Abstract 129: Liver-Specific and Intestine-Specific ACAT2 Knockout Mice Are Equally Protected from Diet-Induced Hepatic Cholesterol Accumulation

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Jun Zhang ◽  
Kathryn Kelley ◽  
Stephanie Marshall ◽  
Matthew Davis ◽  
Martha Wilson ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Absorption ◽  
Cholesterol Homeostasis ◽  
Cholesterol Accumulation ◽  
Very Low Density Lipoproteins ◽  
Plasma Triglycerides ◽  
Hepatic Lipid Accumulation ◽  
Vldl Cholesterol

Acyl-CoA:cholesterol acyltransferase 2 (ACAT2) is exclusively expressed in the small intestine and liver. ACAT2 facilitates the movement of cholesterol among tissues by generating cholesteryl ester (CE) for packaging into newly synthesized chylomicrons and very low-density lipoproteins (VLDL). In these studies we investigated whether CE derived from either the intestine or liver would differentially affect hepatic and plasma cholesterol homeostasis. For this purpose, we generated both liver-specific (ACAT2L-/L-) and intestine-specific (ACAT2SI-/SI-) ACAT2 knockout mice, and studied dietary cholesterol-induced hepatic lipid accumulation and hypercholesterolemia. Interestingly, diet-induced accumulation of hepatic CE was similarly decreased in both ACAT2L-/L- and ACAT2SI-/SI- mice, and free cholesterol did not build up in the liver. Compared with control mice, both ACAT2L-/L- and ACAT2SI-/SI- mice had lower levels of plasma VLDL-cholesterol but higher plasma triglycerides. ACAT2SI-/SI- but not ACAT2L-/L- mice had blunted cholesterol absorption. Collectively, both ACAT2L-/L- and ACAT2SI-/SI- mice were equally protected from diet-induced hepatic CE accumulation and hypercholesterolemia. These results suggest that inhibition of either intestinal or hepatic ACAT2 improves atherogenic hyperlipidemia and limits hepatic CE accumulation in mice, indicating that inhibition of ACAT2 expression in either tissue likely would be beneficial for atheroprotection.

scholarly journals Hypertriglyceridemia and Lower LDL Cholesterol Concentration in Relation to Apolipoprotein E Phenotypes in Myotonic Dystrophy

1989 ◽  
Vol 16 (1) ◽  
pp. 129-133 ◽  
Author(s):  
Sital Moorjani ◽  
Daniel Gaudet ◽  
Claude Laberge ◽  
Marie Christine Thibault ◽  
Jean Mathieu ◽  
...  
Keyword(s):  
Myotonic Dystrophy ◽  
Ldl Cholesterol ◽  
Plasma Cholesterol ◽  
Plasma Lipid ◽  
Cholesterol Concentration ◽  
Plasma Triglycerides ◽  
Ldl Particles ◽  
Vldl Cholesterol ◽  
Apo E

ABSTRACT:Plasma lipid, lipoprotein levels and apolipoprotein apo E phenotypes were determined in 70 patients with myotonic dystrophy (MyD) and 81 controls. Marked differences were noticed in the apo E phenotype frequencies between the two groups. Plasma triglycerides and VLDL cholesterol were higher in MyD than controls, but only the latter was related to differences in the apo E phenotypes between two groups. Accordingly, the ratio of VLDL cholesterol/plasma triglycerides was increased significantly in MyD, suggesting accumulation of intermediary density particles due to lower affinity of E2 containing lipoproteins for lipoprotein cell receptors. The LDL cholesterol concentration was lower in MyD than controls and was related to differences in the apo E phenotype frequencies between the two groups. These results indicate increased removal of LDL particles in the apo E2 phenotypes, perhaps due to upregulation of LDL (B, E) receptor activity. Plasma cholesterol and HDL cholesterol concentrations were similar in both groups. Another feature of the study was lower levels of plasma cholesterol, triglycerides, VLDL and LDL cholesterol in the homozygous E4:E4 phenotype. These results suggest increased clearance rate of both VLDL and LDL particles and support the concept that apo E4-containing lipoproteins have higher in vivo affinity for ape E and/or B, E receptors.

