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Obligate intracellular protozoan parasite, Leishmania donovani, causative agent of visceral leishmaniasis, led to impaired macrophage functions. It is well documented that many of these changes were induced by parasite-mediated reduction in macrophage cholesterol content. Leishmania-mediated alteration in the other lipids has not been explored in detail yet. Here, we found that the expression of key cholesterol biosynthetic genes and total cellular cholesterol were reduced during L. donovani infection. Further, we have also identified that this reduction in the cholesterol led to increased membrane fluidity and inhibition of antigen-presenting potential of macrophages. In addition to this, we studied the relative changes in different lipids in THP-1-derived macrophages during L. donovani infection through liquid chromatography-mass spectrometry. We found that Sphingomyelin (16:0) and ceramide (20:1, 26:0 and 26:1) were significantly reduced in infected macrophages. We further observed that the majority of different sub-classes of phospholipids were downregulated significantly. Overall ratio of phosphatidylcholine versus phosphotidylethanolamine was decreased which indicated the compensatory mechanism of cell in response to cholesterol reduction. The observed Leishmania-mediated alteration in macrophage-lipidome provided the novel insights into mechanism of host-pathogen interactions., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial., Methods: Among 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT., Results: In the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (-0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94-0.99) for a -7 mg/dL (-0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01-1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01-1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96-1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91-1.15) in the PROMINENT trial., Conclusions: Absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BGN reports consultancies or talks sponsored by AstraZeneca, Sanofi, Regeneron, Akcea, Amgen, Amarin, Kowa, Denka, Novartis, Novo Nordisk, Esperion, Silence Therapeutics, Abbott, Mankind, Lilly, and Arrowhead. TD reports a consultancy by Novo Nordisk. AL reports a talk sponsored by Amarin and a consultancy by Novartis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Chios Mastiha essential oil (CMO) is a natural product extracted from the resin of Mastiha, possessing antioxidant, anti-microbial, anti-ulcer, anti-neoplastic, and cholesterol-lowering capabilities in vitro, and its hypolipidemic effect was confirmed in animal studies. Yet, there are no randomized, placebo-controlled clinical studies in the literature regarding CMO's hypolipidemic effects in humans. A prospective, randomized, placebo-controlled study was designed to study the hypolipidemic effect of CMO capsules on healthy volunteers with elevated cholesterol., Methods: 192 healthy volunteers were screened and 160 of them with total cholesterol> 200 mg/dl participated in the study. They were randomized with a 2:1 ratio of receiving CMO capsules (200 mg mastiha-oil/capsule) and placebo for 8 weeks respectively. 113 patients received CMO and 47 were randomized in the control group, and all of them completed the follow-up period., Results: After 8 weeks of CMO administration, total and LDL cholesterol were significantly lower in the CMO compared to the placebo group 215.2 ± 27.5 vs 237.0 ± 27.9 mg/dl (p < 0.001) and 135.0 ± 26.1 vs 153.0 ± 23.3 mg/dl (p < 0.001) respectively. No gastrointestinal adverse events or liver or renal toxicity were reported. Additionally, in the CMO group total cholesterol was significantly decreased by 20.6 mg/dl (9%), LDL by 18.1 mg/dl (12%), triglycerides by 21.8 mg/dl (15%), and glucose by 4.6 mg/dl (5%) and HDL was increased by 2.4 mg/dl (5%), compared to their baseline values., Conclusion: The MASTIHA-OIL study showed the efficacy and safety of CMO in reduction of total and LDL cholesterol after 8 weeks of administration in healthy volunteers with elevated cholesterol levels., (Copyright © 2023 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Accurate intracellular cholesterol traffic plays crucial roles. Niemann Pick type C (NPC) proteins NPC1 and NPC2, are two lysosomal cholesterol transporters that mediate the cholesterol exit from lysosomes. However, other proteins involved in this process remain poorly defined. Here, we find that the previously unannotated protein TMEM241 is required for cholesterol egressing from lysosomes through amphotericin B-based genome-wide CRISPR-Cas9 KO screening. Ablation of TMEM241 caused impaired sorting of NPC2, a protein utilizes the mannose-6-phosphate (M6P) modification for lysosomal targeting, resulting in cholesterol accumulation in the lysosomes. TMEM241 is a member of solute transporters 35 nucleotide sugar transporters family and localizes on the cis-Golgi network. Our data indicate that TMEM241 transports UDP-N-acetylglucosamine (UDP-GlcNAc) into Golgi lumen and UDP-GlcNAc is used for the M6P modification of proteins including NPC2. Furthermore, Tmem241-deficient mice display cholesterol accumulation in pulmonary cells and behave pulmonary injury and hypokinesia. Taken together, we demonstrate that TMEM241 is a Golgi-localized UDP-GlcNAc transporter and loss of TMEM241 causes cholesterol accumulation in lysosomes because of the impaired M6P-dependent lysosomal targeting of NPC2., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Reprogramming lipid metabolic pathways is a critical feature of activating immune responses to infection. However, how these reconfigurations occur is poorly understood. Our previous screen to identify cellular deubiquitylases (DUBs) activated during influenza virus infection revealed Usp25 as a prominent hit. Here, we show that Usp25-deleted human lung epithelial A549 cells display a >10-fold increase in pathogenic influenza virus production, which was rescued upon reconstitution with the wild type but not the catalytically deficient (C178S) variant. Proteomic analysis of Usp25 interactors revealed a strong association with Erlin1/2, which we confirmed as its substrate. Newly synthesized Erlin1/2 were degraded in Usp25 -/- or Usp25 C178S cells, activating Srebp2, with increased cholesterol flux and attenuated TLR3-dependent responses. Our study therefore defines the function of a deubiquitylase that serves to restrict a range of viruses by reprogramming lipid biosynthetic flux to install appropriate inflammatory responses., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Metabolic alterations are often found in patients with clinical psychosis early in the course of the disorder. Psychotic-like experiences are observed in the general population, but it is unclear whether these are associated with markers of metabolism., Methods: A population-based cohort of 1890 individuals (mean age 58.0 years; 56.3% women) was included. Metabolic parameters were measured by body-mass index (BMI), concentrations of low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C), total cholesterol, triglycerides, and fasting glucose and insulin in blood. Frequency and distress ratings of psychotic-like experiences from the positive symptom dimension of the Community Assessment of Psychic Experience questionnaire were assessed. Cross-sectional associations were analysed using linear regression analyses., Results: Higher BMI was associated with higher frequency of psychotic-like experiences (adjusted mean difference: 0.04, 95% CI 0.02-0.06) and more distress (adjusted mean difference: 0.02, 95% CI 0.01-0.03). Lower LDL-C was associated with more psychotic-like experiences (adjusted mean difference: -0.23, 95% CI -0.40 to -0.06). When restricting the sample to those not using lipid-lowering medication, the results of BMI and LDL-C remained and an association between lower HDL-C and higher frequency of psychotic-like experiences was found (adjusted mean difference: -0.37, 95% CI -0.69 to -0.05). We observed no significant associations between cholesterol, triglycerides, glucose, insulin or homeostatic model assessment and psychotic-like experiences., Conclusions: In a population-based sample of middle-aged and elderly individuals, higher BMI and lower LDL-C were associated with psychotic-like experiences. This suggests that metabolic markers are associated with psychotic-like experiences across the vulnerability spectrum., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Differences between men and women in lipids and lipoproteins are observed in distribution and trajectory from infancy to adulthood in the general population. However, these differences are more pronounced in hereditary lipid disorders such as familial hypercholesterolemia (FH) when absolute cholesterol levels are higher from birth onwards. In the early life course, girls compared to boys have higher low-density lipoprotein cholesterol (LDL-C) levels and total cholesterol, while high-density lipoprotein cholesterol (HDL-C) levels are similar. In early adulthood to middle-age, women have lower LDL-C and higher HDL-C levels, as LDL-C levels increase and HDLC levels decrease in men. In the elderly, all lipids - total cholesterol, LDL-C, HDL-C and triglyceride levels decrease but are more pronounced in men. Lipid levels are also affected by specific transitions in girls/women such as the menstrual cycle, pregnancy, breastfeeding and menopause. Lipid levels fluctuate during the menstrual cycle. During pregnancy a physiological increase of LDL-C and even a larger increase in triglyceride levels are observed. Pregnancy has a double impact on LDL-C accumulation in women with FH as they have to stop statins, and the absolute increase in LDL-C is higher than in women without FH. In the menopausal transition, women develop a more adverse lipid profile. Therefore, it is important to take into account both sex and the life course when assessing a lipid profile., Competing Interests: Declaration of competing interest Potential conflicts of interest outside the submitted work: KBH has received research grants and/or personal fees from Mills, Amgen and Sanofi; JRVL declares to have received research grants from Amryt and Novartis., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background and Aims: During fat tolerance tests, plasma triglycerides increase while high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and intermediate-density lipoprotein (IDL) cholesterol decrease. However, it is unknown whether triglyceride content increases and cholesterol content decreases in HDL and LDL + IDL fractions following normal meals in the general population. Therefore, we tested the hypothesis that triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions following normal meals., Methods: In this cross-sectional study, we included 25,656 individuals aged 20-100 years, all without lipid-lowering therapy at examination and selected for metabolomic profiling from the Copenhagen General Population Study. Triglyceride and cholesterol content of 14 lipoprotein fractions weas measured using nuclear magnetic resonance (NMR) spectroscopy. Time since last meal was recorded by the examiner immediately before blood sampling., Results: Following normal meals in age and sex-adjusted analyses and when compared with fasting levels, plasma triglycerides were higher for up to 5-6 h, and triglyceride content was higher for up to 6-7 h in HDL fractions, for up to 6-7 h in LDL + IDL fractions, and for up to 5-6 h in very-low-density lipoprotein (VLDL) fractions. Further, plasma cholesterol was lower for up to 2-3 h, and cholesterol content was lower for up to 0-1 h in HDL fractions and for up to 4-5 h in LDL + IDL fractions, while cholesterol content was higher for up to 4-5 h in VLDL fractions., Conclusions: Following normal meals, triglyceride content increases while cholesterol content decreases in HDL and LDL + IDL fractions., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The relationship between lipid metabolism and pneumonia in under-five children remains unclear. The aim of the study was to explore the association of several lipids, lipoproteins and apolipoproteins with the risk of childhood pneumonia, and to initially reveal the mechanisms involved., Methods: There were 1000 children with confirmed severe pneumonia and 1000 healthy controls (18-59 months old) in the study. Serum levels of several lipids, lipoproteins and apolipoproteins were measured. The occurrence of hypoxaemia and serum level of C-reactive protein were recorded. Multivariate logistic regression and spearman correlation analysis were adopted to assess the correlation between these variables to achieve the research objective., Results: First, higher triglycerides, total cholesterol, LDL cholesterol, VLDL cholesterol and apolipoprotein B levels were associated with the elevated risk of severe pneumonia (OR: 1.407, 95%CI: 1.336∼1.480; OR: 1.947, 95%CI: 1.741∼2.175; OR: 1.153, 95%CI: 1.116∼1.189; OR: 1.310, 95%CI: 1.222∼1.404; OR: 1.075, 95%CI: 1.003∼1.151). Higher HDL cholesterol and apolipoprotein A1 levels were associated with a decreased risk of the disease (OR: 0.903, 95%CI: 0.873∼0.933; OR: 0.921, 95%CI: 0.891∼0.952). Second, higher triglycerides level was associated with an increased risk of hypoxemia in these children (OR: 1.142, 95%CI: 1.072∼1.215). Third, serum HDL cholesterol level was linearly associated with C-reactive protein level in these children (ρ = -0.343, P < 0.001)., Conclusion: Abnormal levels of several lipids, lipoproteins and apolipoproteins were related to severe childhood pneumonia. The findings that triglycerides and HDL cholesterol were respectively implicated in hypoxaemia and inflammation might partly explain the mechanisms linking lipid metabolism to severe pneumonia., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

