Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids

Iglesias, Angel; Arranz, M.L.; Álvarez, Juan José Criado; Perales, José C.; Villar, Juan Carlos; Herrera, Emílio; Lasunción, Miguel A.

doi:10.1016/0009-8981(95)06251-3

Cited by 30 publications

(15 citation statements)

References 54 publications

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“…Thus far, only a few studies addressed alterations of CETP in patients with increased plasma BA compared with controls. One study assessed CETP activity in patients with cholestasis and found, in contrast to our study, a decrease in CETP activity compared with control subjects ( 34 ). However, in that study, controls were not carefully matched and decreased hepatic protein synthesis capacity in the patient group might conceivably represent a confounding factor, explaining the difference between these previous results and our study.…”

Section: Fxr Activation Involves An Er8 Element In the Fi Rst Intron contrasting

confidence: 99%

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Gautier

Haan

Grober

et al. 2013

Journal of Lipid Research

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The cholesteryl ester transfer protein (CETP) promotes the heteroexchange of cholesteryl esters and triglycerides (TG) between plasma high density lipoproteins (HDL) and apoB-containing lipoproteins, resulting in a proatherogenic plasma lipid profi le with increased VLDL and LDL cholesterol levels and decreased HDL cholesterol (HDL-C) ( 1, 2 ). Given the key importance of dyslipidemia for the development of atherosclerosis ( 3 ), most ( 1, 2, 4-6 ) but Abstract Cholesteryl ester transfer protein (CETP) activity results in a proatherogenic lipoprotein profi le. In cholestatic conditions, farnesoid X receptor (FXR) signaling by bile acids (BA) is activated and plasma HDL cholesterol (HDL-C) levels are low. This study tested the hypothesis that FXR-mediated induction of CETP contributes to this phenotype. Patients with cholestasis and high plasma BA had lower HDL-C levels and higher plasma CETP activity and mass compared with matched controls with low plasma BA (each P < 0.01). BA feeding in APOE3*Leiden transgenic mice expressing the human CETP transgene controlled by its endogenous promoter increased cholesterol within apoBcontaining lipoproteins and decreased HDL-C (each P < 0.01), while hepatic CETP mRNA expression and plasma CETP activity and mass increased (each P < 0.01). In vitro studies confi rmed that FXR agonists substantially augmented CETP mRNA expression in hepatocytes and macrophages dependent on functional FXR expression (each P < 0.001). These transcriptional effects are likely mediated by an ER8 FXR response element (FXRE) in the fi rst intron. In conclusion, using a translational approach, this study identifi es CETP as novel FXR target gene. By increasing CETP expression, FXR activation leads to a proatherogenic

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Section: Fxr Activation Involves An Er8 Element In the Fi Rst Intron contrasting

confidence: 99%

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Gautier

Haan

Grober

et al. 2013

Journal of Lipid Research

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“…Biliary tumors, like biliary stones, can cause chronic cholestasis due to bile duct obstruction, which presents with jaundice and is associated with increased serum levels of total cholesterol, triglycerides and LDL, and decreased HDL. 27 In our study, the excess risks of gallbladder cancer in relation to high triglycerides and low HDL persisted after exclusion of gallbladder cancer cases with jaundice. We were unable to assess whether the risks of bile duct and ampulla of Vater cancers were affected by jaundice, since over 85% of these cancer cases had jaundice at the time of diagnosis.…”

Section: Table III -Odds Ratios (Ors) and 95% Confidence Intervals (Csupporting

confidence: 44%

“…Omnibus null hypothesis that odds ratios are all equal to 1. els of bilirubin), and is associated with increased serum levels of total cholesterol, triglycerides and LDL, as well as decreased HDL. 27 We found that the association of high triglycerides, low HDL and low apo A with biliary stones persisted after biliary stone cases with jaundice were excluded from the analysis. We also assessed the effects of weight loss and dietary changes, which are possible consequences of biliary stones that are usually related to decreased levels of total cholesterol, triglycerides, and LDL and increased levels of HDL.…”

