scholarly journals Effects of Atorvastatin on the Clearance of Triglyceride-Rich Lipoproteins in Familial Combined Hyperlipidemia

2004 ◽  
Vol 89 (12) ◽  
pp. 5972-5980 ◽  
Author(s):  
M. Castro Cabezas ◽  
C. Verseyden ◽  
S. Meijssen ◽  
H. Jansen ◽  
D. W. Erkelens
Keyword(s):  
Low Density Lipoprotein ◽  
Postprandial Lipemia ◽  
Density Lipoprotein ◽  
Familial Combined Hyperlipidemia ◽  
Atorvastatin Treatment ◽  
Fasting Plasma ◽  
Postprandial Triglyceride ◽  
Before And After ◽  
Apolipoprotein B48 ◽  
Loading Tests

Abstract Familial combined hyperlipidemia (FCHL) patients have an impaired catabolism of postprandial triglyceride (TG)-rich lipoproteins (TRLs). We investigated whether atorvastatin corrects the delayed clearance of large TRLs in FCHL by evaluating the acute clearance of Intralipid (10%) and TRLs after oral fat-loading tests. Sixteen matched controls were included. Atorvastatin reduced fasting plasma TG (from 3.6 ± 0.4 to 2.5 ± 0.3 mm; mean ± sem) without major effects on fasting apolipoprotein B48 (apoB48) and apoB100 in large TRLs. Atorvastatin significantly reduced fasting intermediate density lipoprotein (Svedberg flotation, 12–20)-apoB100 concentrations. After Intralipid, TG in plasma and TRL showed similar kinetics in FCHL before and after atorvastatin treatment, although compared with controls, the clearance of large TRLs was only significantly slower in untreated FCHL, suggesting an improvement by atorvastatin. Investigated with oral fat-loading tests, the clearance of very low density lipoprotein (Sf20–60)-apoB100 improved by 24%, without major changes in the other fractions. The most striking effects of atorvastatin on postprandial lipemia in FCHL were on hepatic TRL, without major improvements on intestinal TRLs. Fasting plasma TG should be reduced more aggressively in FCHL to overcome the lipolytic disturbance causing delayed clearance of postprandial TRLs.

Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects

1995 ◽  
Vol 268 (4) ◽  
pp. E588-E594 ◽  
Author(s):  
J. L. Potts ◽  
S. W. Coppack ◽  
R. M. Fisher ◽  
S. M. Humphreys ◽  
G. F. Gibbons ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Postprandial Lipemia ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Control Group ◽  
Postprandial Period ◽  
Before And After ◽  
Obese Subjects ◽  
Subcutaneous Adipose

Adipose tissue is an important site of clearance of circulating triacylglycerol (TAG), especially in the postprandial period. Postprandial lipemia is usually increased in obesity. We studied the extraction of TAG from plasma and TAG-rich lipoproteins (TRLs) in subcutaneous adipose tissue in 11 control and 8 obese subjects before and after a mixed meal. Clearance of plasma TAG and very low-density lipoprotein (VLDL)-TAG was decreased in the obese subjects after an overnight fast. After the meal, chylomicron-TAG extraction increased in the control group whereas VLDL-TAG clearance decreased; these changes were not seen in the obese group, in whom the VLDL particles appeared to be better able to compete with the chylomicrons for clearance by lipoprotein lipase. In the control subjects, removal of TAG from the TRL in the postprandial period was accompanied by a shift toward addition of cholesterol to the high-density lipoprotein (HDL) fraction; this was not observed in the obese subjects. We conclude that disturbed TRL-TAG clearance in adipose tissue is related both to the elevated plasma TAG concentrations and the depressed HDL-cholesterol concentrations typical of obesity.

scholarly journals Relationship of Zonulin with Serum PCSK9 Levels after a High Fat Load in a Population of Obese Subjects

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 748
Author(s):  
María Molina-Vega ◽  
Daniel Castellano-Castillo ◽  
Lidia Sánchez-Alcoholado ◽  
Isaac Plaza-Andrade ◽  
Gabriel Perera-Martin ◽  
...  
Keyword(s):  
Morbid Obesity ◽  
Intestinal Permeability ◽  
Low Density Lipoprotein ◽  
Linear Regression Analysis ◽  
Postprandial Lipemia ◽  
Density Lipoprotein ◽  
Significant Rise ◽  
Apolipoprotein A1 ◽  
High Fat ◽  
Before And After

