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

Diabetes Care ◽  
2021 ◽  
Vol 44 (4) ◽  
pp. 1027-1037
Author(s):  
Bruno Vergès ◽  
Laurence Duvillard ◽  
Jean Paul Pais de Barros ◽  
Benjamin Bouillet ◽  
Sabine Baillot-Rudoni ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Proprotein Convertase ◽  
Apolipoprotein B100

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

2021 ◽  
Author(s):  
Bruno Vergès ◽  
Laurence Duvillard ◽  
Jean Paul Pais de Barros ◽  
Benjamin Bouillet ◽  
Sabine Baillot-Rudoni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Receptor Protein ◽  
Proprotein Convertase ◽  
Positive Effects ◽  
Ldl Particles ◽  
Expression Of Genes ◽  
Apolipoprotein B100

<a><b>OBJECTIVE:</b></a> Dyslipidemia observed in type 2 diabetes (T2DM) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles which, all have apolipoprotein B100 (apoB100) as major apolipoprotein. This prompted us to study the effect of the GLP1 agonist, liraglutide, on the metabolism of apoB100 containing lipoproteins. <p><b>RESEARCH DESIGN AND METHODS</b>: We performed an <i>in vivo</i> kinetic study with stable isotopes (L-[1-<sup>13</sup>C] leucine) in 10 T2DM patients before and after 6-month treatment with liraglutide (1.2 mg/day). We also evaluated, in mice, the effect of liraglutide on the expression of genes involved in apoB100 containing lipoprotein clearance.</p> <p><b>RESULTS</b>: In T2DM patients, liraglutide treatment significantly reduced plasma apoB100 (0.93±0.13 vs. 1.09±0.11 g/L, p=0.011) and fasting triglycerides (1.76±0.37 vs. 2.48±0.69 mmol/L, p=0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL<sub>1</sub>-apoB100 (4.11±1.91 vs. 2.96±1.61 day<sup>-1</sup>,p=0.005), VLDL<sub>2</sub>-apoB100 (5.17±2.53 vs. 2.84±1.65 day<sup>-1</sup>,p=0.008), IDL-apoB100 (5.27±2.77 vs. 3.74±1.85 day<sup>-1</sup>,p=0.017) and in catabolism of LDL-apoB100 (0.72±0.22 vs. 0.56±0.22 day<sup>-1</sup>,p=0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced Proprotein convertase subtilisin/kexin type 9 (PCSK9), Retinol Binding Protein 4 (RBP4) and Tumor Necrosis Factor alpha (TNF alpha) gene expression in adipose tissue, and decreased PCSK9 mRNA and increased LDL-receptor protein expression, in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver.</p> <p><b>CONCLUSIONS</b>: Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL<sub>1</sub>, VLDL<sub>2</sub>, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100 containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2DM.</p>

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

2021 ◽  
Author(s):  
Bruno Vergès ◽  
Laurence Duvillard ◽  
Jean Paul Pais de Barros ◽  
Benjamin Bouillet ◽  
Sabine Baillot-Rudoni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Receptor Protein ◽  
Proprotein Convertase ◽  
Positive Effects ◽  
Ldl Particles ◽  
Expression Of Genes ◽  
Apolipoprotein B100

<a><b>OBJECTIVE:</b></a> Dyslipidemia observed in type 2 diabetes (T2DM) is atherogenic. Important features of diabetic dyslipidemia are increased levels of triglyceride-rich lipoproteins and small dense LDL particles which, all have apolipoprotein B100 (apoB100) as major apolipoprotein. This prompted us to study the effect of the GLP1 agonist, liraglutide, on the metabolism of apoB100 containing lipoproteins. <p><b>RESEARCH DESIGN AND METHODS</b>: We performed an <i>in vivo</i> kinetic study with stable isotopes (L-[1-<sup>13</sup>C] leucine) in 10 T2DM patients before and after 6-month treatment with liraglutide (1.2 mg/day). We also evaluated, in mice, the effect of liraglutide on the expression of genes involved in apoB100 containing lipoprotein clearance.</p> <p><b>RESULTS</b>: In T2DM patients, liraglutide treatment significantly reduced plasma apoB100 (0.93±0.13 vs. 1.09±0.11 g/L, p=0.011) and fasting triglycerides (1.76±0.37 vs. 2.48±0.69 mmol/L, p=0.005). The kinetic study showed a significant increase in indirect catabolism of VLDL<sub>1</sub>-apoB100 (4.11±1.91 vs. 2.96±1.61 day<sup>-1</sup>,p=0.005), VLDL<sub>2</sub>-apoB100 (5.17±2.53 vs. 2.84±1.65 day<sup>-1</sup>,p=0.008), IDL-apoB100 (5.27±2.77 vs. 3.74±1.85 day<sup>-1</sup>,p=0.017) and in catabolism of LDL-apoB100 (0.72±0.22 vs. 0.56±0.22 day<sup>-1</sup>,p=0.005). In mice, liraglutide increased lipoprotein lipase (LPL) gene expression and reduced Proprotein convertase subtilisin/kexin type 9 (PCSK9), Retinol Binding Protein 4 (RBP4) and Tumor Necrosis Factor alpha (TNF alpha) gene expression in adipose tissue, and decreased PCSK9 mRNA and increased LDL-receptor protein expression, in liver. In vitro, liraglutide directly reduced the expression of PCSK9 in the liver.</p> <p><b>CONCLUSIONS</b>: Treatment with liraglutide induces a significant acceleration of the catabolism of triglyceride-rich lipoproteins (VLDL<sub>1</sub>, VLDL<sub>2</sub>, IDL) and LDL. Liraglutide modifies the expression of genes involved in apoB100 containing lipoprotein catabolism. These positive effects on lipoprotein metabolism may reduce cardiovascular risk in T2DM.</p>

Effect of Atorvastatin on Apolipoprotein B100 Containing Lipoprotein Metabolism in Type-2 Diabetes

2003 ◽  
Vol 306 (1) ◽  
pp. 332-337 ◽  
Author(s):  
Khadija Ouguerram ◽  
Thierry Magot ◽  
Yassine Zäir ◽  
J. S. Marchini ◽  
Bernard Charbonnel ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lipoprotein Metabolism ◽  
Apolipoprotein B100
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