Regulation of plasma cholesterol esterification by sphingomyelin: Effect of physiological variations of plasma sphingomyelin on lecithin-cholesterol acyltransferase activity

Subbaiah, Papasani V.; Jiang, Xian Cheng; Belikova, Natalia A.; Aizezi, Buzulagu; Huang, Zhenjun; Reardon, Catherine A.

doi:10.1016/j.bbalip.2012.02.007

Cited by 33 publications

(20 citation statements)

References 45 publications

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“…Major cholesteryl ester species (CE 18:2, 18:3, 20:3, and 20:4) were not altered (data not shown). Since in mice acyl coenzyme A: cholesteryl acyltransferase (ACAT) prefers saturated and monounsaturated fatty acids for esterification and lecithin-cholesterol acyltransferase (LCAT) prefers polyunsaturated fatty acids, the distribution of saturated and monounsaturated with polyunsaturated fatty acids in CE was compared by calculating the ratio of saturated + monounsaturated on polyunsaturated CE [30, 31]. This ratio was decreased in the SNTA/B2 null mice (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Hebel

Eisinger

Neumeier

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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The syntrophins alpha (SNTA) and beta 2 (SNTB2) are molecular adaptor proteins shown to stabilize ABCA1, an essential regulator of HDL cholesterol. Furthermore, SNTB2 is involved in glucose stimulated insulin release. Hyperglycemia and dyslipidemia are characteristic features of the metabolic syndrome, a serious public health problem with rising prevalence. Therefore, it is important to understand the role of the syntrophins herein. Mice deficient for both syntrophins (SNTA/B2−/−) have normal insulin and glucose tolerance, hepatic ABCA1 protein and cholesterol. When challenged with a HFD, wild type and SNTA/B2−/− mice have similar weight gain, adiposity, serum and liver triglycerides. Hepatic ABCA1, serum insulin and insulin sensitivity are normal while glucose tolerance is impaired. Liver cholesterol is reduced, and expression of SREBP2 and HMG-CoA-R is increased in the knockout mice. Scavenger receptor-BI (SR-BI) protein is strongly diminished in the liver of SNTA/B2−/− mice while SR-BI binding protein NHERF1 is not changed and PDZK1 is even induced. Knock-down of SNTA, SNTB2 or both has no effect on hepatocyte SR-BI and PDZK1 proteins. Further, SR-BI levels are not reduced in brown adipose tissue of SNTA/B2−/− mice excluding that syntrophins directly stabilize SR-BI. SR-BI stability is regulated by MAPK and phosphorylated ERK2 is induced in the liver of the knock-out mice. Blockage of ERK activity upregulates hepatocyte SR-BI showing that increased MAPK activity contributes to low SR-BI. Sphingomyelin which is well described to regulate cholesterol metabolism is reduced in the liver and serum of the knock-out mice while the size of serum lipoproteins is not affected. Current data exclude a major function of these syntrophins in ABCA1 activity and insulin release but suggest a role in regulating glucose uptake, ERK and SR-BI levels, and sphingomyelin metabolism in obesity.

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Section: Resultsmentioning

confidence: 99%

“…Sphingomyelin (SM) is a highly abundant serum lipid shown to affect cholesterol esterification and uptake by the liver [31–33]. In serum of SNTA/B2−/− mice SM was strongly reduced (Fig.…”

Section: Resultsmentioning

confidence: 99%

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Hebel

Eisinger

Neumeier

et al. 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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“…Measurement of LCAT enzyme activity instead is complicated and not usable for clinical routine because LCAT activity is influenced by the level of ApoAI, HDL [19], sphingomyelin and phosphatidylcholine in vivo [23]. In the reaction of cholesterol esterification the abnormal lipoprotein X (LP-X) [24] has been described also.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality

