Dong-Jae Jun
May 1, 2020; 61:746-757
Research Articles

Kristian K Kristensen
Apr 23, 2020; 0:jlr.ILR120000780v1-jlr.ILR120000780
Images in Lipid Research

Naoko Sawada
Apr 14, 2020; 0:jlr.RA119000312v1-jlr.RA119000312
Research Articles

Hyo Jung Kim
May 1, 2020; 61:722-733
Research Articles

Yipeng Sui
May 1, 2020; 61:696-706
Research Articles

Shwetha K. Shetty
Apr 1, 2020; 61:546-559
Methods

Delphine Fontaine
Apr 7, 2020; 0:jlr.RA120000634v1-jlr.RA120000634
Research Articles

Sandi M. Azab
Mar 31, 2020; 0:jlr.D120000630v1-jlr.D120000630
Methods

M John Chapman
Apr 15, 2020; 0:jlr.P119000543v1-jlr.P119000543
Patient-Oriented and Epidemiological Research

Inês Magro dos Reis
Apr 14, 2020; 0:jlr.RA120000632v1-jlr.RA120000632
Research Articles

Inga Nilsson
Mar 10, 2020; 0:jlr.RA120000654v1-jlr.RA120000654
Research Articles

Jeroen van Smeden
Apr 7, 2020; 0:jlr.RA120000639v1-jlr.RA120000639
Research Articles

Eyad Naser
Mar 10, 2020; 0:jlr.RA120000682v1-jlr.RA120000682
Research Articles

Souad Amiar
Apr 15, 2020; 0:jlr.ILR120000753v1-jlr.ILR120000753
Images in Lipid Research

Dmitri Sviridov
May 1, 2020; 61:687-695
Thematic Reviews

Xia Meng
May 1, 2020; 61:591-591
Images in Lipid Research

Zinc is a critical element for insulin storage in the secretory granules of pancreatic beta cells. The islet-specific zinc transporter ZnT8 mediates granular sequestration of zinc ions. A genetic variant of human ZnT8 arising from a single nonsynonymous nucleotide change contributes to increased susceptibility to type-2 diabetes (T2D), but it remains unclear how the high risk variant (Arg-325), which is also a higher frequency (>50%) allele, is correlated with zinc transport activity. Here, we compared the activity of Arg-325 with that of a low risk ZnT8 variant (Trp-325). The Arg-325 variant was found to be more active than the Trp-325 form following induced expression in HEK293 cells. We further examined the functional consequences of changing lipid conditions to mimic the impact of lipid remodeling on ZnT8 activity during insulin granule biogenesis. Purified ZnT8 variants in proteoliposomes exhibited more than 4-fold functional tunability by the anionic phospholipids, lysophosphatidylcholine and cholesterol. Over a broad range of permissive lipid compositions, the Arg-325 variant consistently exhibited accelerated zinc transport kinetics versus the Trp-form. In agreement with the human genetic finding that rare loss-of-function mutations in ZnT8 are associated with reduced T2D risk, our results suggested that the common high risk Arg-325 variant is hyperactive, and thus may be targeted for inhibition to reduce T2D risk in the general populations.

In the inaugural episode of the UK Tech Weekly Podcast host Matt Egan discusses Apple's disastrous Error 53 with David Price, acting editor of Macworld UK. Techworld.com editor Charlotte Jee discusses the London mayoral candidates views on the UK tech industry, including Zach Goldsmith's anti-Uber statement, and online editor Scott Carey jumps in with some inane ideas around fibre broadband. Finally the team talk about YouTube licensing rights, despite knowing absolutely nothing about the subject.  

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In the second episode of the UK Tech Weekly Podcast host Matt Egan discusses the Mobile World Congress (MWC) with producer Chris Martin before he jets off to Barcelona, including what device launches we are expecting from the likes of LG, Sony and Samsung. Acting editor at Macworld.co.uk David Price chats about the row between Apple and the FBI over encryption (14:50). Finally Scott Carey from Techworld.com discusses challenger banks (25:00) what they are, what the technology looks like and why you should care.  