Plasma membrane segregation into various nanoscale membrane domains is driven by distinct interactions between diverse lipids and proteins. Among them, liquid-ordered ( L o ) membrane domains are defined as "lipid rafts" and liquid-disordered ( L d ). Meanwhile, confocal fluorescence microscopy experiments of HeLa and 293T cell lines indicated that membrane cholesterol depletion could significantly alter the transmembrane potential of cells. Considering differences in the cholesterol content between L o / L d ). Meanwhile, confocal fluorescence microscopy experiments of HeLa and 293T cell lines indicated that membrane cholesterol depletion could significantly alter the transmembrane potential of cells. Considering differences in the cholesterol content between L o and L d membrane domains, our confocal fluorescence microscopy experiments are consistent with our all-atom MD simulations. In short, membrane domain anti-registration induces local membrane asymmetry and, thus, an intrinsic transmembrane potential.

The activity of neuronal Kv7.2/Kv7.3 channels is critically dependent on PIP 2 and finely modulated by cholesterol. Here, we report the crosstalk between cholesterol and PIP 2 in the regulation of Kv7.2/Kv7.3 channels. Our results show that currents passing through Kv7.2/Kv7.3 channels in cholesterol-depleted cells, by acute application of methyl-β-cyclodextrin (MβCD), were less sensitive to PIP 2 dephosphorylation strategies than those of control cells, suggesting that cholesterol depletion enhances the Kv7.2/Kv7.3-PIP 2 interaction. In contrast, the sensitivity of Kv7.2/Kv7.3 channels to acute membrane cholesterol depletion by MβCD was not altered in mutant channels with different apparent affinities for PIP 2 ., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Cholesterol reduction is considered a mechanism through which cholesterol-lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)- and high (HDL)-density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown., Methods: We conducted a prospective study of 1553 Black and 5071 White cancer-free men attending visit 1 (1987-1989) of the Atherosclerosis Risk in Communities Study. A total of 885 incident prostate cancer cases were ascertained through 2015, and 128 prostate cancer deaths through 2018. We estimated multivariable-adjusted hazard ratios (HRs) of total and fatal prostate cancer per 1-standard deviation increments and for tertiles (T1-T3) of time-updated lipid biomarkers overall and in Black and White men., Results: Greater total cholesterol concentration (HR per-1 SD = 1.25; 95% CI = 1.00-1.58) and LDL cholesterol (HR per-1 SD = 1.26; 95% CI = 0.99-1.60) were associated with higher fatal prostate cancer risk in White men only. Apolipoprotein B was nonlinearly associated with fatal prostate cancer overall (T2 vs. T1: HR = 1.66; 95% CI = 1.05-2.64) and in Black men (HR = 3.59; 95% CI = 1.53-8.40) but not White men (HR = 1.13; 95% CI = 0.65-1.97). Tests for interaction by race were not statistically significant., Conclusions: These findings may improve the understanding of lipid metabolism in prostate carcinogenesis by disease aggressiveness, and by race while emphasizing the importance of cholesterol control., (© 2023 Wiley Periodicals LLC.)

Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults and is highly resistant to chemo- and radiotherapies. GBM has been associated with alterations in lipid contents, but lipid metabolism reprogramming in tumor cells is not fully elucidated. One of the key hurdles is to localize the lipid species that are correlated with tumor growth and invasion. A better understanding of the localization of abnormal lipid metabolism and its vulnerabilities may open up to novel therapeutic approaches. Here, we use time-of-flight secondary ion mass spectrometry (ToF-SIMS) to spatially probe the lipid composition in a GBM biopsy from two regions with different histopathologies: one region with most cells of uniform size and shape, the homogeneous part, and the other with cells showing a great variation in size and shape, the heterogeneous part. Our results reveal elevated levels of cholesterol, diacylglycerols, and some phosphatidylethanolamine in the homogeneous part, while the heterogeneous part was dominated by a variety of fatty acids, phosphatidylcholine, and phosphatidylinositol species. We also observed a high expression of cholesterol in the homogeneous tumor region to be associated with large cells but not with macrophages. Our findings suggest that ToF-SIMS can distinguish in lipid distribution between parts within a human GBM tumor, which can be linked to different molecular mechanisms.

The lipid profile is important in the risk assessment for cardiovascular disease. The lipid profile includes total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides (TGs) and low-density lipoprotein (LDL)-cholesterol (LDL-C). LDL-C has traditionally been calculated using the Friedewald equation (invalid with TGs greater than 4.5 mmol/L and is based on the assumption that the ratio of TG to cholesterol in very- low-density lipoprotein (VLDL) is 5 when measured in mg /dL). LDL-C can be quantified with a reference method, beta-quantification involving ultracentrifugation and this is unsuitable for routine use. Direct measurement of LDL-C was expected to provide a solution with high TGs. However, this has some challenges because of a lack of standardisation between the reagents and assays from different manufacturers as well as the additional costs. Furthermore, mild hypertriglyceridaemia also distorts direct LDL-C measurements. With the limitations of the Friedewald equation, alternatives have been derived. Newer equations include the Sampson-National Institutes of Health (NIH) equation 2 and the Martin-Hopkins equation. The Sampson-NIH2 equation was derived using beta-quantification in a population with high TG and multiple least squares regression to calculate VLDL-C, using TGs and non-HDL-C as independent variables. These data were used in a second equation to calculate LDL-C. The Sampson-NIH2 equation can be used with TGs up to 9 mmol/L. The Martin-Hopkins equation uses a 180 cell stratification of TG/non-HDL-C to determine the TG:VLDL-C ratio and can be used with TGs up to 4.5 mmol/L. Recently, an extended Martin-Hopkins equation has become available for TGs up to 9.04 mmol/L.This article discusses the best practice approach to calculating LDL-C based on the available evidence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Despite recent large-scale discordance studies showing definitively that atherosclerotic cardiovascular disease (ASCVD) risk correlates better with apolipoprotein B (apoB) than with low-density lipoprotein cholesterol (LDL-C), the latter remains the recommended metric for guiding lipid-lowering treatment decisions in the United States. A major barrier to change, in this regard, is the lack of guideline-recommended apoB treatment targets. We developed a simple method to "translate" apoB values into population-equivalent LDL-C units, allowing apoB-based treatment decisions to be made using LDL-C targets., Methods: Sequentially collected, population-based samples underwent standard lipid panel analysis and apoB testing by immunoassay. Those with triglycerides greater than 1000 mg/dl were excluded, leaving a study cohort of 15 153 individuals., Results: Linear regression of calculated LDL-C values against percentile-equivalent apoB values yielded an equation to convert apoB into percentile-equivalent LDL-C units: [LDL-C equivalents = 1.38(apoB) - 29] (R2 = 0.999). The extent of discordance between LDL-C and apoB was examined in subgroups with similar LDL-C, ranging from very low (55-70 mg/dL) to very high (175-190 mg/dL). Among individuals with very low LDL-C, 40% had discordantly higher apoB, indicating higher ASCVD risk. Of those with very high LDL-C, 49% had discordantly lower apoB. Across the range, a minority of patients (25%-40%) had concordant levels of apoB, confirming that discordance between these biomarkers is highly prevalent. Similar results were found in discordance analysis between apoB and non-high-density lipoprotein cholesterol (HDL-C)., Conclusions: Providing visibility to discrepancies among LDL-C, non-HDL-C, and apoB should help to facilitate more rapid and widespread adoption of apoB for managing ASCVD risk., (Published by Oxford University Press on behalf of American Association for Clinical Chemistry 2022.)