Despite the fact that circulating levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) remain unchanged after fat load in healthy lean individuals, PCSK9 has been suggested to have a role in postprandial lipemia regulation in obese individuals. On the other hand, intestinal permeability and endotoxemia have been observed to increase more in obese individuals than in non-obese individuals after a lipid load. This study aimed to analyze the relationship between PCSK9, intestinal permeability, and endotoxemia after a high fat load in obese individuals. We included 39 individuals with morbid obesity. Serum PCSK9 levels, intestinal permeability marker (zonulin), endotoxemia markers (LPS and LBP), and lipid parameters were measured before and after 3 h of fat load. A significant rise in triglycerides, apolipoprotein A1, zonulin, LPS, and LBP, and a significant decline in PCSK9, were observed after a lipid load. Linear regression analysis showed that low-density lipoprotein cholesterol (LDL-C) was independently related to PCSK9 at baseline, whereas both zonulin and LDL-C were independently related to PCSK9 levels after fat load. A relationship between zonulin and PCSK9 levels after fat load in individuals with morbid obesity may exist.

scholarly journals Anagliptin monotherapy in patients with type 2 diabetes mellitus and high low-density lipoprotein cholesterol reduces fasting plasma lathosterol level: a single-arm intervention trial

2020 ◽  
Author(s):  
Yuichi Ikegami ◽  
Ikuo Inoue ◽  
Yasuhiro Takenaka ◽  
Daigo Saito ◽  
Mitsuhiko Noda ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Fasting Plasma ◽  
Before And After

Background. Anagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels in plasma. Aim of study. The objective of our study is to elucidate the mechanisms responsible for anagliptin-mediated improvements in high LDL-C levels (hyper-LDL-C-emia). Methods. We prospectively examined the effects of anagliptin monotherapy on fasting plasma lathosterol, sitosterol, and campesterol levels in patients with type 2 diabetes mellitus and hyper-LDL-C-emia for 6 months. We examined 8 patients who did not use hypoglycemic or lipid-lowering drugs, other than anagliptin, for 4 months before initiating the study. Serum variables related to glucose and lipid metabolism were measured before and after the treatment for 6 months and pre- and post-prandially using the cookie-loading test. Results. After treatment, anagliptin monotherapy (n = 8) significantly decreased fasting LDL-C (182.8 to 167.8 mg/dL, as mean values of before and after the treatment) and plasma lathosterol levels (3.2 to 2.6 mg/dL); however, no significant changes were observed in fasting sitosterol or campesterol levels. Furthermore, a significant increase (p = 0.0012) in the change in 1-h post-prandial active glucagon-like peptide-1 (GLP-1) levels was observed after anagliptin treatment. For all participants (n = 17), fasting plasma lathosterol levels were negatively correlated with pre-prandial GLP-1 levels. Conclusion. Anagliptin monotherapy may have a beneficial effect on lipid metabolism, which is mediated by the inhibition of hepatic cholesterol synthesis, and not by the inhibition of intestinal lipid transport.

Melatonin Improves Lipid Profile and Ameliorates Lipid Peroxidation in Patients with Chronic Kidney Disease.

2018 ◽  
pp. 38-45
Keyword(s):  
Lipid Peroxidation ◽  
Placebo Group ◽  
Lipid Profile ◽  
Kidney Diseases ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Before And After ◽  
Inhibit Lipid Peroxidation ◽  
Controlled Clinical Study

Dyslipidemia and oxidative modifications of lipid are frequently associated in patients with chronic kidney diseases (CKD) and considered the most important risk factors for cardiovascular events. Melatonin is a well-known potent antioxidant and has beneficial effect on lipid metabolism. the study was designed to evaluate if Melatonin could improve lipid profile and ameliorates lipid peroxidation. This single blind placebo controlled clinical study carried out on 41 patients with CKD who were randomized into two groups, control groups (n=20) those who received placebo cap and melatonin group those who received 5mg melatonin (n=21). Lipid profile [total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C)] and parameters of lipid peroxidation [oxidized LDL (oxLDL) and malondialdehyde (MDA) were measured before and after 12 weeks of the treatment. After 12 weeks of treatment, melatonin significantly increased HDL-C and decreased LDL-C compared to the initial value. The elevation in HDL-C and reduction in LDL-C were significantly different from that in placebo group. Also, both oxLDL and MDA levels significantly lowered by melatonin compared to the baseline and to the placebo group. Collectively, the results of our study showed that melatonin has advantageous effect on lipid profile and inhibit lipid peroxidation in patients with CKD.