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In this week's UK Tech Weekly Podcast host Matt Egan is joined by PC Advisor staff writer Chris Minasians chats about Facebook's new like buttons, the team has contracted smartphone fever from the Mobile World Conference in Barcelona and finally, acting editor of Macworld UK David Price, discusses Donald Trump boycotting Apple.  

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In this week's UK Tech Weekly Podcast host Matt Egan discusses VR with Lewis Painter, staff writer at PC Advisor and Chris Martin, consumer tech editor at PC advisor. Then Chris Minasians, staff writer at Macworld UK vents about how technology is destroying social interactions IRL (11:30), light stuff for your weekend listening pleasure! Finally (23:00) acting editor of Macworld UK David Price and the gang chat about paid-for-streaming advocate Kanye West doing a naughty and pirating music software.  

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This week host Matt Egan is joined by Ashleigh Allsopp, engagement editor of Macworld UK and physical bookshelf enthusiast to discuss eBooks and eReaders following the big Nook and Amazon Kindle news in the week (1:40). Producer Chris Martin chips in to talk about the death of the father of email, Ray Tomlinson, this week and the growth of workplace tools like Slack that are trying to reduce the amount we use email (12:30). Finally regular contributor and acting editor at Macworld UK David Price talks about Apple ransomware (24:00).  

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In this week's UK Tech Weekly Podcast host Matt Egan is joined by first time podder Tamlin Magee (1:50), online editor at ComputerworldUK.com, to discuss the UK tech implications of this year's Budget, including rural broadband and driverless cars. Then Christina Mercer, assistant online editor at Techworld.com, chats AlphaGo (10:00) and board games following the AI's historic win over world Go champion Lee Sedol. Later, resident Virtual Reality (VR) enthusiast and PCAdvisor.co.uk staff writer Lewis Painter discussed "the big three" VR headset release dates, pricing and features from HTC, Sony Playstation and Oculus Rift (19:00). Finally, UKTW Podcast regular David Price, acting editor at Macworld.co.uk chats about Apple's big upcoming event (28:45).  

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In this week's UK Tech Weekly Podcast host Matt Egan is joined by acting editor at Macworld.co.uk David Price to discuss this week's Apple event announcements, from the iPhone SE to the iPad Pro and iOS 9.3. Then first time podder and staff writer at Macworld.co.uk Henry Burrell wades in to discuss Facebook dropping its support for Blackberry and the future of the under-fire mobile phone maker (19:45). Finally, online editor at Techworld.com Scott Carey chats coding in schools following the BBC micro:bit news and how it differs from the Raspberry Pi (27:40).  

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Producer Chris dives in this week to discuss the HTC 10 release, and why it's difficult to get excited about good mobile phones. Then Techworld.com editor Charlotte Jee chats Facebook chatbots and other F8 news (12:30). Finally, editor at Digitalartsonline.co.uk Neil Bennett jumps in to discuss the new Amazon e-reader (31:00) Kindle Oasis and why everyone is kicking off about the price.  

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Host Matt Egan is joined this week by Henry Burrell, staff writer at Macworld UK to talk about the EU referendum website crashing Lewis Painter, staff writer at PC Advisor, jumps in to chat about Oculus Rift games and how immersive they are. Finally regular David Price comes on to talk about Apple's upcoming WWDC software developer conference and what we can (and cannot) expect.  

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This week Ashleigh Allsopp is simultaneously fascinated and worried by the UK launch of Amazon's Dash buttons, and discusses the many wonderful and not-so-wonderful things they enable you to buy on a drunken whim. Then David Price takes his turn to shine a spotlight on Apple's mysterious tax affairs (12:20) and tries to explain why the Irish government doesn't want to be given 13 billion euros. Finally a surprisingly riled-up Neil Bennett explains why women wearing headphones are not fair game for dimwitted pick-up artists (25:00), and ponders the social conventions surrounding the place of technology in each of our lives.  

