Distribution of diacylglycerols among plasma lipoproteins in control subjects and in patients with non‐insulin‐dependent diabetes

Lalanne, Florent; Pruneta, V.; Bernard, Sophie; Ponsin, Gabriel

doi:10.1046/j.1365-2362.1999.00438.x

Cited by 21 publications

(16 citation statements)

References 26 publications

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“…Minor bioactive HDL lipids include diacylglycerides, monoacylglicerides, and free fatty acids ( 4,31,32,38,39 ). Lipidomic characterization of these lipid classes in HDL remains to be performed.…”

Section: Minor Lipidsmentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

310

247

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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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Section: Minor Lipidsmentioning

confidence: 99%

Unraveling the complexities of the HDL lipidome

Kontush

Lhomme

Chapman

2013

Journal of Lipid Research

310

247

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“…LDL Moderate LPIN3 is one of three lipin genes; lipin genes catalyze the synthesis of diacylglycerols 51 , constituents of LDL and other lipoproteins 52 and intermediates in the synthesis of multiple classes of lipids 53 .…”

Section: Lpin3mentioning

confidence: 99%

Transcriptome-wide association studies: opportunities and challenges

Wainberg

Sinnott-Armstrong

Mancuso

et al. 2017

Preprint

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Transcriptome-wide association studies (TWAS) integrate GWAS and expression quantitative trait locus (eQTL) datasets to discover candidate causal gene-trait associations. We integrate multi-tissue expression panels and summary GWAS for LDL cholesterol and Crohn's disease to show that TWAS are highly vulnerable to discovering non-causal genes, because variants at a single GWAS hit locus are often eQTLs for multiple genes. TWAS exhibit acute instability when the tissue of the expression panel is changed: candidate causal genes that are TWAS hits in one tissue are usually no longer hits in another, due to lack of expression or strong eQTLs, while non-causal genes at the same loci remain. While TWAS is statistically valid when used as a weighted burden test to identify trait-associated loci, it is invalid to interpret TWAS associations as causal genes because the false discovery rate for TWAS causal gene discovery is not only high, but unquantifiable. More broadly, our results showcase limitations of using expression variation across individuals to determine causal genes at GWAS loci.

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“…DG was not shown to be confined to the lipoprotein core like TG, but was predominantly localized on the lipoprotein surface. While this is still considered somewhat controversial, other groups have made similar observations (9,15). In addition, DG has been shown to be the primary substrate for human hepatic lipase (HL) and the amount Abbreviations: apoA-I, apolipoprotein A-I; CD, circular dichroism; CE, cholesteryl ester; DG, diacylglycerol; ED 50 , particle concentration required for 50% inhibition of maximal antibody binding; FC, free (unesterified) cholesterol; GGE, gradient gel electrophoresis; HDL, high density lipoprotein; HL, hepatic lipase; LCAT, lecithin:cholesteryl acyltransferase; LpA-I, reconstituted HDL; MAb, monoclonal antibodies; NMR, nuclear magnetic resonance; PBS, phosphate-buffered saline; PL, phospholipid; POPC, palmitoyl-oleoyl phosphatidylcholine; TG, triacylglycerol.…”

mentioning

confidence: 76%

Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

Braschi

Coffill²,

Neville

et al. 2001

Journal of Lipid Research

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The effects of different acylglycerides on the conformation and charge of apolipoprotein A-I (apoA-I) have been investigated in reconstituted high density lipoproteins (LpA-I). Various amounts of diacylglycerol (DG) and triacylglycerol (TG) were incorporated into sonicated spherical LpA-I particles containing 2 molecules of apoA-I and 80 molecules of phospholipid. Inclusion of 30 molecules of TG into the LpA-I particle increases the net negative charge of apoA-I ( ؊ 8.5 to ؊ 9.3 mV), but has little effect on the amount and thermodynamic stability of the ␣ helices in apoA-I. Incorporation of 30 molecules of DG into the lipoprotein complex promotes a small increase in the ␣ -helix content and stability, but greatly increases the net negative charge of apoA-I ( ؊ 8.5 to ؊ 11.2 mV). Inclusion of DG increases the immunoreactivity of two epitopes in the N terminus of apoA-I, but decreases the exposure of a domain closer to the C terminus (residues 148-186) of the apoprotein. In contrast, TG increases the exposure of epitopes over the entire apoA-I molecule; TG increases the immunoreactivity of epitopes for 13 different monoclonal antibodies to apoA-I. Incubations with purified lecithin:cholesterol acyltransferase show that cholesterol esterification is stimulated by DG, but inhibited by TG. The data show that TG and DG have different effects on apoA-I structure and function and this suggests that the TG-to-DG ratio in HDL may directly affect the metabolism of this lipoprotein class. -Braschi, S.

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Distribution of diacylglycerols among plasma lipoproteins in control subjects and in patients with non‐insulin‐dependent diabetes

Abstract: These findings indicate that DAGs are probably formed from TG during lipolysis and that they can be transported to HDL through the action of PLTP. This raises the question whether DAG might act as an inhibitor of phospholipid transfer by competition for binding to PLTP.

Cited by 21 publications

References 26 publications

Unraveling the complexities of the HDL lipidome

Unraveling the complexities of the HDL lipidome

Transcriptome-wide association studies: opportunities and challenges

Effect of acylglyceride content on the structure and function of reconstituted high density lipoprotein particles

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