Liraglutide Increases the Catabolism of Apolipoprotein B100–Containing Lipoproteins in Patients With Type 2 Diabetes and Reduces Proprotein Convertase Subtilisin/Kexin Type 9 Expression

OBJECTIVE Dyslipidemia observed in type 2 diabetes (T2D) is atherogenic. Important features of diabetic dyslipidemia are increased levels triglyceride-rich lipoproteins and small dense LDL particles, which all have apolipoprotein B100 (apoB100) as a major apolipoprotein. This prompted us to study the effect GLP-1 agonist liraglutide on metabolism apoB100-containing lipoproteins. RESEARCH DESIGN AND METHODS We performed an vivo kinetic with stable isotopes (L-[1-13C]leucine) 10 patients T2D before after 6 months treatment (1.2 mg/day). also evaluated mice expression genes involved lipoprotein clearance. RESULTS In T2D, significantly reduced plasma apoB100 (0.93 ± 0.13 vs. 1.09 0.11 g/L, P = 0.011) fasting triglycerides (1.76 0.37 2.48 0.69 mmol/L, 0.005). The showed significant increase indirect catabolism VLDL1-apoB100 (4.11 1.91 2.96 1.61 pools/day, 0.005), VLDL2-apoB100 (5.17 2.53 2.84 1.65 0.008), IDL-apoB100 (5.27 2.77 3.74 1.85 0.017) LDL-apoB100 (0.72 0.22 0.56 mice, lipase (LPL) gene proprotein convertase subtilisin/kexin 9 (PCSK9), retinol-binding protein 4 (RBP4), tumor necrosis factor-? (TNF-?) adipose tissue decreased PCSK9 mRNA receptor liver. vitro, directly CONCLUSIONS Treatment induces acceleration (VLDL1, VLDL2, IDL) LDL. Liraglutide modifies catabolism. These positive effects may reduce cardiovascular risk T2D.