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

• Published in: JCI insight 2023-08, Vol.8 (16)
• Main Authors: Yildirim, Vehpi, Ter Horst, Kasper W, Gilijamse, Pim W, van Harskamp, Dewi, Schierbeek, Henk, Jansen, Hans, Schimmel, Alinda Wm, Nieuwdorp, Max, Groen, Albert K, Serlie, Mireille J, van Riel, Natal Aw, Dallinga-Thie, Geesje M
• Format: Article
• Language: English
• Subjects: Metabolism
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.166905

Dyslipidemia in obesity results from excessive production and impaired clearance of triglyceride (TG)-rich lipoproteins, which is particularly pronounced in the postprandial state. Here, we investigated the impact of Roux-en-Y gastric bypass (RYGB) surgery on the postprandial VLDL1 and VLDL2 apoB and TG kinetics and their relationship with insulin responsiveness indices. 24 obese non-diabetic RYGB surgery patients underwent a lipoprotein kinetics study during a mixed meal test and a hyperinsulinemic-euglycemic clamp study before the surgery, and one 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, VLDL1 apoB and TG production rates were significantly decreased, whereas VLDL2 apoB and TG production rates remained unchanged. TG catabolic rate was increased in both VLDL1 and VLDL2 fractions, but only the VLDL2 apoB catabolic rate tended to increase. Furthermore, post-surgery VLDL1 apoB and TG production rates, but not VLDL2, were positively correlated with insulin resistance. Insulin-mediated stimulation of peripheral lipoprotein lipolysis was also improved after the surgery. In summary, RYGB resulted in a reduced hepatic VLDL1 production that correlated with reduced insulin resistance, an elevated VLDL2 clearance, and improved insulin sensitivity in lipoprotein lipolysis pathways.