Introduction: This cross-sectional study explored whether nutrition, body composition, and physical activity energy expenditure (PAΕΝ) have a differential impact on lipidemic blood profiles among young females with different blood cholesterol concentrations., Methods: One hundred thirty-five young female students (N = 135) were allocated into three groups according to their blood cholesterol concentrations (Chol): (A) Normal [NL; Chol: < 200 mg·dL -1 ; n = 56 Age: 21.4 ± 2.6 yrs, Body Mass Index (BMI): 22.1 ± 2.0 kg·m -2 ], (B) Borderline (BL; Chol: ≥200 mg·dL -1 and <240 mg·dL -1 ; n = 44 Age: 21.6 ± 2.5 yrs, BMI: 24.2 ± 3.1 kg·m -2 ) and (C) High level (HL; Chol: ≥240 mg·dL -1 ; n = 35 Age: 22.5 ± 2.4 yrs, BMI: 28.9 ± 2.1 kg·m -2 ). Body composition [bioelectrical impedance analysis including lean body mass (LBM) and body fat mass], nutritional intake (recall questionnaire), daily physical activity energy expenditure through activity trackers and resting blood lipids concentrations were evaluated., Results: Multiple linear regression analyses revealed that in the NL group, lean mass, daily PAΕΝ and daily energy balance were the determinant parameters of blood lipidemic profiles (B: -0.815 to 0.700). In the BL group, nutrition, body composition and daily physical activity energy expenditure exhibited similar impacts (B: -0.440 to 0.478). In the HL group, nutritional intake and body fat mass determined blood lipidemic profile (B: -0.740 to 0.725)., Conclusion: Nutrition, body composition and daily PAΕΝ impact on blood lipids concentration is not universal among young females. In NL females, PAEN, energy expenditure and LBM are the strongest determinants of blood lipids, while in HL females, nutritional intake and body fat mass are. As PAΕΝ increases, the importance of nutrition and body fat decreases, and vice versa., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Background: This systematic review and dose-response meta-analysis of published randomized controlled trials (RCTs) was conducted to determine the effectiveness of camelina oil supplementation (COS) on lipid profiles and glycemic indices., Methods: Relevant RCTs were selected by searching the ISI Web of Science, PubMed, and Scopus databases up to July 1, 2022. RTCs with an intervention duration of less than 2 weeks, without a placebo group, and those that used COS in combination with another supplement were excluded. Weighted mean differences and 95% confidence intervals were pooled by applying a random-effects model, while validated methods examined sensitivity analyses, heterogeneity, and publication bias., Results: Seven eligible RCTs, including 428 individuals, were selected. The pooled analysis revealed that COS significantly improved total cholesterol in studies lasting more than 8 weeks and utilizing dosages lower than 30 g/d compared to the placebo group. The results of fractional polynomial modeling indicated that there were nonlinear dose-response relations between the dose of COS and absolute mean differences in low-density cholesterol, high-density cholesterol, and total cholesterol, but not triglycerides. It appears that the greatest effect of COS oil occurs at the dosage of 20 g/day., Conclusion: The present meta-analysis indicates that COS may reduce cardiovascular disease risk by improving lipid profile markers. Based on the results of this study, COS at dosages lower than 30 g/d may be a beneficial nonpharmacological strategy for lipid control. Further RCTs with longer COS durations are warranted to expand on these results., (© 2022. The Author(s).)

Small residue-mediated interhelical packing is ubiquitous in helical membrane proteins: however, the lipid dependence of its stability remains unclear. We previously demonstrated that the introduction of a GXXXG sequence in the middle of de novo-designed (AALALAA) 3 helices (AALALAA AGLALGA AALALAA) facilitated their dimerization, which was abolished by cholesterol. Here single-pair FRET measurements revealed that a longer GXXXGXXXG segment (AALALAA A GLALGA AAGALAA) promoted helix dimerization in POPC/cholesterol bilayers, but not without cholesterol. The predicted dimer structures and degrees of helix packing suggested that helix dimers with small (∼10°) and large (∼55°) crossing angles were only stabilized in POPC and POPC/cholesterol membranes, respectively. A steric hindrance in the dimer interface and the large flexibility of helices prevented the formation of stable dimers. Therefore, amino acid sequences and lipid compositions distinctively constrain stable dimer structures in membranes., (© 2022 Wiley-VCH GmbH.)

Purpose: There is a growing body of evidence suggesting a decisive involvement of the human lipid metabolism in cancer development. However, clinical data on the association between blood triglyceride or cholesterol levels including the cholesterol transporters high-density and low-density lipoproteins (LDL, HDL) and cancer incidence have remained inconclusive. Here, we investigated the association between blood triglyceride as well as total, LDL and HDL cholesterol levels and cancer among outpatients from Germany., Methods: 61,936 patients with available blood lipid values were identified from the IQVIA Disease Analyzer database and followed up between 2005 and 2019. Multivariable logistic regression models were used to study the association between lipid values and cancer., Results: The probability of cancer was significantly lower among patients with elevated total cholesterol concentrations and higher in patients with decreased HDL serum levels. In contrast, serum concentrations of LDL and triglycerides had no impact on cancer risk. In cancer site-stratified analyses, we observed a trend towards higher rates of cancers from digestive organs, breast, skin cancer, urinary tract and cancers from lymphoid and hematopoietic tissue in patients with HDL values < 35 mg/dl, while a negative association between total cholesterol > 250 mg/dl and respiratory organ as well as urinary tract cancers was observed., Conclusion: Our data strongly support the hypothesis that serum-specific lipid profiles are positively associated with cancer., (© 2021. The Author(s).)

Objectives: Cholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. We evaluate the associations of CLC with coronary atherosclerosis presence, burden and cardiovascular risk in patients with rheumatoid arthritis (RA)., Methods: Coronary atherosclerosis (any, high-risk low-attenuation plaque and obstructive plaque) was evaluated with CT angiography in 141 patients. Participants were prospectively followed for 6.0±2.4 years and cardiovascular events including cardiac death, myocardial infarction, unstable angina, stroke, claudication, revascularisation and hospitalised heart failure were recorded. CLC was quantified as intracellular cholesterol in human macrophages after incubation with patient serum., Results: CLC was not linked to overall plaque presence or burden after adjustments for atherosclerotic cardiovascular disease (ASCVD) score, statin use and low-density lipoprotein cholesterol. However, CLC associated with presence and numbers of any, low-attenuation and obstructive plaques exclusively in biologic disease-modifying antirheumatic drugs (bDMARD) non-users (p for interaction ≤0.018). CLC associated with cardiovascular event risk overall after adjustments for ASCVD and number of segments with plaque (HR=1.76 (95% CI 1.16 to 2.67) per 1 SD increase in CLC, p=0.008). Additionally, bDMARD use modified the impact of CLC on event risk; CLC associated with events in bDMARD non-users (HR=2.52 (95% CI 1.36 to 4.65) per 1SD increase in CLC, p=0.003) but not users., Conclusion: CLC was linked to long-term cardiovascular event risk in RA and associated with high-risk low attenuation and obstructive coronary plaque presence and burden in bDMARD non-users. Its prospective validation as a predictive biomarker may be, therefore, warranted., Competing Interests: Competing interests: GAK has received consulting and speaker fees from Sanofi-Genzyme-Regeneron, Bristol-Meyer-Squibb and Janssen (less than $10 000 USD each). MJB has received consulting and speaker fees from Pfizer (less than $10 000 USD). BP, SRO, MP, EH, MPA, FZ and NR have nothing to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Physiological changes that occur during pregnancy can influence serum lipid levels and laboratory tests for renal function. Therefore, we established consecutive and reliable RIs for serum lipid and renal function indices for pregnant women in China throughout the entirety of pregnancy., Methods: We included 120 healthy pregnant women who underwent a naturally conceived and uncomplicated pregnancy and delivered a healthy singleton neonate. Serum samples were collected at ten time points (pre-pregnancy, gestational age ≤ 8 weeks (W), 8 W +1 to 12 W, 12 W +1 to 16 W, 16 W +1 to 20 W, 20 W +1 to 24 W, 24 W +1 to 28 W, 28 W +1 to 32 W, 32 W +1 to 36 W, and 36 W +1 to 40 W) and analyzed for ten common serum lipid and renal function analytes. RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine recommendations and compared with the established RIs for healthy adult women., Results: During pregnancy, we observed significant increases in total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein-A1 (Apo-A1), apolipoprotein-B (Apo-B), cystatin C (Cys-C), and estimated glomerular filtration rate (eGFR). We also observed clear reductions in urea, creatinine (Crea), and uric acid (UA). Compared with the previously established RIs, the most significant misclassifications were recorded for TG, Apo-A1, Crea, and eGFR., Conclusions: We successfully described key changes in serum lipid levels and renal function indices throughout pregnancy. It is important to establish RIs for blood indices in women undergoing normal pregnancies during different period of pregnancy to avoid the misdiagnosis of disease states., (© 2022. The Author(s).)