Therapeutic Application of Diacylglycerol Oil for Obesity: Serotonin Hypothesis

2012 ◽  
Vol 2 (1) ◽  
pp. 1 ◽  
Author(s):  
Hidekatsu Yanai ◽  
Hiroshi Yoshida ◽  
Yuji Hirowatari ◽  
Norio Tada
Keyword(s):  
Energy Expenditure ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Serotonin Release ◽  
Intestinal Cell ◽  
Therapeutic Application ◽  
Postprandial Triglyceride

Characteristics for the serum lipid abnormalities in the obesity/metabolic syndrome are elevated fasting, postprandial triglyceride (TG), and decreased high-density lipoprotein-cholesterol (HDL-C). Diacylglycerol (DAG) oil ingestion has been reported to ameliorate postprandial hyperlipidemia and prevent obesity by increasing energy expenditure, due to the intestinal physiochemical dynamics that differ from triacylglycerol (TAG). Our study demonstrated that DAG suppresses postprandial increase in TG-rich lipoprotein, very low-density lipoprotein (VLDL), and insulin, as compared with TAG in young, healthy individuals. Interestingly, our study also presented that DAG significantly increases plasma serotonin, which is mostly present in the intestine, and mediates thermogenesis, proposing a possible mechanism for a postprandial increase in energy expenditure by DAG. Our other study demonstrated that DAG suppresses postprandial increase in TG, VLDL-C, and remnant-like particle-cholesterol, in comparison with TAG in an apolipoprotein C-II deficient subject, suggesting that DAG suppresses postprandial TG-rich lipoprotein independently of lipoprotein lipase. Further, to understand the molecular mechanisms for DAG-mediated increase in serotonin and energy expenditure, we studied the effects of 1-monoacylglycerol and 2-monoacylglycerol, distinct digestive products of DAG and TAG, respectively, on serotonin release from the Caco-2 cells, the human intestinal cell line. We also studied effects of 1- and 2-monoacylglycerol, and serotonin on the expression of mRNA associated with β-oxidation, fatty acids metabolism, and thermogenesis, in the Caco-2 cells. 1-monoacylglycerol significantly increased serotonin release from the Caco-2 cells, compared with 2-monoacylglycerol by approximately 40%. The expression of mRNA of acyl-CoA oxidase (ACO), fatty acid translocase (FAT), and uncoupling protein-2 (UCP-2), was significantly higher in 1-MOG-treated Caco-2 cells, than 2-MOG-treated cells. The expression of mRNA of ACO, medium-chain acyl-CoA dehydrogenase, FAT, and UCP-2, was significantly elevated in serotonin-treated Caco-2 cells, compared to cells incubated without serotonin. In conclusion, our clinical and in vitro studies suggested a possible therapeutic application of DAG for obesity, and obesity-related metabolic disorders.Key words: Diacylglycerol, intestine, obesity, serotonin, thermogenesis

scholarly journals Genetic variation of RNF145 gene and blood lipid levels in Xinjiang population, China

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jing Ming ◽  
Xian Wei ◽  
Min Han ◽  
Dilare Adi ◽  
Jialin Abuzhalihan ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Ring Finger ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Lipid Profiles ◽  
Cholesterol Levels ◽  
General Linear Model Analysis ◽  
Confounding Variables ◽  
Before And After ◽  
Detection Response

AbstractDyslipidemia is one of the main risk factors for coronary heart disease (CHD). The E3 ubiquitin ligase which is encoded by the ring finger protein 145 (RNF145) gene is very important in the mediation of cholesterol synthesis and effectively treats hypercholesterolemia. Thus, the purpose of the present research is to investigate the connection between the polymorphism of the RNF145 gene and cholesterol levels in the populations in Xinjiang, China. A total of 1396 participants (Male: 628, Female: 768) were included in this study for genetic analysis of RNF145 gene, and we used the modified multiple connection detection response (iMLDR) technology to label two SNPs (rs17056583, rs12188266) of RNF145 genotyping. The relationship between the genotypes and the lipid profiles was analyzed with general linear model analysis after adjusting confounding variables. Through the analysis of the two SNPs in RNF145 gene, we discovered that both rs17056583 and rs12188266 were related to total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (All P < 0.001). In addition, the association of rs17056583 and rs12188266 with lipid profiles concentrations is still statistically significant after multivariate adjustment of sex, age, smoking, obesity, drinking, diabetes, hypertension and lipid profiles. Meanwhile, we also found that rs17056583 was associated with high triglycerides concentrations before and after adjustment (All P < 0.001). Our study shows that both rs17056583 and rs12188266 SNPs of RNP145 gene are related to TC and LDL-C concentrations in Xinjiang population.

scholarly journals Treatment with Delipid Extracorporeal Lipoprotein Filter from Plasma after Intravenous Thrombolysis for Acute Ischemic Stroke: A Single-Center Experience

2020 ◽  
Vol 10 (3) ◽  
pp. 148-158
Author(s):  
Yu Cui ◽  
Zhong-He Zhou ◽  
Xiao-Wen Hou ◽  
Hui-Sheng Chen
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Intravenous Thrombolysis ◽  
Single Center Experience ◽  
Before And After ◽  
Prospective Trials ◽  
Symptomatic Intracranial Hemorrhage ◽  
Rate Of Improvement

