Abstract 19836: Lipid Metabolism is Modified by the Interaction Between Cholesteryl Ester Transfer Protein Gene Polymorphism and Mediterranean Diet in Patients in Secondary Prevention for Cardiovascular Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Antonio Garcia Rios ◽  
Francisco Gomez-Delgado ◽  
Ana Isabel Perez Caballero ◽  
Andreea Corina-Baba ◽  
Vanesa Navarro-Martos ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Lipid Metabolism ◽  
Cholesteryl Ester ◽  
Mediterranean Diet ◽  
Cholesteryl Ester Transfer Protein ◽  
Dietary Intervention ◽  
Intervention Group ◽  
Low Fat ◽  
Transfer Protein ◽  
The Impact

Introduction: Cholesteryl ester transfer protein (CETP) gene has been implicated in lipid metabolism. However, little is known about the impact of this gene on coronary heart disease (CHD) patients and its interaction with diet. Hypothesis: To evaluate whether the chronic consumption of a Mediterranean diet enriched in olive oil, compared with a Low fat diet, interacts with the rs3764261 SNP at CETP locus in order to modify lipid metabolism among MetS patients from the CORDIOPREV clinical trial Methods: Plasma lipid concentrations and rs3764261 genotypes were determined in 424 MetS subjects participating in the CORDIOPREV clinical trial. Gene-diet interactions were analyzed after a year of dietary intervention (Mediterranean diet (35% fat, 22% MUFA) vs Low fat diet (28% fat, 12% MUFA)) Results: We found significant gene-diet interactions between rs3764261 SNP and the dietary pattern for HDL-C ( P=0.006 ) and triglyceride concentrations ( P=0.040 ). Specifically, after 12 months of Mediterranean diet intervention, subjects who were carriers of the minor T allele (TT+TG) displayed higher plasma HDL-C concentrations ( P=0.021 ) and lower triglycerides ( P=0.020 ) compared with homozygous for the major allele (GG). In contrast, in the Low fat intervention group no significant differences were found between CETP genotypes after 12 months of dietary treatment. Conclusions: Our data support the notion that a chronic consumption of a Mediterranean diet may play a contributing role in triggering lipid metabolism by interacting with the rs3764261 SNP at CETP gene locus in MetS patients

Low-fat dietary pattern and long-term breast cancer incidence and mortality: The Women’s Health Initiative randomized clinical trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 520-520 ◽  
Author(s):  
Rowan T. Chlebowski ◽  
Aaron K Aragaki ◽  
Garnet L Anderson ◽  
Kathy Pan ◽  
Marian L Neuhouser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Dietary Pattern ◽  
Dietary Intervention ◽  
Breast Cancer Incidence ◽  
Intervention Group ◽  
Fat Intake ◽  
Breast Cancers ◽  
Low Fat ◽  
Cancer Breast

520 Background: Observational studies of dietary fat intake and breast cancer have inconsistent findings. To address this issue, the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial assessed a low-fat dietary pattern influence on breast cancer incidence and outcome. Methods: The WHI DM trial is a randomized, controlled clinical trial conducted at 40 US centers, where 48,835 postmenopausal women, aged 50-79 years, with no previous breast cancer and dietary fat intake ≥32% of total energy, were randomly assigned, from 1993-1998, to a usual diet comparison group (60%) or dietary intervention group (40%) with goals to reduce fat intake to 20% of energy and increase vegetables, fruit, and grain intake. This study is registered as: NCT00000611. Results: The dietary intervention significantly reduced fat intake; increased fruit, vegetable and grain intake with modest weight loss (3%) (all P< 0.001). During 8.5 years of dietary intervention, there were 8% fewer breast cancers and deaths from breast cancer were somewhat lower in the intervention group but the rates were not significantly different. However, deaths after breast cancer (breast cancer followed by death from any cause) were significantly reduced in the intervention group, both during intervention (hazard ratio [HR] 0·65 95% confidence interval [CI] 0·45-0·95) and through 16.1 year (median) cumulative follow-up. Now, after long- term, cumulative 19.6 year (median) follow-up, with 3,374 incident breast cancers, the significant reduction in deaths after breast cancer continued (with 1,011 deaths, HR 0·85 95% CI 0·74-0·96) and a significant reduction in deaths from breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (with 383 deaths, HR 0·79 95% CI 0·64-0·97). Conclusions: Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, significantly reduced the risk of death from breast cancer in postmenopausal women. To our review, these findings provide the first randomized clinical trial evidence that a dietary change can reduce a postmenopausal woman’s risk of dying from breast cancer. Clinical trial information: NCT00000611.

scholarly journals The Cholesteryl Ester Transfer Protein (CETP) raises Cholesterol Levels in the Brain and affects Presenilin-mediated Gene Regulation

2020 ◽  
Author(s):  
Felix Oestereich ◽  
Noosha Yousefpour ◽  
Ethan Yang ◽  
Alfredo Ribeiro-da-Silva ◽  
Pierre Chaurand ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Cholesterol Metabolism ◽  
High Cholesterol Diet ◽  
Transfer Protein ◽  
Brain Functions ◽  
Cholesterol Levels ◽  
Ldl Particles ◽  
The Impact ◽  
The Brain