The epidemiologic literature on associations between urinary phenol concentrations and lipid profiles during pregnancy is limited. We examined whether urinary concentrations of phenol and phenol replacement biomarkers were associated with serum lipid levels among pregnant women. This cross-sectional study included 175 women attending the Massachusetts General Hospital Fertility Center who enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 and had data available on urinary phenol biomarkers and serum lipids during pregnancy. We used linear regression models to assess the relationship between groups of urinary phenol and phenol replacement biomarkers and serum lipid levels [total cholesterol, high density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, and triglycerides], while adjusting for age at sample collection, pre-pregnancy BMI, education, race, infertility diagnosis, cycle type, number of fetuses, trimester and specific gravity. In adjusted models, pregnant women with urinary propylparaben concentrations in the highest tertile had 10% [22 (95% CI = 5, 40) mg/dL], 12% [19 (95% CI = 2, 36) mg/dL] and 16% [19 (95% CI = 3, 35) mg/dL] higher mean total, non-HDL and LDL cholesterol, respectively, compared to women with concentrations in the lowest tertile. Similar elevations were observed for urinary bisphenol A concentrations. Urinary bisphenol S, benzophenone-3, triclosan, methylparaben, ethylparaben, and butylparaben were unrelated to serum lipids. Among pregnant women, urinary concentrations of bisphenol A and propylparaben were associated with higher serum levels of total, non-HDL and LDL cholesterol., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aim: The impact of 17β-estradiol plus norethisterone acetate administration on serum lipids in women is controversial as previously published studies have produced conflicting results. Thus, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to investigate the effects of 17β-estradiol plus norethisterone acetate therapy on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in females., Methods: We searched the PubMed/MEDLINE, Scopus, Embase, and Web of Science databases for relevant trials published in English until 15 July 2021. The weighted mean difference (WMD) and 95% confidence intervals (CIs) were calculated using a random-effects model (the DerSimonian and Laird methods)., Results: A total of 32 RCTs were included in the final analysis. Treatment with 17β-estradiol plus norethisterone acetate significantly decreased LDL-C (WMD: -13.49 mg/dL, 95% CI: -16.46 to -10.52; P < 0.001), HDL-C (WMD: -3.57 mg/dL, 95% CI: -5.56 to -1.58; P < 0.001), TC (WMD: -19.33 mg/dL, 95% CI: -24.14 to -14.52; P < 0.001), and TG (WMD: -10.86 mg/dL, 95% CI: -16.06 to -5.13; P < 0.001) levels in females. The non-linear dose-response meta-analysis revealed a negative correlation between HDL-C levels and increased treatment periods (P ˂ 0.001)., Conclusion: Evidence to date suggests that the administration of 17β-estradiol plus norethisterone acetate in females reduces LDL-C, HDL-C, TC, and TG concentrations. Future investigations should clarify whether the reduction in HDL-C following the administration of 17β-estradiol plus norethisterone acetate is clinically significant and poses any risks to the subjects who receive this treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Maternal lipid levels in early pregnancy are associated with maternal health and foetal growth. It is however unclear if maternal lipids in early pregnancy can be used to predict childhood lipid levels. The aim of this study is to assess the association between maternal and offspring childhood lipid levels, and to investigate the influence of maternal BMI and diet on these associations., Methods: This study included 2692 women participating in the Generation R study, an ongoing population-based prospective cohort study from early life onwards. Women with an expected delivery date between 2002 and 2006 living in Rotterdam, the Netherlands were included. Total cholesterol, triglycerides and high-density lipoprotein cholesterol (HDL-c) were measured in early pregnancy (median 13.2 weeks [90% range 10.6; 17.1]). Low-density lipoprotein cholesterol (LDL-c), remnant cholesterol and non-HDL-c were calculated. Corresponding lipid measurements were determined in 2692 children at the age of 6 (median 6.0 years [90% range 5.7; 7.5]) and 1673 children 10 years (median 9.7 years [90% range 9.5; 10.3]). Multivariate linear regression analysis was used to examine the association between maternal lipid levels in early pregnancy and the corresponding childhood lipid measurements at the ages of 6 and 10 years while adjusting for confounders., Results: Maternal lipid levels in early pregnancy are positively associated with corresponding childhood lipid levels 6 and 10 years after pregnancy, independent of maternal body mass index and diet., Conclusions: Maternal lipid levels in early pregnancy may provide an insight to the lipid profile of children years later. Gestational lipid levels may therefore be used as an early predictor of children's long-term health. Monitoring of these gestational lipid levels may give a window-of-opportunity to start early interventions to decrease offspring's lipid levels and possibly diminish their cardiovascular risk later in life. Future studies are warranted to investigate the genetic contribution on maternal lipid levels in pregnancy and lipid levels of their offspring years later., (© 2022. The Author(s).)

Objective: To evaluate the consistency of blood lipid test result under different storage conditions., Methods: Blood samples from 140 subjects were collected, centrifuged and were divided into five aliquots. One aliquot was used to determine serum total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C) and low density lipoprotein cholesterol(LDL-C) immediately, and the other four parts were stored at 4 ℃ for 4 h, 24 h, and frozen at-20 ℃ and-80 ℃ for 30 d, respectively, for the further measurement., Results: Immediate 0 h detection was compared with 4 ℃ for 4 h and 24 h, -20 ℃and-80 ℃ for 30 d: The difference Bland-Altman method was used to analyze TC and LDL-C data, and the mean TC difference values was 0.00, 0.00, 0.07 and 0.03 mmol/L, respectively. LDL-C difference value was-0.02, -0.04, -0.02 and-0.07 mmol/L, respectively, and 95% of the points were within the clinically acceptable conformance threshold. Ratio Bland-Altman method was used to analyze TG and HDL-C data. The mean TG ratios was 1.01, 1.00, 1.05, 1.05, and the mean HDL-C was 1.01, 1.03, 1.05 and 1.03, respectively. Ninety-five percent of the points were within the clinically acceptable consistency boundary. According to the 2021 Interlaboratory Quality Evaluation Standard of Clinical Laboratory Center of National Health Commission, the Bland-Altman analysis showed good consistency between the test result of different blood samples under different storage conditions and the immediate test result., Conclusion: In large population epidemiological studies, the results of TC, LDL-C, HDL-C and TG in sera being refrigerated at 4 ℃ for 4 h and 24 h, and frozen at-20 ℃ and-80 ℃ for 30 d, were consistent with the result of immediate detection.

