scholarly journals Mechanism of Action of a Peroxisome Proliferator-Activated Receptor (PPAR)-δ Agonist on Lipoprotein Metabolism in Dyslipidemic Subjects with Central Obesity

2011 ◽  
Vol 96 (10) ◽  
pp. E1568-E1576 ◽  
Author(s):  
Esther M. M. Ooi ◽  
Gerald F. Watts ◽  
Dennis L. Sprecher ◽  
Dick C. Chan ◽  
P. Hugh R. Barrett
Keyword(s):  
High Density Lipoprotein ◽  
Central Obesity ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Peroxisome Proliferator ◽  
Low Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Plasma Triglycerides

Abstract Context: Dyslipidemia increases the risk of cardiovascular disease in obesity. Peroxisome proliferator-activated receptor (PPAR)-δ agonists decrease plasma triglycerides and increase high-density lipoprotein (HDL)-cholesterol in humans. Objective: The aim of the study was to examine the effect of GW501516, a PPAR-δ agonist, on lipoprotein metabolism. Design, Setting, and Intervention: We conducted a randomized, double-blind, crossover trial of 6-wk intervention periods with placebo or GW501516 (2.5 mg/d), with 2-wk placebo washout between treatment periods. Participants: We recruited 13 dyslipidemic men with central obesity from the general community. Main Outcome Measures: We measured the kinetics of very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein-, and low-density lipoprotein (LDL)-apolipoprotein (apo) B-100, plasma apoC-III, and high-density lipoprotein (HDL) particles (LpA-I and LpA-I:A-II). Results: GW501516 decreased plasma triglycerides, fatty acid, apoB-100, and apoB-48 concentrations. GW501516 decreased the concentrations of VLDL-apoB by increasing its fractional catabolism and of apoC-III by decreasing its production rate (P < 0.05). GW501516 reduced VLDL-to-LDL conversion and LDL-apoB production. GW501516 increased HDL-cholesterol, apoA-II, and LpA-I:A-II concentrations by increasing apoA-II and LpA-I:A-II production (P < 0.05). GW501516 decreased cholesteryl ester transfer protein activity, and this was paralleled by falls in the triglyceride content of VLDL, LDL, and HDL and the cholesterol content of VLDL and LDL. Conclusions: GW501516 increased the hepatic removal of VLDL particles, which might have resulted from decreased apoC-III concentration. GW501516 increased apoA-II production, resulting in an increased concentration of LpA-I:A-II particles. This study elucidates the mechanism of action of this PPAR-δ agonist on lipoprotein metabolism and supports its potential use in treating dyslipidemia in obesity.

The effects of hormone implants on serum lipoproteins and steroid hormones in bilaterally oophorectomised women

1984 ◽  
Vol 106 (1) ◽  
pp. 116-120 ◽  
Author(s):  
E. Farish ◽  
C. D. Fletcher ◽  
D. M. Hart ◽  
F. Al. Azzawi ◽  
H. I. Abdalla ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Serum Lipoproteins ◽  
Cholesterol Levels ◽  
Transient Rise

Abstract. Serum lipoproteins were measured over a period of 6 months in 14 oophorectomised women treated with oestrogen implants (50 mg oestradiol-17β) and 17 oophorectomised women treated with oestrogen/testosterone implants (50 mg oestradiol-17β, 100 mg testosterone). Both types of implant caused only minimal changes in lipoprotein metabolism. Low density lipoprotein (LDL) cholesterol decreased with both types of implant and high density lipoprotein (HDL) cholesterol rose with the oestrogen implants. HDL subfractions were also measured. The oestrogen implants caused a transient rise in HDL2 cholesterol levels at 2 months and a slower rise in HDL3 cholesterol. The oestrogen/testosterone implants had no effect on HDL fractions. The results indicate that hormone implants do not cause the profound changes in lipoproteins associated with oral hormone therapy.

scholarly journals Unique Mode of Lipogenic Activation in Rat Preputial Sebocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Dianne Deplewski ◽  
Kenan Qin ◽  
Nancy Ciletti ◽  
Robert L. Rosenfield
Keyword(s):  
Fatty Acids ◽  
High Density Lipoprotein ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Peroxisome Proliferator ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipogenic Genes ◽  
Ppar Agonists