AbstractThe cholesteryl ester transfer protein (CETP) is a lipid transfer protein responsible for the exchange of cholesteryl esters and triglycerides between lipoproteins. Decreased CETP activity is associated with longevity, cardiovascular health, and maintenance of good cognitive performance. Interestingly, mice lack the CETP-encoding gene and have very low levels of low-density lipoprotein (LDL) particles compared to humans. To understand how CETP activity affects the brain, we utilised CETP transgenic (CETPtg) mice showing elevated LDL levels on a high cholesterol diet inducing CETP expression. We found that CETPtg mice had up to 25% higher cholesterol levels in the brain. Using a microarray on astrocyte-derived mRNA, we found that this cholesterol increase is likely not due to astrocytic-dependent de novo synthesis of cholesterol. Rather, several genes linked to Alzheimer’s disease were altered in CETPtg mice. Most interestingly, we found activation of the G-protein coupled receptor EP4 and γ-secretase as upstream regulators of these transcriptional changes. Further in vitro studies showed that CETP expression was sufficient to activate γ-secretase activity. The data suggest that CETP activity affects brain’s health through modulating cholesterol levels and Alzheimer’s-related pathways. Therefore, CETPtg mice constitute a valuable research tool to investigate the impact of the cholesterol metabolism on brain functions.

scholarly journals Cholesteryl ester transfer protein: the physiological and molecular characteristics in the pathogenesis of atherosclerosis and Alzheimer’s disease

2019 ◽  
Vol 73 ◽  
pp. 387-396
Author(s):  
Justyna Pawlik ◽  
Dorota Wrześniok
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cardiovascular Diseases ◽  
Cholesteryl Ester ◽  
Lipid Profile ◽  
Cholesteryl Ester Transfer Protein ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Transfer Protein ◽  
The Impact

Cholesteryl ester transfer protein (CETP) is involved in reverse cholesterol transport, mediates the exchange of cholesteryl esters for triglycerides between high-density lipoproteinsand low-density lipoproteins/very low-density lipoproteins. Lipid transfer mechanism by CETP is unknown. Two main models have been proposed for the mechanism of action of CETP: shuttle and tunnel mechanisms. The variants of CETP gene affect activity and level of protein, thus they are associated with lipid profile and risk of many diseases. Some clinical studies reported that polymorphisms of CETP, including TaqIB and I405V, are associated with risk of atherosclerosis and/or Alzheimer’s disease. CETP plays important role an in the metabolism of cholesterol, thus is correlated with pathomechanism of coronary artery disease. Inhibition of CETP can be an effective strategy to improve the lipid profile and reduce risk of cardiovascular diseases. Therefore, new therapeutic strategies to reduce activity of CETP or decrease its level are developed. Effectiveness of following pharmacological methods of modulation of CETP activity was studied: anti-CETP vaccines, antisense oligonucleotide and small molecule inhibitors of CETP. This article presents an overview of the literature on the correlation between cardiovascular diseases and CETP protein/CETP gene. Furthermore, it discusses the impact of CETP on pathogenesis of Alzheimer’s disease.

scholarly journals Simultaneous Determination of Biliary and Intestinal Cholesterol Secretion Reveals That CETP (Cholesteryl Ester Transfer Protein) Alters Elimination Route in Mice

2019 ◽  
Vol 39 (10) ◽  
pp. 1986-1995 ◽  
Author(s):  
Jianing Li ◽  
Sonja S. Pijut ◽  
Yuhuan Wang ◽  
Ailing Ji ◽  
Rupinder Kaur ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Density Lipoprotein ◽  
High Fat ◽  
Biliary Cholesterol ◽  
Transfer Protein ◽  
Biliary Cholesterol Secretion ◽  
Cholesterol Secretion ◽  
The Impact

Objective: Determine the impact of CETP (cholesteryl ester transfer protein) on the route of cholesterol elimination in mice. Approach and Results: We adapted our protocol for biliary cholesterol secretion with published methods for measuring transintestinal cholesterol elimination. Bile was diverted and biliary lipid secretion maintained by infusion of bile acid. The proximal small bowel was perfused with bile acid micelles. In high-fat, high-cholesterol–fed mice, the presence of a CETP transgene increased biliary cholesterol secretion at the expense of transintestinal cholesterol elimination. The increase in biliary cholesterol secretion was not associated with increases in hepatic SR-BI (scavenger receptor BI) or ABCG5 (ATP-binding cassette G5) ABCG8. The decline in intestinal cholesterol secretion was associated with an increase in intestinal Niemann-Pick disease, type C1, gene-like 1 mRNA. Finally, we followed the delivery of HDL (high-density lipoprotein) or LDL (low-density lipoprotein) cholesteryl esters (CE) from plasma to bile and intestinal perfusates. HDL-CE favored the biliary pathway. Following high-fat feeding, the presence of CETP directed HDL-CE away from the bile and towards the intestine. The presence of CETP increased LDL-CE delivery to bile, whereas the appearance of LDL-CE in intestinal perfusate was near the lower limit of detection. Conclusions: Biliary and intestinal cholesterol secretion can be simultaneously measured in mice and used as a model to examine factors that alter cholesterol elimination. Plasma factors, such as CETP, alter the route of cholesterol elimination from the body. Intestinal and biliary cholesterol secretion rates are independent of transhepatic or transintestinal delivery of HDL-CE, whereas LDL-CE was eliminated almost exclusively in the hepatobiliary pathway.

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