scholarly journals Dietary Cholesterol Contained in Whole Eggs Is Not Well Absorbed and Does Not Acutely Affect Plasma Total Cholesterol Concentration in Men and Women: Results from 2 Randomized Controlled Crossover Studies

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1272 ◽  
Author(s):  
Jung Kim ◽  
Wayne Campbell
Keyword(s):  
Total Cholesterol ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Absorption ◽  
Blood Cholesterol ◽  
Cholesterol Concentration ◽  
Total Cholesterol Concentration ◽  
Plasma Total Cholesterol ◽  
Crossover Studies ◽  
Whole Egg

Whole egg is a food source of dietary cholesterol and inconsistent research findings exist about the effect of dietary cholesterol from whole egg on blood cholesterol concentration. We assessed the effect of co-consuming cooked whole egg (CWE) on dietary cholesterol absorption from two randomized-crossover studies. For study 1, 16 men consumed raw vegetables with no egg, 75 g CWE, or 150 g CWE. For study 2, 17 women consumed cooked vegetables with no egg or 100 g CWE. Triacylglycerol-rich lipoprotein fractions (TRL) were isolated from collected blood. In study 1, total-cholesterol areas under the curve (AUC)0–10h in TRL were not different but triacylglycerol AUC0–10h in TRL was greater for 150 g CWE vs. 75 g CWE and no egg. Similarly, in study 2, total-cholesterol AUC0–10h in TRL was not different but triacylglycerol AUC0–10h in TRL was greater for 100 g CWE vs. no egg. In both studies, whole egg consumption did not affect plasma total-cholesterol AUC0–10h, while triacylglycerol AUC0–10h was increased. These results suggest that the dietary cholesterol in whole egg was not well absorbed, which may provide mechanistic insight for why it does not acutely influence plasma total-cholesterol concentration and is not associated with longer-term plasma cholesterol control.

scholarly journals Effects of Nori- and Wakame-enriched meats with or without supplementary cholesterol on arylesterase activity, lipaemia and lipoproteinaemia in growing Wistar rats

2011 ◽  
Vol 106 (10) ◽  
pp. 1476-1486 ◽  
Author(s):  
Raúl Olivero-David ◽  
Adriana Schultz-Moreira ◽  
Miguel Vázquez-Velasco ◽  
Laura González-Torres ◽  
Sara Bastida ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Control Group ◽  
Vldl Cholesterol ◽  
Freeze Dried ◽  
Cholesterol Supplementation ◽  
Two Parameters

Some seaweeds exert antioxidant and hypocholesterolaemic properties. The effects of diets including restructured meats (RM) containing Wakame (W) or Nori (N) algae on arylesterase (AE) activity and lipoprotein concentration and composition were tested. In the present study, six groups of ten male growing Wistar rats each were fed a mix of 85 % AIN-93M diet and 15 % freeze-dried RM for 35 d. The control group (C) consumed control RM, the W and N groups consumed RM with 5 % W and 5 % N, respectively. The cholesterol-enriched C (CC), W (CW) and N (CN) groups consumed their corresponding basal diets with supplementary cholesterol (2·43 %) and cholic acid (0·49 %). Cholesterol in the diet induced lower (P < 0·001) growth ratios. Both W and N diets significantly increased AE activity. VLDL-cholesterol values were lower in N rats than in W rats. AE activity increased (P < 0·001) in CC and CW rats but not in CN rats compared with their corresponding counterparts. AE was lower (P < 0·05) in the CN group than in the CC and CW groups. The CN diet partially blocked (P < 0·001) the hypercholesterolaemic induction observed in CC and CW diets and reduced TAG levels (at least P < 0·05) with respect to those of CC rats. Although dietary cholesterol supplementation increased total cholesterol, VLDL-cholesterol and (intermediate-density lipoprotein+LDL)-cholesterol (all P < 0·001) in all rats, the CN diet moderately improved the lipoprotein profile of hypercholesterolaemic rats. Changes in AE activity and plasma cholesterol in CN rats but not in CW rats suggest a possible relationship between the two parameters. It is concluded that inclusion of RM enriched with N may be used in hypercholesterolaemic diets to improve lipoprotein metabolism.