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This week Henry Burrell is in the presenter chair and he has brought puns, sing-songs and tenuous Field of Dreams references. First up is producer Chris to discuss the Fitbit acquisition of fellow wearable maker Pebble and why owners are sad. Then online editor at Techworld Tamlin Magee is discussing the Met Police's decision to upload their body camera footage to the cloud and why this could be problematic (12:00). Finally, fellow online editor Scott Carey runs us through the Amazon Go news and how the retail giant is trying to pull off the technology behind its 'just walk out' shopping experience (24:00).  

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This week David Price is in the presenter chair for the jolliest tech podcast of the year. David is joined by Miriam Harris, staff writer at Digital Arts, to talk about the design trends set to shape 2017. Then online editor at Techworld Scott Carey runs through the hottest tech gifts this Christmas, including games consoles, VR, Amazon gadgets and Star Wars merch (14:30). Finally, staff writer at PC Advisor Dom Preston makes his UKTW debut to chat about the latest Star Wars movie, Rogue One, which includes spoilers (29:00). This is the last UK Tech Weekly podcast of the year. Thank you for listening and we will be back in 2017 to chat about the hottest tech topics all over again.  

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The first pod of 2017 explodes into view like your hangover on January 1st with host David Price probing the panel on its blurry eyed take on tech in the New Year. Ashleigh Macro, Engagement Editor of PC Advisor and Macworld UK returns to the pod to recap the expected and unexpected tech of 2016. Will Apple and Amazon reign supreme? Then Chris Martin, Consumer Tech Editor at PC Advisor, hot off the plane from CES in Las Vegas to discuss what was hot and what was really not at the largest tech show in the world. To top it off with some New Year optimism is pod debutant Tom MacAulay, Online Editor at Computerworld UK to let us know all the good (but mainly bad) things we can expect in warfare tech in the next decade.  

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Host Matt Egan clips us round the ear and tells us to listen up as we chat yet more tech and then some other stuff about tech. Consumer tech editor at PC Advisor Chris Martin lays down his definitive opinion after he went hands on with the Nintendo Switch this week, and why the company really should have had their star plumber ready in time for launch. Tamlin Magee, Online Editor at Computerworld UK then takes us through the odd goings on at Davos, and whether or not the elite can identify with what tech actually means to real working people. To round us up, Acting Macworld UK Editor David Price explains why app prices are going up in the UK for iOS users, and why it might - might - not be UKIP's fault. Sort of.  

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Gather round as three men spend 30 minutes talking about tech. Wait, what do you mean 'no thanks'?! Matt Egan shares the mic with David Price and Henry Burrell to thrash out why Apple deemed a press release adequate to announce the successor to 2014's iPad Air 2. There's also a slick new red iPhone, and a black OnePlus 3T. What's with the limited editions, eh? Or are they even limited? The gang also chat about the developer preview of Android O, out now while Android N is barely months old. Is it too early to say if it'll kick ass, and why do Google and Apple need such long public lead time with new OS builds?  

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Back with a bumper edition after the Easter break, as Henry Burrell takes Scott Carey, David Price and Dom Preston on a chat odyssey to discuss Facebook's F8 conference. Will chat bots ever be good and who uses QR codes? The gang then discusses Apple's out of character decision to brief journos on the Mac Pro and even admit they got it wrong. Finally we talk about Nintendo stopping production of the NES Classic and whether there's more affordable retro goodness around the corner.  

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Join host Henry Burrell in conversation with two editors, Karen Khan of Macworld UK in her debut pod along with pod regular Charlotte Jee of Techworld. We tackle the issues of privacy and self esteem, particularly in the young people that we are not, and ask who this product is for (because surely it will sell). Tech obviously plays a big part in the selfie phenomenon/epidemic. Second we discuss automation and how it is affecting the job market. Can a robot make an iPhone? Is Trump right about bringin' it all back home? What should politicians be doing to understand the technology involved? Thanks for listening, listener.  

