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

Abstract

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.