Dietary cholesterol: from physiology to cardiovascular risk

2011 ◽  
Vol 106 (1) ◽  
pp. 6-14 ◽  
Author(s):  
Jean-Michel Lecerf ◽  
Michel de Lorgeril
Keyword(s):  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Ldl Receptor ◽  
Epidemiological Data ◽  
Cholesterol Absorption ◽  
Cholesterol Content ◽  
Biological Data ◽  
Related Protein ◽  
Cvd Risk ◽  
Nutritional Factors

Dietary cholesterol comes exclusively from animal sources, thus it is naturally present in our diet and tissues. It is an important component of cell membranes and a precursor of bile acids, steroid hormones and vitamin D. Contrary to phytosterols (originated from plants), cholesterol is synthesised in the human body in order to maintain a stable pool when dietary intake is low. Given the necessity for cholesterol, very effective intestinal uptake mechanisms and enterohepatic bile acid and cholesterol reabsorption cycles exist; conversely, phytosterols are poorly absorbed and, indeed, rapidly excreted. Dietary cholesterol content does not significantly influence plasma cholesterol values, which are regulated by different genetic and nutritional factors that influence cholesterol absorption or synthesis. Some subjects are hyper-absorbers and others are hyper-responders, which implies new therapeutic issues. Epidemiological data do not support a link between dietary cholesterol and CVD. Recent biological data concerning the effect of dietary cholesterol on LDL receptor-related protein may explain the complexity of the effect of cholesterol on CVD risk.

scholarly journals SREBP2 mediates the modulation of intestinal NPC1L1 expression by curcumin

2011 ◽  
Vol 301 (1) ◽  
pp. G148-G155 ◽  
Author(s):  
Pradeep Kumar ◽  
Pooja Malhotra ◽  
Ke Ma ◽  
Amika Singla ◽  
Omar Hedroug ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Promoter Activity ◽  
Plasma Cholesterol ◽  
Biological Effects ◽  
Cholesterol Absorption ◽  
Inhibitory Effect ◽  
Cholesterol Homeostasis ◽  
Cholesterol Esterification ◽  
Dependent Manner ◽  
Intestinal Cholesterol Absorption

Curcumin, the major phenolic compound in the spice turmeric, exhibits numerous biological effects, including lowering plasma cholesterol and preventing diet-induced hypercholesterolemia. The mechanisms underlying the hypocholesterolemic effect of curcumin are not fully understood. In this regard, intestinal Niemann-Pick C1-like 1 (NPC1L1) cholesterol transporter, the molecular target of intestinal cholesterol absorption inhibitor ezetimibe, plays an essential role in the maintenance of cholesterol homeostasis. The current studies were designed to investigate the effect of curcumin on NPC1L1 function, expression, and promoter activity in intestinal Caco-2 monolayers. NPC1L1 function was evaluated by the measurement of ezetimibe-sensitive [3H]cholesterol esterification. Relative abundance of NPC1L1 mRNA and protein was evaluated by real-time PCR and Western blotting, respectively. Luciferase assays were used to measure NPC1L1 promoter activity. Our results showed that curcumin significantly inhibited ezetimibe-sensitive cholesterol esterification in a dose-dependent manner with a maximum decrease (by 52% compared with control) occurring at 50 μM concentration. Curcumin treatment of Caco-2 monolayers also significantly decreased NPC1L1 mRNA and protein expression. Similarly, the promoter activity of the NPC1L1 gene was inhibited significantly (55%) by 50 μM curcumin. The decrease in NPC1L1 promoter activity by curcumin was associated with a reduction in the expression and the DNA-binding activity of the sterol response element-binding protein 2 (SREBP2) transcription factor. Furthermore, the overexpression of active SREBP2 protected NPC1L1 from the inhibitory effect of curcumin. Our studies demonstrate that curcumin directly modulates intestinal NPC1L1 expression via transcriptional regulation and the involvement of SREBP2 transcription factor.