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A classic edition of the pod as we hark back to the hallowed three topic format. Henry Burrell hosts David Price, Scott Carey and Chris Martin to ask just how Netflix got so popular. Will it sustain it though? Windows Phone is also pretty much actually dead but the funeral march is long. Other phone stuff includes the hallowed iPhone 8, the demise of Vertu and Nokia not really being Nokia. David then tells us why Google Glass is back, what it means for the enterprise, and why didn't they realise the first time round that it wasn't a consumer play?  

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We finally get the IoT acronym the pod has been waiting for as we discuss Bitcoin and 17th century Dutch finance. Charlotte Jee informs Henry Burrell, David Price and Scott Carey.

Scott then leads us down the winding road of the so-called platform wars, in a week when Google blocked the Amazon Echo Show from streaming YouTube. Is this a bump in the road or will services be cut from rival hardware?

And finally, led by David, the pod discusses its favourite tech of the year and what you might consider buying for friends and family for Christmas.

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Once more for 2017 as Henry Burrell, Karen Khan and Scott Carey bid farewell to this wonderful year (ahem) with musings on Apple's sexy new iMac Pro. Who is it for, how much is it and does this mean there is no Mac Pro in 2018?

We then tackle Netflix's Twitter shaming of its users and why Spotify got away with it earlier in the year. How comfortable are we all when we realise how much data companies really have on us?

In light of this, Apple bought Shazam - most likely for the data sets as much as the tech and the talent. What form will it take in Apple as another UK tech company is acquired?

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This week host Charlotte Jee breaks down open banking with Computerworld UK editor Scott Carey: what is it and why should we care?

Then audience development editor Christina Mercer explains why chip-maker Qualcomm has been fined nearly €1 billion and the EU's sustained attack on big tech (12:00)

Last up is senior staff writer at Tech Advisor Dom Preston to talk about Amazon's revolutionary concept Go store opening in Seattle and if this is really the future of shopping (20:00).

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David Price is in the host's chair this week, as the team talk about the latest hot tech topics. Tamlin Magee has got the drinks in - futuristic meal-replacement drinks called Soylent, which he forces everyone to try and which are apparently not people.

Then Dominic Preston talks us through the positive and extremely negative sides of Amazon's Black Friday activities, before Sean Bradley attempts to explain why Bitcoin is tanking and what the future holds for crypto currencies. Cheers!

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Two’s a crowd for this week’s games and Christmas pod with Consumer Tech Editor Henry Burrell and Games Editor Lewis Painter. Lewis lines up reviews of the awful Fallout 76 and the excellent online mode of Red Dead Redemption 2 – two polar opposites in how to make a decent online multiplayer game.

We also discuss smartwatches we’ve recently reviewed that left us feeling cold and why Apple is still king of the hill.

And to get into the festive vibe, interspersed throughout as we enter December are our top tech Christmas gift picks, both cheap and indulgent.

Everything we recommend is linked below:

Google Home Hub

Tile Bluetooth tracker

Red Dead Redemption 2 (PS4)

Super Smash Bros – Ultimate (Switch)

Pokémon: Let’s Go, Pikachu! (Switch)

Turtle Beach Elite Pro 2 + Superamp

Amazon Kindle Paperwhite

PlayStation Classic

PlayStation VR Starter Pack

The best budget smartphones

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This manuscript has been withdrawn by the Author.

