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

<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-[1-¹³C] 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 VLDL₁-apoB100 (4.11±1.91 vs. 2.96±1.61 day^-1,p=0.005), VLDL₂-apoB100 (5.17±2.53 vs. 2.84±1.65 day^-1,p=0.008), IDL-apoB100 (5.27±2.77 vs. 3.74±1.85 day^-1,p=0.017) and in catabolism of LDL-apoB100 (0.72±0.22 vs. 0.56±0.22 day^-1,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 (VLDL₁, VLDL₂, 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>

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

<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-[1-¹³C] 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 VLDL₁-apoB100 (4.11±1.91 vs. 2.96±1.61 day^-1,p=0.005), VLDL₂-apoB100 (5.17±2.53 vs. 2.84±1.65 day^-1,p=0.008), IDL-apoB100 (5.27±2.77 vs. 3.74±1.85 day^-1,p=0.017) and in catabolism of LDL-apoB100 (0.72±0.22 vs. 0.56±0.22 day^-1,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 (VLDL₁, VLDL₂, 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>

Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA

Background The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA. Methods Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure. Results Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period. Conclusion Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA. Trial registration This trial is registered at ClinicalTrials.gov as NCT02941055.

Gadofullerene inhibits the degradation of apolipoprotein B100 and boosts triglyceride transport for reversing hepatic steatosis

Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using β-alanine–modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid–induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.

Study of LCAT and some biochemical parameters in cardiovascular patient

The Clinical study included individuals (m23ales and females aged 25-75y) with cardiovascular disease. The activity of Lecithin: cholesterol acyl transferase (LCAT) and glutathione peroxidase(GPx) was estimated, in addition to the level of apolipoprotein AI (apo AI), apolipoprotein B100 (apoB100), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), glutathione (GSH), peroxy nitrate (PN), malondialdehyde (MDA), glucose and certain elements (Zn, Cu, Mg and Co) in blood serum. The results showed that there was a significant decrease in the activity of LCAT and GPx, and the level of apoAI, HDL-c, GSH, Zn and Mg. on the other hand, it was shown that there was a significant increase in the level of apoB100, TC, TG, LDL-c, PN, Glu, Cu and Co but on unsignificant change in the level of MDA for both male and females. http://dx.doi.org/10.25130/tjps.25.2020.026