Background: Lipids are crucial for fetal growth and development. Maternal lipid concentrations are associated with fetal growth in the second and third trimester of pregnancy and with birth outcomes. However, it is unknown if this association starts early in pregnancy or arises later during fetal development. The aim of this study was to investigate the association between the maternal lipid profile in early pregnancy and embryonic size., Methods: We included 1474 women from the Generation R Study, a population based prospective birth cohort. Both embryonic size and the maternal lipid profile were measured between 10 weeks + 1 day and 13 weeks + 6 days gestational age. The maternal lipid profile was defined as total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), remnant cholesterol, non-high-density (non-HDL-c) lipoprotein cholesterol concentrations and the triglycerides/high-density lipoprotein (TG/HDL-c) ratio. Additionally, maternal glucose concentrations were assessed. Embryonic size was assessed using crown-rump length (CRL) measurements. Associations were studied with linear regression models, adjusted for confounding factors: maternal age, pre-pregnancy body mass index (BMI), parity, educational level, ethnicity, smoking and folic acid supplement use., Results: Triglycerides and remnant cholesterol concentrations are positively associated with embryonic size (fully adjusted models, 0.17 SDS CRL: 95% CI 0.03; 0.30, and 0.17 SDS: 95% CI 0.04; 0.31 per 1 MoM increase, respectively). These associations were not present in women with normal weight (triglycerides and remnant cholesterol: fully adjusted model, 0.44 SDS: 95% CI 0.15; 0.72). Associations between maternal lipid concentrations and embryonic size were not attenuated after adjustment for glucose concentrations. Total cholesterol, HDL-c, LDL-c, non-HDL-c concentrations and the TG/HDL-c ratio were not associated with embryonic size., Conclusions: Higher triglycerides and remnant cholesterol concentrations in early pregnancy are associated with increased embryonic size, most notably in overweight women., Trial Registration: The study protocol has been approved by the Medical Ethics Committee of the Erasmus University Medical Centre (Erasmus MC), Rotterdam (MEC-2007-413). Written informed consent was obtained from all participants., (© 2022. The Author(s).)

Background: Coffee raises serum cholesterol because of its diterpenes, cafestol and kahweol, and the effect varies by brewing method. Population-based research on espresso coffee's impact on serum cholesterol is scarce. Our aim was to examine how various brewing methods, in particular espresso, were associated with serum total cholesterol (S-TC)., Methods: We used cross-sectional population data from the seventh survey of the Tromsø Study in Northern Norway (N=21 083, age ≥40 years). Multivariable linear regression was used to assess the association between S-TC as the dependent variable and each level of coffee consumption using 0 cups as the reference level, adjusting for relevant covariates and testing for sex differences., Results: Consumption of 3-5 cups of espresso daily was significantly associated with increased S-TC (0.09 mmol/L, 95% CI 0.01 to 0.17 for women and 0.16 mmol/L, 95% CI 0.07 to 0.24 for men), compared with participants drinking 0 cups of espresso per day. Consumption of ≥6 cups of boiled/plunger coffee daily was also associated with increased S-TC (0.30 mmol/L, 95% CI 0.13 to 0.48 for women and 0.23 mmol/L, 95% CI 0.08 to 0.38 for men), compared with participants drinking 0 cups of boiled/plunger coffee. Consumption of ≥6 cups of filtered coffee daily was associated with 0.11 mmol/L (95% CI 0.03 to 0.19) higher S-TC levels for women but not for men. Instant coffee consumption had a significant linear trend but showed no dose-response relationship when excluding participants not drinking instant coffee. There were significant sex differences for all coffee types except boiled/plunger coffee., Conclusion: Espresso coffee consumption was associated with increased S-TC with significantly stronger association for men compared with women. Boiled/plunger coffee was associated with increased S-TC in both sexes and with similar magnitude as shown in previous research. Filtered coffee was associated with a small increase in S-TC in women. Further research on espresso and S-TC is warranted., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The lipid content of mammalian cells varies greatly between cell type. Current methods for analysing lipid components of cells are technically challenging and destructive. Here, we report a facile, inexpensive method to identify lipid content - intracellular flow cytometric lipid analysis (IFCLA). Distinct lipid classes can be distinguished by Nile Blue fluorescence, Nile Red fluorescence or violet autofluorescence. Nile Blue is fluorescent in the presence of unsaturated fatty acids with a carbon chain length greater than 16. Cis-configured fatty acids induce greater Nile Blue fluorescence than their trans-configured counterparts. In contrast, Nile Red exhibits greatest fluorescence in the presence of cholesterol, cholesteryl esters, some triglycerides and phospholipids. Multiparametric spanning-tree progression analysis for density-normalized events (SPADE) analysis of hepatic cellular lipid distribution, including vitamin A autofluorescence, is presented. This flow cytometric system allows for the rapid, inexpensive and non-destructive identification of lipid content, and highlights the differences in lipid biology between cell types by imaging and flow cytometry., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2021. Published by The Company of Biologists Ltd.)

Sphingolipids and cholesterol are two lipid partners on cellular membranes where they form specific microdomains, named lipid rafts, which mediate specific cell functions. Sphingomyelin (SM) is one of the major sphingolipids. SM and free cholesterol are also two key lipids on the monolayer of plasma lipoproteins, including chylomicron, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), which participate in lipid transport in the circulation. Thus, sphingolipids and cholesterol play a fundamental role in cell membrane structure and blood lipid transport. In this chapter we will discuss the relationship between both lipids, on the cell membrane and in the circulation, as well as the impact of such relationship in the development of metabolic diseases., (© 2022. The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd.)