Lipoprotein delivery of fatty acids and cholesterol is linked with peroxisome proliferator-activated receptor (PPAR) activation in adipocytes and macrophages. We postulated that similar interactions exist in sebaceous epithelial cells (sebocytes) in which PPAR activation induces differentiation. High-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) markedly enhanced sebocyte differentiation above that found with PPAR agonists and were more potent than explicable by their lipid content. The PPARγantagonist GW5393 reduced sebocyte differentiation to all PPAR isoform agonists, HDL and VLDL, suggesting that the lipoprotein effect on differentiation occurs partially through activation of PPARγ. Furthermore, we found that sebocytes expressed a unique pattern of lipogenic genes. Our results demonstrate that HDL and VLDL are the most potent inducers of sebocyte differentiation tested to date, and these actions are partially inhibited by PPAR antagonists. This suggests that substrates provided by lipoproteins are targeted to sebocytes and affect their own disposition via PPAR activation.

Oxidized low-density lipoprotein and peroxisome-proliferator-activated receptor α down-regulate platelet-activating-factor receptor expression in human macrophages

2001 ◽  
Vol 354 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Delphine HOURTON ◽  
Philippe DELERIVE ◽  
Jana STANKOVA ◽  
Bart STAELS ◽  
M. John CHAPMAN ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Platelet Activating Factor ◽  
Density Lipoprotein ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Low Density ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Mrna ◽  
Paf Receptor ◽  
Pparα Agonist

Regulation of the expression of platelet-activating factor (PAF) receptor by atherogenic lipoproteins might contribute to atherogenesis. We show that progressive oxidation of low-density lipoprotein (LDL) gradually inhibits PAF receptor expression on the macrophage cell surface. We tested the effect of oxidized LDL (oxLDL) on PAF receptor expression in human monocytes that do not contain peroxisome-proliferator-activated receptor γ (PPARγ), a nuclear receptor activated by oxLDL. OxLDL decreased by 50% (P ⩽0.001) and by 29% (P⩽0.05) the binding of PAF and the expression of PAF receptor mRNA respectively. Next we demonstrated that progressive oxidation of LDLs significantly activated PPARα-dependent transcription in transfected mouse aortic endothelial cells. Finally we demonstrated, in mature macrophages, that fenofibrate (20µM), a specific PPARα agonist, but not the specific PPARγ agonist BRL49653 (20nM), significantly decreased both PAF binding and PAF receptor mRNA expression, by 65% and 40% (P⩽0.001) respectively. Additionally, another PPARα agonist, Wy14,643, decreased PAF receptor promoter activity by 70% (P⩽0.05) in transfected THP-1 cells, suggesting the involvement of the proximal promoter region (-980 to -500) containing a series of four nuclear factor (NF)-κB motifs. Thus PPARα might be involved in the down-regulation of PAF receptor gene expression by oxLDLs in human monocytes/macrophages. The oxidation of one or more lipid components of LDLs might result in the formation of natural activators of PPARα. It is hypothesized that such activators might modulate inflammation and apoptosis upon atherogenesis by decreasing the expression of PAF receptor.

scholarly journals PEMANFAATA N EKSTRAK DAUN WUNGU {Graptophyllum pictum (L.) Griff.} UNTUK PENURUNAN KADAR KOLESTEROL SERUM DARAH MENCIT BETINA YANG DIOVARIEKTOMI

2008 ◽  
Vol 13 (2) ◽  
pp. 97-100
Author(s):  
Listijani Suhargo
Keyword(s):  
High Density Lipoprotein ◽  
Fish Oil ◽  
Blood Serum ◽  
High Density Lipoprotein Cholesterol ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Low Density ◽  
Ovariectomized Mice

The purpose of this research was conducted to evaluate the effects of daun wungu extracts to decrease total cholesterol, LDL (Low Density Lipoprotein) and HDL (High Density Lipoprotein) cholesterol of ovariectomized mice. This research used 24 ovariectomized mice and 8 normal mice. The ovariectomized mice were grouped in 3 groups for K1 (the treatment with aquadest, 0.05 ml), K2 (the treatment with fish oil, 0.05 ml) and P (the treatment with daun wungu extracts, 0.5 mg in 0.05 ml fish oil). All treatments were done for 20 days. At the end of the treatments, the blood (0.5 ml) was taken from cardiac by tuberculin disposable syringe. And then with fotometry, serum total, LDL and HDL cholesterol were measured. The result of this research showed that daun wungu extracts (0.5 mg in 0.05 ml fish oil) could not decrease HDL cholesterol, but it could decrease total and LDL cholesterol of blood serum in ovariectomized mice.

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