Gram-negative bacteria possess an asymmetric outer membrane (OM) composed primarily of lipopolysaccharides (LPS) on the outer leaflet and phospholipids (PLs) on the inner leaflet. Loss of this asymmetry due to mutations in the lipopolysaccharide (LPS) biosynthesis or transport pathways causes externalization of PLs to the outer leaflet of the OM and leads to OM permeability defects. Here, we employed metabolic labeling to detect a compromised OM in intact bacteria. Phosphatidylcholine synthase (Pcs) expression in Escherichia coli allowed for incorporation of exogenous propargylcholine (PCho) into phosphatidyl(propargyl)choline (PPC) and for incorporation of exogenous 1-azidoethyl-choline (AECho) into phosphatidyl(azidoethyl)choline (AEPC) as confirmed by LC-MS analyses. A fluorescent copper-free click reagent poorly labeled AEPC in intact wild-type cells, but readily labeled AEPC from lysed cells. Fluorescence microscopy and flow cytometry analyses confirmed the absence of significant AEPC labeling from intact wild-type E. coli strains, and revealed significant AEPC labeling in an E. coli LPS transport mutant (lptD4213) and an LPS biosynthesis mutant (E. coli lpxC101). Our results suggest that metabolic PL labeling with AECho is a promising tool to detect a compromised bacterial OM, reveal aberrant PL externalization, and identify or characterize novel cell-active inhibitors of LPS biosynthesis or transport.

Inhibition of acid sphingomyelinase (ASM), a lysosomal enzyme that catalyzes the hydrolysis of sphingomyelin into ceramide and phosphorylcholine, may serve as an investigational tool or a therapeutic intervention to control many diseases. Specific ASM inhibitors are currently not sufficiently characterized. Here, we found that 1-aminodecylidene bis-phosphonic acid (ARC39) specifically and efficiently (>90%) inhibits both lysosomal and secretory ASM in vitro. Results from investigating sphingomyelin phosphodiesterase 1 (SMPD1/Smpd1) mRNA and ASM protein levels suggested that ARC39 directly inhibits ASM’s catalytic activity in cultured cells, a mechanism which differs from that of functional inhibitors of ASM (FIASMAs). We further provide evidence that ARC39 dose- and time-dependently inhibits lysosomal ASM in intact cells, and we show that ARC39 also reduces platelet- and ASMpromoted adhesion of tumor cells. The observed toxicity of ARC39 is low at concentrations relevant for ASM inhibition in vitro, and it does not strongly alter the lysosomal compartment or induce phospholipidosis in vitro. When applied intraperitoneally in vivo, even subtoxic high doses administered short-term induced sphingomyelin accumulation only locally in the peritoneal lavage without significant accumulation in plasma, liver, spleen or brain. These findings require further investigation with other possible chemical modifications. In conclusion, our results indicate that ARC39 potently and selectively inhibits ASM in vitro and highlight the need for developing compounds that can reach tissue concentrations sufficient for ASM inhibition in vivo.

Nutritional studies rely on various biological specimens for fatty acid (FA) determination, yet it is unclear how levels of serum non-esterified FA (NEFAs) correlate with other circulating lipid pools. Here, we used a high throughput method (< 4 min/sample) based on multisegment injection-non-aqueous-capillary electrophoresis–mass spectrometry (MSI-NACE-MS) to investigate whether specific serum NEFAs have utility as biomarkers of dietary fat intake in women. We first  identified circulating NEFAs correlated with long-term/habitual food intake among pregnant women with contrasting dietary patterns (n=50). Acute changes in serum NEFA trajectories were also studied in non-pregnant women (n=18) following high-dose (5 g/day) fish oil (FO) supplementation or isoenergetic sunflower oil placebo over 56 days. In the cross-sectional study, serum omega-3 (-3) FA correlated with self-reported total -3 daily intake, notably eicosapentaenoic acid (EPA) as its NEFA (r=0.46; p=0.001), whereas pentadecanoic acid was associated with full-fat dairy intake (r=0.43; p=0.002), outcomes consistent with results from  total FA serum hydrolysates. In the intervention cohort, serum -3 NEFAs increased 2.5-fold from baseline within 28 days following FO supplementation, and this increase was most pronounced for EPA (p=0.0004). Unlike for docosahexaenoic acid, circulating EPA as its NEFA also strongly correlated to EPA concentrations measured from erythrocyte phospholipid hydrolysates (r=0.66; p=4.6 x 10-10), and was better suited to detect dietary non-adherence. We conclude that MSI-NACE-MS offers a rapid method to quantify serum NEFAs and objectively monitor dietary fat intake in women that is complementary to diet records or food frequency questionnaires.

