-responsiveness indices. Morbidly obese patients without diabetes who were scheduled for RYGB surgery (n = 24) underwent a lipoprotein kinetics study during a mixed-meal test and a hyperinsulinemic-euglycemic clamp study before the surgery and 1 year later. A physiologically based computational model was developed to investigate the impact of RYGB surgery and plasma insulin on postprandial VLDL kinetics. After the surgery, VLDL(1) apoB and TG production rates were significantly decreased, whereas VLDL(2) apoB and TG production rates remained unchanged. The TG catabolic rate was increased in both VLDL(1) and VLDL(2) fractions, but only the VLDL(2) apoB catabolic rate tended to increase. Furthermore, postsurgery VLDL(1) apoB and TG production rates, but not those of VLDL(2), were positively correlated with insulin resistance. Insulin-mediated stimulation of peripheral lipoprotein lipolysis was also improved after the surgery. In summary, RYGB resulted in reduced hepatic VLDL(1) production that correlated with reduced insulin resistance, elevated VLDL(2) clearance, and improved insulin sensitivity in lipoprotein lipolysis pathways.