et al. 2017

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BackgroundAdvanced stages of liver cirrhosis lead to a dramatically increased mortality. For valid identification of these patients suitable biomarkers are essential. The most important biomarkers for liver function are bilirubin and prothrombin time expressed as International Normalized Ratio (INR). However, the influence of several anticoagulants on the prothrombin time limits its diagnostic value.Aim of this study was the evaluation of cholesterol esterification (CE) fraction (esterified cholesterol vs. total cholesterol) as an alternative biomarker for liver synthesis and mortality prediction. Under physiological conditions the CE fraction in blood is closely regulated by lecithin-cholesterol acyltransferase (LCAT) which is produced in the liver.MethodsOne hundred forty-two patients with liver disease clinically considered for orthotopic liver transplant for different indications were enrolled in the study. One patient was excluded because of the intake of a direct oral factor Xa inhibitor which has a strong impact on prothrombin time.ResultsResults of CE fraction were in good agreement with INR (R2 = 0.73; p < 0.001). In patients who died or survived within three months mean CE fraction was 56% vs. 74% (p < 0.001) and mean INR was 2.0 vs. 1.3 (p < 0.001), respectively. The predictive value of CE fraction for three-month mortality risk was higher compared to INR (p = 0.04). Results for one-year mortality were comparable.ConclusionsThe cholesterol esterification fraction is a valid biomarker for liver synthesis and allows reliable prediction of mortality. In contrast to INR, it is independent of anticoagulation and other analytical limitations of coagulation tests.Electronic supplementary materialThe online version of this article (doi:10.1186/s12876-017-0614-9) contains supplementary material, which is available to authorized users.

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“…On the other hand, HDL SM is elevated in patients with isolated arterial hypertension ( 90 ) and with psoriasis ( 92 ). Interestingly, SM enrichment in HDL may selectively inhibit generation of specifi c molecular species of cholesteryl esters catalyzed by LCAT, altering the plasma profi le of cholesteryl esters ( 106 ).…”

Section: Sphingolipidsmentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

310

254

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This article is available online at http://www.jlr.org For many years, HDL lipids were predominantly characterized in terms of the content of their major classes, notably phospholipids, unesterifi ed (free) sterols (predominantly cholesterol), cholesteryl esters, and triglycerides. Cholesterol is the most characteristic component of the HDL lipidome as, in the form of HDL-cholesterol, it represents a major independent negative risk factor for cardiovascular disease (see other reviews in this Thematic Series). It is not cholesterol, however, but phospholipids that quantitatively predominate in the HDL lipidome, accounting, together with sphingomyelin (SM), for 40-60 wt% of total lipid, with lesser proportions of cholesteryl esters (30-40%), triglycerides (5-12%), and free cholesterol (5-10%). Structurally, individual HDL lipid classes fulfi ll distinct functions; phospholipids constitute the surface lipid monolayer of HDL, whereas cholesteryl esters and triglycerides form the hydrophobic lipid core. Unesterifi ed sterols are predominantly located to the surface monolayer, partially penetrating the core.Recent technological advances in mass spectrometry (MS) have enabled application of this powerful technique to provide a detailed identifi cation and quantifi cation of individual molecular species of lipids in the framework of the fi eld known as lipidomics. Application of this approach to plasma lipoproteins has revealed complex profi les consisting of hundreds of molecular lipid species that have been quantifi ed in major lipoprotein classes, including HDL (reviewed in Refs. 1-3 High density lipoproteins (HDL) are small, dense, protein-rich particles compared with other plasma lipoprotein classes. Despite the elevated abundance of multiple structural and functional proteins in HDL particles (see other reviews in this Thematic Series), roughly half of total HDL mass is accounted for by lipid components.

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Regulation of plasma cholesterol esterification by sphingomyelin: Effect of physiological variations of plasma sphingomyelin on lecithin-cholesterol acyltransferase activity

Cited by 33 publications

References 45 publications

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Lipid abnormalities in alpha/beta2-syntrophin null mice are independent from ABCA1

Cholesterol esterification in plasma as a biomarker for liver function and prediction of mortality

Unraveling the complexities of the HDL lipidome

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