<b><i>Introduction:</i></b> The delipid extracorporeal lipoprotein filter from plasma (DELP) has been approved for the treatment of acute ischemic stroke (AIS) by the China Food and Drug Administration, but its effectiveness and mechanism are not yet fully determined. The purpose of this study was to evaluate the effect of DELP treatment on AIS patients after intravenous thrombolysis. <b><i>Methods:</i></b> A retrospective study was performed on AIS patients with no improvement within 24 h after intravenous thrombolysis who were subsequently treated with or without DELP. Primary outcome was the proportion with a modified Rankin scale (mRS) of 0–1 at 90 days. Secondary outcomes were changes in National Institute of Health Stroke Scale (NIHSS) score from 24 h to 14 days after thrombolysis, and the rate of improvement in stroke-associated pneumonia (SAP). The main safety outcomes were the rates of symptomatic intracranial hemorrhage and mortality. To investigate its mechanisms, serum biomarkers were measured before and after DELP. <b><i>Results:</i></b> A total of 252 patients were recruited, 63 in the DELP group and 189 matched patients in the NO DELP group. Compared with the NO DELP group, the DELP group showed an increase in the proportion of mRS 0–1 at 90 days (<i>p</i> = 0.042). More decrease in NIHSS from 24 h to 14 days (<i>p</i> = 0.024), a higher rate of improvement in SAP (<i>p</i> = 0.022), and lower mortality (<i>p</i> = 0.040) were shown in DELP group. Furthermore, DELP decreased levels of interleukin (IL)-1β, E-selectin, malondialdehyde, matrix metalloprotein 9, total cholesterol, low-density lipoprotein, and fibrinogen, and increased superoxide dismutase (<i>p</i>&#x3c; 0.05). <b><i>Conclusions:</i></b> DELP following intravenous thrombolysis should be safe, and is associated with neurological function improvement, possibly through multiple neuroprotective mechanisms. Prospective trials are needed.

Drug related metabolites and genetic polymorphisms predict low low-density lipoprotein cholesterol response to atorvastatin treatment in patients with coronary heart disease

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Munkhaugen ◽  
E Sverre ◽  
O Kristiansen ◽  
M.W Fagerland ◽  
K Peersen ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Genetic Polymorphisms ◽  
Individual Variation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Funding Source ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Atorvastatin Treatment

Abstract Background There is considerable individual variation in the low-density lipoprotein cholesterol (LDL-C) reduction at all classes and doses of statins. Knowledge of the determinants of individual variation LDL-C response upon statin treatment may pave the way for personalized and optimized statin treatment. Purpose We aimed to determine clinical and drug related predictors of variability of LDL-C response to atorvastatin 40 mg in patients with coronary heart disease. Methods This is an explorative study among 70 patients enrolled in the MUscle Side-Effects of atorvastatin in coronary patients (MUSE) randomized double blinded cross-over trial. Absolute and relative changes in LDL-C after 7 weeks treatment with atorvastatin 40 mg/day and 7 weeks treatment with placebo, were calculated for each patient. Linear regression analyses were applied to investigate the association between clinical (10 variables) and drug related (atorvastatin and/or metabolites, 18 variables) predictors and changes in LDL-C. Results Adherence to allocated treatment was high as confirmed by atorvastatin levels in blood and a mean proportion of days covered of 99% (range 91–100%). Mean reduction in LDL-C on atorvastatin treatment (LDL-C atorvastatin – LDL-C placebo) was 2.1 (SD 0.7, range 0.3 to 3.4) mmol/L. Mean percentage reduction in LDL-C was 51.1 (SD 11.2, range 29 to 60)%, and 37 patients (52.9%) had &lt;50% LDL-C reduction. Genetic polymorphisms in SLCO1B1 or CYP3A (B 0.06, 95% CI 0.01 to 0.12, p=0.026), increasing number of coronary events (B 0.06, 95% CI 0.002 to 0.10, p=0.005), increasing trough concentration of 4-OH atorvastatin lactone (B 0.05, 95% CI 0.01 to 0.08, p=0.005) and increasing trough concentration of 4-OH atorvastatin acid (B 0.05, 95% CI 0.01 to 0.08, p=0.006) were the significant determinants of lower relative change (%) in LDL-C, in adjusted analyses. Age, gender, somatic comorbidity, cardiovascular risk factors, statin dependent muscle side-effects and other clinical and drug related determinants were not associated with changes in LDL-C. Conclusions There is considerable inter-individual variation in the LDL-C response upon treatment with atorvastatin despite confirmed high statin adherence. This is the first study reporting that genetic polymorphisms involved in the metabolism of statins and atorvastatin metabolites predict lower LDL-C response. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Association of Health, Grant/Award

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