Context: The association between remnant cholesterol (remnant-C) and cardiovascular mortality in patients with type 2 diabetes (T2D) and incident diabetic nephropathy remains unclear., Objective: To examinie the association between remnant-C and cardiovascular mortality in patients with T2D, chronic kidney disease (CKD) stages 3 to 5, and newly diagnosed DN., Methods: This study determined the baseline lipid profile and searched for deaths with cardiovascular disease (CVD) within 2 years of baseline among 2282 adults enrolled between January 1, 2015 and December 31, 2016, who had T2D, CKD stages 3 to 5, and newly diagnosed DN. Adjusted logistic regression models were used to assess the associations between lipid, especially remnant-C concentration (either as continuous or categorical variables), and risk of cardiovascular mortality., Results: In multivariable-adjusted analyses, low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR], 1.022; 95% CI, 1.017-1.026, per 10 mg/dL), high-density lipoprotein cholesterol (HDL-C) (OR, 0.929; 95% CI, 0.922-0.936, per 5 mg/dL), non-HDL-C (OR, 1.024; 95% CI, 1.021-1.028, per 10 mg/dL), and remnant-C (OR, 1.115; 95% CI, 1.103-1.127, per 10 mg/dL), but not triglycerides were associated with cardiovascular mortality. Atherogenic dyslipidemia (triglycerides > 150 mg/dL [1.69 mmol/L] and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) was also associated with cardiovascular mortality (OR, 1.073; 95% CI, 1.031-1.116). Remnant-C greater than or equal to 30 mg/dL differentiated patients at a higher risk of cardiovascular mortality from those with lower concentrations, especially with interaction with LDL-C level greater than 100 mg/dL: The highest risk was found in patients with higher levels both of remnant-C and LDL-C (OR, 1.696; 95% CI, 1.613-1.783)., Conclusion: In patients with T2D, CKD stages 3 to 5, and incident DN, remnant-C was associated with a higher risk of death with CVD. Different from the general population, the interaction of remnant-C and LDL-C was associated with the highest risk of cardiovascular mortality., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To examine whether serum cholesterol in early middle age is associated with age-related macular degeneration (AMD) later in life., Methods: A group of Helsinki Businessmen Study (HBS) participants (n = 209) were recruited for the study. Total cholesterol (TC), triglyceride and body mass index (BMI) were measured at the HBS baseline visit in 1964-1973. Lipid subfractions, BMI, smoking status and statin use were recorded in 2011 and fundus photographs graded for AMD in 2005-2012. The subjects were genotyped for the main AMD risk single nucleotide polymorphisms (SNPs)., Results: TC measured at baseline 1964-1973 was significantly higher in subjects later developing intermediate or late AMD (6.67 mmol/l versus 6.20 mmol/l, p = 0.024) or with drusen size of ≥125 µm (6.68 mmol/l versus 6.21 mmol/l, p = 0.030) compared with the rest of the study population. TC, LDL and TG values at follow-up 2011 were lower in subjects with AMD compared to those without, whereas HDL levels showed no difference. In multivariate analysis, baseline TC associated with intermediate or late AMD (OR 1.59, p = 0.004) and drusen size ≥ 125 µm (OR 1.57, p = 0.006) when corrected for age, BMI, AMD risk SNPs and smoking. Lipid values measured 2011 had no associations after correction., Conclusions: High systemic total cholesterol in early middle age may have a role in the initial development of AMD, especially in patients later developing large drusen., (© 2021 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Background: Dietary saturated fat raises total cholesterol and LDL cholesterol levels. It is unclear whether these effects differ by the fatty acid chain lengths of saturated fats; particularly, it is unclear whether medium-chain fatty acids increase lipid levels., Objectives: We conducted a systematic review to determine the effects of medium-chain triglyceride (MCT) oil, consisting almost exclusively of medium-chain fatty acids (6:0-10:0), on blood lipids., Methods: We searched Medline and Embase through March 2020 for randomized trials with a minimum 2-week intervention period that compared MCT oil with another fat or oil. Outcomes were total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. Included studies were restricted to adults above 18 years of age. Studies conducted in populations receiving enteral or parenteral nutrition were excluded. Data were pooled using a random-effects meta-analysis., Results: Seven articles were included in the meta-analysis; LDL cholesterol and HDL cholesterol were reported in 6 studies. MCT oil intake did not affect total cholesterol (0.04 mmol/L; 95% CI, -0.11 to 0.20; I2 = 33.6%), LDL cholesterol (0.02 mmol/L; 95% CI, -0.13 to 0.17; I2 = 28.7%), or HDL cholesterol (-0.01 mmol/L; 95% CI, -0.10 to 0.09; I2 = 74.1%) levels, but did increase triglycerides (0.14 mmol/L; 95% CI, 0.01-0.27; I2 = 42.8%). Subgroup analyses showed that the effects of MCT oil on total cholesterol and LDL cholesterol differed based on the fatty acid profile of the control oil (Pinteraction = 0.003 and 0.008, respectively), with MCT oil increasing total cholesterol and LDL cholesterol when compared to a comparator consisting predominantly of unsaturated fatty acids, and with some evidence for reductions when compared to longer-chain SFAs., Conclusions: MCT oil does not affect total cholesterol, LDL cholesterol, or HDL cholesterol levels, but does cause a small increase in triglycerides., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background Anthropometric parameters of individuals are good at predicting functional impairment, mortality, and future cardiometabolic diseases. The relationship between anthropometric parameters and lipid profiles have been studied in different parts of the world. But to date, no such studies have been conducted in Nepal. Objective To investigate the association between anthropometric parameters and lipid profile in the adult population of Kaski district, Nepal. Method This study was carried out at Manipal Teaching Hospital, Pokhara, Kaski, Nepal. The fasting lipid profiles were analyzed in a total of 400 subjects aged > 18 years with an automated OCD Vitros 350 dry chemistry analyzer. The Kolmogorov-Smirnov test was used to test the normality of the data. The mean values of fasting lipids were compared within the subjects with different body mass index groups using ANOVA and waist circumference, waist-hip ratios, waist-height ratios, and neck circumference using independent samples t-test. The anthropometric indices evaluated were body mass index, waist circumference, waist-hip ratio, waist-height ratio, head circumference, neck circumference, and mid-upper arm circumference. Pearson's correlation coefficients and multiple regression analysis were performed to identify the association between the lipid profile and anthropometric parameters. The difference was considered statistically significant when p values (two-tailed) were < 0.050. Result The mean values of the serum lipid parameters other than high-density lipoprotein cholesterol were found to be higher in the subjects with an above than normal BMI, waist circumference, waist-hip ratio, waist-height ratio, and neck circumference. Pearson's correlation coefficient and multiple regression analysis showed that waistheight ratio best predicts serum triglycerides (β=0.622, p < 0.001) and high-density lipoprotein cholesterol (β=-0.711, p < 0.001) among all measured anthropometric parameters. Conclusion Among all the studied anthropometric parameters, the WHtR was found to be the most powerful predictor of serum triglycerides and high-density lipoprotein cholesterol.

