scholarly journals Lipoprotein Lipase Inhibitor, Nordihydroguaiaretic Acid, Aggravates Metabolic Phenotypes and Alters HDL Particle Size in the Western Diet-Fed db/db Mice

2019 ◽  
Vol 20 (12) ◽  
pp. 3057 ◽  
Author(s):  
Inhae Kang ◽  
Miyoung Park ◽  
Soo Jin Yang ◽  
Myoungsook Lee
Keyword(s):  
Particle Size ◽  
Lipoprotein Lipase ◽  
Leptin Receptor ◽  
Density Lipoprotein ◽  
Nordihydroguaiaretic Acid ◽  
Western Diet ◽  
Knock Out ◽  
Metabolic Phenotypes ◽  
Stress Signals ◽  
Lpl Mass

Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoprotein to supply fatty acids, and its deficiency leads to hypertriglyceridemia, thereby inducing metabolic syndrome (MetSyn). Nordihydroguaiaretic acid (NDGA) has been recently reported to inhibit LPL secretion by endoplasmic reticulum (ER)-Golgi redistribution. However, the role of NDGA on dyslipidemia and MetSyn remains unclear. To address this question, leptin receptor knock out (KO)-db/db mice were randomly assigned to three different groups: A normal AIN76-A diet (CON), a Western diet (WD) and a Western diet with 0.1% NDGA and an LPL inhibitor, (WD+NDGA). All mice were fed for 12 weeks. The LPL inhibition by NDGA was confirmed by measuring the systemic LPL mass and adipose LPL gene expression. We investigated whether the LPL inhibition by NDGA alters the metabolic phenotypes. NDGA led to hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. More strikingly, the supplementation of NDGA increased the percentage of high density lipoprotein (HDL)small (HDL3a+3b+3c) and decreased the percentage of HDLlarge (HDL2a+2b) compared to the WD group, which indicates that LPL inhibition modulates HDL subclasses. was NDGA increased adipose inflammation but had no impact on hepatic stress signals. Taken together, these findings demonstrated that LPL inhibition by NDGA aggravates metabolic parameters and alters HDL particle size.

Abstract 577: MicroRNA-30c Reduces Plasma Cholesterol in Different Hypercholesterolemic and Hyperglycemic Mouse Models

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Sara Irani ◽  
Jahangir Iqbal ◽  
M.Mahmood Hussain
Keyword(s):  
Mouse Models ◽  
Metabolic Disorders ◽  
Leptin Receptor ◽  
Plasma Lipids ◽  
Plasma Cholesterol ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
High Plasma ◽  
Western Diet ◽  
Lower Plasma

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein assembly and secretion; however, this is associated with steatosis. We have shown that microRNA-30c (miR-30c) reduces Western diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe -/- mice with no obvious adverse effects by reducing hepatic lipoprotein production and lipid synthesis. Here, we tested the effect of miR-30c on plasma lipids, transaminases and hepatic lipids in five different mouse models. Hepatic delivery of miR-30c reduced MTP activity but did not affect plasma cholesterol, triglyceride and glucose in chow-fed C57Bl6J and streptozotocin-induced diabetic, normolipidemic mice. However, hepatic delivery of miR-30c to chow fed leptin deficient ( ob/ob ) and leptin receptor deficient ( db/db ) hypercholesterolemic and hyperglycemic type 2 diabetic mice reduced cholesterol in total plasma and VLDL/LDL by ~ 28%and ~ 25%, respectively, without affecting phospholipid, triglyceride and glucose levels. Interestingly, these mice had lower plasma transaminases and creatine kinases indicating possible beneficial effects. Mechanistic studies showed that miR-30c reduced hepatic MTP activity and lipid synthesis. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western-diet fed low density lipoprotein receptor knockout mice with no effect on plasma triglyceride, glucose and transaminases, suggesting that miR-30c can be a potential therapeutic agent for homozygous familial hypercholesterolemia. In all these studies, hepatic lipid levels were similar in control and miR-30c injected mice. These studies indicate that miR-30c reduces plasma cholesterol in diet-induced and diabetic hyperholesterolemic mice but not in normocholesterolemic mice. Thus, miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.

scholarly journals Free cholesterol transfer to high-density lipoprotein (HDL) upon triglyceride lipolysis underlies the U-shape relationship between HDL-cholesterol and cardiovascular disease

2019 ◽  
Vol 27 (15) ◽  
pp. 1606-1616 ◽  
Author(s):  
Ma Feng ◽  
Maryam Darabi ◽  
Emilie Tubeuf ◽  
Aurélie Canicio ◽  
Marie Lhomme ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
High Density Lipoprotein ◽  
Lipoprotein Lipase ◽  
Free Cholesterol ◽  
Density Lipoprotein ◽  
High Density ◽  
Knock Out ◽  
Low Hdl

Background Low concentrations of high-density lipoprotein cholesterol (HDL-C) represent a well-established cardiovascular risk factor. Paradoxically, extremely high HDL-C levels are equally associated with elevated cardiovascular risk, resulting in the U-shape relationship of HDL-C with cardiovascular disease. Mechanisms underlying this association are presently unknown. We hypothesised that the capacity of high-density lipoprotein (HDL) to acquire free cholesterol upon triglyceride-rich lipoprotein (TGRL) lipolysis by lipoprotein lipase underlies the non-linear relationship between HDL-C and cardiovascular risk. Methods To assess our hypothesis, we developed a novel assay to evaluate the capacity of HDL to acquire free cholesterol (as fluorescent TopFluor® cholesterol) from TGRL upon in vitro lipolysis by lipoprotein lipase. Results When the assay was applied to several populations markedly differing in plasma HDL-C levels, transfer of free cholesterol was significantly decreased in low HDL-C patients with acute myocardial infarction (−45%) and type 2 diabetes (–25%), and in subjects with extremely high HDL-C of >2.59 mmol/L (>100 mg/dL) (−20%) versus healthy normolipidaemic controls. When these data were combined and plotted against HDL-C concentrations, an inverse U-shape relationship was observed. Consistent with these findings, animal studies revealed that the capacity of HDL to acquire cholesterol upon lipolysis was reduced in low HDL-C apolipoprotein A-I knock-out mice and was negatively correlated with aortic accumulation of [3H]-cholesterol after oral gavage, attesting this functional characteristic as a negative metric of postprandial atherosclerosis. Conclusions Free cholesterol transfer to HDL upon TGRL lipolysis may underlie the U-shape relationship between HDL-C and cardiovascular disease, linking HDL-C to triglyceride metabolism and atherosclerosis.

Low density lipoprotein particle size and risk factors of insulin resistance syndrome

2000 ◽  
Vol 148 (1) ◽  
pp. 141-149 ◽  
Author(s):  
Yechiel Friedlander ◽  
Miriam Kidron ◽  
Muriel Caslake ◽  
Tracey Lamb ◽  
Michael McConnell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Particle Size ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Insulin Resistance Syndrome ◽  
Low Density ◽  
Lipoprotein Particle ◽  
Lipoprotein Particle Size
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