The role of diet during development on the regulation of adult cholesterol homeostasis

1985 ◽  
Vol 63 (5) ◽  
pp. 557-564 ◽  
Author(s):  
Sheila M. Innis
Keyword(s):  
Cholesterol Metabolism ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Homeostasis ◽  
Cholesterol Levels ◽  
Effective Training ◽  
Cholesterol Intake ◽  
Lower Plasma Cholesterol ◽  
Altered Metabolism

Atherosclerosis is believed to begin early in life and to develop over several decades. Elevated plasma cholesterol is a major contributing factor. Studies in animals have shown that manipulation of cholesterol metabolism during its development in pre-and early post-natal life can permanently alter cholesterol synthesis and catabolism to favour lower plasma cholesterol levels in the adult faced with a high dietary cholesterol intake. Although the mechanisms and pathways involved are likely to be different, "metabolic training" can occur as a result of both the diet fed to the mother during gestation and lactation and from the diet fed to the animal itself in early life. The presence of cholesterol itself in the suckling diet does not appear to confer any lasting improvement to cholesterol handling in either man or animals. Although much research is still required to define the time in development for effective training of specific steps in cholesterol metabolism and the primary site and mechanism of permanently altered metabolism, significant progress has been made. These studies will form the basis of this review.

scholarly journals Genetic and physiological aspects of cholesterol accumulation in hyperresponding and hyporesponding rabbits

1981 ◽  
Vol 15 (1) ◽  
pp. 61-68 ◽  
Author(s):  
L. F. M. Van Zutphen ◽  
M. G. C. W. Den Bieman ◽  
W. C. HÜLsmann ◽  
R. R. Fox
Keyword(s):  
Lipoprotein Lipase ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Adrenal Weight ◽  
Cholesterol Accumulation ◽  
Cholesterol Levels ◽  
Total Body

After a 5 week period of feeding a cholesterol-rich diet to rabbits, hyperresponders with high plasma cholesterol levels and hyporesponders with low plasma cholesterol levels could be distinguished from normal responders. The response was found to be correlated with the esterase genotype at the Est-2 locus. The increase in total body cholesterol was higher in hyper- than in hyporesponders. In both groups most of the accumulated dietary cholesterol was found in plasma and liver. Adrenal weight and plasma corticosterone levels were more increased in hyper- than in hyporesponders. The cholesterol-rich diet resulted in an augmentation of liver lipase and lipoprotein lipase activities. These lipolytic activities were more increased in hyper- than in the hyporesponders.

scholarly journals Familial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease

2018 ◽  
Vol 19 (11) ◽  
pp. 3426 ◽  
Author(s):  
Asier Benito-Vicente ◽  
Kepa Uribe ◽  
Shifa Jebari ◽  
Unai Galicia-Garcia ◽  
Helena Ostolaza ◽  
...  
Keyword(s):  
Familial Hypercholesterolemia ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Plasma Cholesterol ◽  
Dietary Cholesterol ◽  
Cholesterol Homeostasis ◽  
Hereditary Diseases ◽  
Special Focus ◽  
Peripheral Tissues ◽  
Premature Cardiovascular Disease

Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol metabolism must be tightly controlled. Cell cholesterol is mainly acquired from two sources: Dietary cholesterol, which is absorbed in the intestine and, intracellularly synthesized cholesterol that is mainly synthesized in the liver. Once acquired, both are delivered to peripheral tissues in a lipoprotein dependent mechanism. Malfunctioning of cholesterol metabolism is caused by multiple hereditary diseases, including Familial Hypercholesterolemia, Sitosterolemia Type C and Niemann-Pick Type C1. Of these, familial hypercholesterolemia (FH) is a common inherited autosomal co-dominant disorder characterized by high plasma cholesterol levels. Its frequency is estimated to be 1:200 and, if untreated, increases the risk of premature cardiovascular disease. This review aims to summarize the current knowledge on cholesterol metabolism and the relation of FH to cholesterol homeostasis with special focus on the genetics, diagnosis and treatment.

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