Section: Discussionmentioning

confidence: 78%

Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population‐based study in China

Andreotti

Chen

Gao

et al. 2007

Intl Journal of Cancer

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Biliary tract cancers, encompassing the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. Gallstones, the predominant risk factor for biliary cancers, are linked with hyperlipidemia. As part of a populationbased case-control study conducted in Shanghai, China, we examined the associations of serum lipid levels with biliary stones and cancers. We included 460 biliary cancer cases (264 gallbladder, 141 extrahepatic bile duct, and 55 ampulla of Vater), 981 biliary stone cases and 858 healthy individuals randomly selected from the population. Participants completed an in-person interview and gave overnight fasting blood samples. Participants in the highest quintile of triglycerides (≥160 mg/dl) had a 1.4-fold risk of biliary stones (95% CI 5 1.1-1.9), a 1.9-fold risk of gallbladder cancer (95% CI 5 1.3-2.8), and a 4.8-fold risk of bile duct cancer (95% CI 5 2.8-8.1), compared to the reference group (third quintile: 90-124 mg/dl). Participants in the lowest quintile of high-density lipoprotein (HDL) (<30 mg/dl) had a 4.2-fold risk of biliary stones (95% CI 5 3.0-6.0), an 11.6-fold risk of gallbladder cancer (95% CI 5 7.3-18.5), and a 16.8-fold risk of bile duct cancer (95% CI 5 9.1-30.9), relative to the reference group (third quintile: 40-49 mg/dl). In addition, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A (apo A) were inversely associated with biliary stones; whereas low levels as well as high levels of total cholesterol, LDL, apo A and apolipoprotein B (apo B) were associated with excess risks of biliary tract cancers. Our findings support a role for serum lipids in gallstone development and biliary carcinogenesis. ' 2007 Wiley-Liss, Inc.Key words: serum lipid levels; gallstones; biliary tract cancer Biliary tract cancers, consisting of tumors of the gallbladder, extrahepatic bile ducts and ampulla of Vater, are rare but highly fatal malignancies. 1,2 Gallstones are the most important known risk factor for all three biliary tract cancer subsites. Specifically, cholesterol gallstones (composed mainly of cholesterol) and mixed gallstones (composed of both cholesterol and bilirubin) are most strongly associated with gallbladder cancer. 2,3 Furthermore, cholesterol gallstones and gallbladder cancer share a number of putative risk factors, including obesity, high fat diet and hyperlipidemia. 2,4 Hyperlipidemia is generally characterized by high serum levels of total cholesterol, triglycerides, low-density-lipoprotein (LDL), and low levels of high-density-lipoprotein (HDL). High triglycerides and low HDL have been most consistently associated with gallstones, whereas the associations of total cholesterol and LDL with gallstones are less consistent. [5][6][7] Cholesterol gallstone pathogenesis involves cholesterol saturation of the bile duct due to the hypersecretion of cholesterol from the liver 8 ; however, the exact role of individual lipids, lipoproteins and apolipoproteins is less clear.Given the relationship between hyperlipidemia and gallsto...

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“…The outer collagenous layer showed a more complicated pattern, with ( 96 ). HDL EC is reported for 20 normolipemic volunteers ( 199 ). Fatty acids in photoreceptor outer segment phospholipids taken from ( 134 ).…”

Section: Ec-rich Barrier In Aged Brm; Lipid Wallmentioning

confidence: 99%

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

Curcio

Johnson

Huang

et al. 2010

Journal of Lipid Research

164

143

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Cholesteryl ester transfer activity in liver disease and cholestasis, and its relation with fatty acid composition of lipoprotein lipids

Cited by 30 publications

References 54 publications

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice

Serum lipid levels and the risk of biliary tract cancers and biliary stones: A population‐based study in China

Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

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