Ether lipids (ELs) are lipids characterized by the presence of either an ether linkage (alkyl lipids) or a vinyl ether linkage (i.e. plasmalogens [Pls]) at the sn1 position of the glycerol backbone and they are enriched in PUFAs at the sn2 position. In this review, we highlight that ELs have various biological functions, act as a reservoir for second messengers (such as PUFAs), and have roles in many diseases. Some of the biological effects of ELs may be associated with their ability to regulate ion channels that control excitation-contraction/secretion/mobility coupling and therefore cell physiology. These channels are embedded in lipid membranes, and lipids can regulate their activities directly or indirectly as second messengers or by incorporating into membranes. Interestingly, ELs and EL-derived PUFAs have been reported to play a key role in several pathologies, including neurological disorders, cardiovascular diseases, and cancers. Investigations leading to a better understanding of their mechanisms of action in pathologies have opened a new field in cancer research. In summary, newly identified lipid regulators of ion channels, such as ELs and PUFAs, may represent valuable targets to improve disease diagnosis and advance the development of new therapeutic strategies for managing a range of diseases and conditions.

Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) stratum corneum ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active, epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in stratum corneum ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered stratum corneum ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS. 

Oxidized low-density lipoprotein (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized phosphatidylcholine (oxPC) monoclonal antibody, was recovered in flow-through and electronegative LDL (LDL(-)) fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in LDL(-) fraction, present in patients with acute myocardial infarction (AMI) was three-fold higher than that observed in healthy subjects. Surprisingly, LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues were identified in apoB. The amount of oxPC adducts of apoB was higher in LDL(-) than in L1 fraction as determined using western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC monoclonal antibody. Majority of PC species was not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Niemann–Pick type C1 (NPC1) disease is a rare genetic condition in which the function of the lysosomal cholesterol transporter NPC1 protein is impaired. Consequently, sphingolipids and cholesterol accumulate in lysosomes of all tissues, triggering a cascade of pathological events that culminate in severe systemic and neurological symptoms. Lysosomal cholesterol accumulation is also a key-factor in the development of atherosclerosis and non-alcoholic steatohepatitis (NASH). In these two metabolic diseases, the administration of plant stanol esters has been shown to ameliorate cellular cholesterol accumulation and inflammation. Given the overlap of pathological mechanisms among atherosclerosis, NASH and NPC1 disease, we sought to investigate whether dietary supplementation with plant stanol esters improves the peripheral features of NPC1 disease. To this end, we used an NPC1 murine model featuring an Npc1 null allele (Npc1^nih), creating a dysfunctional NPC1 protein. Npc1^nih mice were fed a two or six percent plant stanol esters–enriched diet over the course of 5 weeks. During this period, hepatic and blood lipid and inflammatory profiles were assessed. Npc1^nih mice fed the plant stanol–enriched diet exhibited lower hepatic cholesterol accumulation, damage and inflammation than regular chow–fed Npc1^nih mice. Moreover, plant stanol consumption shifted circulating T-cells and monocytes in particular towards an anti-inflammatory profile. Overall, these effects were stronger following dietary supplementation with 6% stanols, suggesting a dose-dependent effect. The findings of our study highlight the potential use of plant stanols as an affordable complementary means to ameliorate disorders in hepatic and blood lipid metabolism and reduce inflammation in NPC1 disease.

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity?  What is the effect of statin treatment? Obese, hypertriglyceridemic, hypercholesterolemic males (n=12; Lp(a) <10 mg/dL) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids (lysophosphatidylcholine (LPC); lysophosphatidylinositol (LPI); lyso-platelet activating factor (LPC(O)); 9,0.2 and 0.14 mol/mol apoB respectively; all p<0.001 versus LDL1-4), suggesting  elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5 - 3 mol/mol apoB; 3 - 7 mmol/mol phosphatidylcholine) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.