Background: Adipocytes from lipodystrophic Agpat2 -/- mice have impaired adipogenesis and fewer caveolae. Herein, we examined whether these defects are associated with changes in lipid composition or abnormal levels of caveolae-associated proteins. Lipidome changes were quantified in differentiated Agpat2 -/- adipocytes to identify lipids with potential adipogenic roles., Methods: Agpat2 -/- and wild type brown preadipocytes were differentiated in vitro. Plasma membrane was purified by ultracentrifugation. Number of caveolae and caveolae-associated proteins, as well as sterol, sphingolipid, and phospholipid lipidome were determined across differentiation., Results: Differentiated Agpat2 -/- adipocytes had decreased caveolae number but conserved insulin signaling. Caveolin-1 and cavin-1 levels were equivalent between Agpat2 -/- and wild type adipocytes. No differences in PM cholesterol and sphingolipids abundance were detected between genotypes. Levels of phosphatidylserine at day 10 of differentiation were increased in Agpat2 -/- adipocytes. Wild type adipocytes had increased whole cell triglyceride, diacylglycerol, phosphatidylglycerol, phosphatidic acid, lysophosphatidylcholine, lysophosphatidylethanolamine, and trihexosyl ceramide, and decreased 24,25-dihydrolanosterol and sitosterol, as a result of adipogenic differentiation. By contrast, adipogenesis did not modify whole cell neutral lipids but increased lysophosphatidylcholine, sphingomyelin, and trihexosyl ceramide levels in Agpat2 -/- adipocytes. Unexpectedly, adipogenesis decreased PM levels of main phospholipids in both genotypes., Conclusion: In Agpat2 -/- adipocytes, decreased caveolae is not associated with changes in PM cholesterol nor sphingolipid levels; however, increased PM phosphatidylserine content may be implicated. Abnormal lipid composition is associated with the adipogenic abnormalities of Agpat2 -/- adipocytes but does not prevent insulin signaling., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is characterized by the presence of amyloid β (Aβ) plaques, tau tangles, inflammation, and loss of cognitive function. Genetic variation in a cholesterol transport protein, apolipoprotein E (apoE), is the most common genetic risk factor for sporadic AD. In vitro evidence suggests that apoE links to Aβ production through nanoscale lipid compartments (lipid clusters), but its regulation in vivo is unclear. Here, we use superresolution imaging in the mouse brain to show that apoE utilizes astrocyte-derived cholesterol to specifically traffic neuronal amyloid precursor protein (APP) in and out of lipid clusters, where it interacts with β- and γ-secretases to generate Aβ-peptide. We find that the targeted deletion of astrocyte cholesterol synthesis robustly reduces amyloid and tau burden in a mouse model of AD. Treatment with cholesterol-free apoE or knockdown of cholesterol synthesis in astrocytes decreases cholesterol levels in cultured neurons and causes APP to traffic out of lipid clusters, where it interacts with α-secretase and gives rise to soluble APP-α (sAPP-α), a neuronal protective product of APP. Changes in cellular cholesterol have no effect on α-, β-, and γ-secretase trafficking, suggesting that the ratio of Aβ to sAPP-α is regulated by the trafficking of the substrate, not the enzymes. We conclude that cholesterol is kept low in neurons, which inhibits Aβ accumulation and enables the astrocyte regulation of Aβ accumulation by cholesterol signaling., Competing Interests: Competing interest statement: D.M.H. is an inventor on a patent licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies. D.M.H. cofounded and is on the scientific advisory board of C2N Diagnostics. C2N Diagnostics has licensed certain anti-tau antibodies to AbbVie for therapeutic development. D.M.H. is on the scientific advisory board of Denali and consults for Genentech, Merck, Cajal Neuroscience, and Eli Lilly., (Copyright © 2021 the Author(s). Published by PNAS.)

Background: Hypercholesterolemia (plasma cholesterol concentration ≥5.2 mmol/L) is a risk factor for cardiovascular disease and stroke. Many different cholesterol self-tests are readily available at general stores, pharmacies and web shops. However, there is limited information on their analytical and diagnostic performance., Methods: We included 62 adult patients who required a lipid panel measurement (cholesterol, high-density lipoprotein (HDL), triglycerides and LDL calc ) for routine care. The performance of five different cholesterol self-tests, three quantitative meters ( Roche Accutrend Plus , Mission 3-in-1 and Qucare ) and two semi-quantitative strip tests ( Veroval and Mylan MyTest ), was assessed according to the manufacturers' protocol., Results: The average plasma cholesterol concentration was 5.2 ± 1.2 mmol/L. The mean absolute relative difference (MARD) of the five cholesterol self-tests ranged from 6 ± 5% ( Accutrend Plus ) to 20 ± 12% ( Mylan Mytest ). The Accutrend Plus cholesterol meter showed the best diagnostic performance with a 92% sensitivity and 89% specificity. The Qucare and Mission 3-in-1 are able to measure HDL concentrations and can thus provide a cholesterol:HDL ratio. The Passing-Bablok regression analyses for the ratio showed poor performance in both self-tests ( Mission 3-in-1 : y = 1.62x-1.20; Qucare : y = 0.61x + 1.75). The Accutrend Plus is unable to measure the plasma high-density lipoprotein concentration.Conclusions/interpretation: The Accutrend Plus cholesterol meter (Roche) had excellent diagnostic and analytic performance. However, several of the commercially-available self-tests had considerably poor accuracy and diagnostic performance and therefore do not meet the required qualifications, potentially leading to erroneous results. Better regulation, standardization and harmonization of cholesterol self-tests is warranted.

Background: The lipid profile is reportedly related to peripheral blood pressure or pulse wave velocity. However, no studies have investigated the associations between lipid parameters, especially remnant lipoprotein cholesterol (RLP-C), and central systolic blood pressure (cSBP)., Methods: This study used baseline data of a community-based cohort in Beijing, China. Participants who had been treated with anti-hypertensive or lipid-lowering agents were excluded. RLP-C is equal to total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). An Omron HEM-9000AI device was used to measure non-invasive cSBP. The associations between blood lipid profile and non-invasive cSBP were evaluated using multivariable regression models., Results: The 5173 included participants were 55.0 ± 8.5 years old; 35.7% (1845) of participants were men. Increased cSBP was significantly associated with increased TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), and RLP-C but with decreased HDL-C, even after adjusting for possible covariates. When simultaneously entering individual pairs of RLP-C and other blood lipid parameters into the multivariable regression model, RLP-C remained significantly associated with cSBP, even after adjusting for other lipids. Compared with participants who had RLP-C levels in the first quartile (Q1), cSBP for those with RLP-C in Q4 was increased to 4.57 (95% confidence interval [CI]: 3.08-6.06) mmHg after adjusting for LDL-C, 4.50 (95%CI: 2.98-6.02) mmHg after adjusting for TC, 3.91 (95%CI: 1.92-5.89) mmHg after adjusting for TG, 5.15 (95%CI: 3.67-6.63) mmHg after adjusting for HDL-C, and 4.10 (95%CI: 2.36-5.84) mmHg after adjusting for non-HDL-C., Conclusions: Increased blood RLP-C level was significantly associated with higher cSBP in a Chinese population, independently of other lipids, which indicates its importance in individual cardiovascular risk assessment.

Nutrition determines our health, both directly and indirectly. Consumed foods affect the functioning of individual organs as well as entire systems, e.g., the cardiovascular system. There are many different diets, but universal guidelines for proper nutrition are provided in the WHO healthy eating pyramid. According to the latest version, plant products should form the basis of our diet. Many groups of plant compounds with a beneficial effect on human health have been described. Such groups include anthocyanins and iridoids, for which it has been proven that their consumption may lead to, inter alia, antioxidant, cholesterol and lipid-lowering, anti-obesity and anti-diabetic effects. Transcription factors directly affect a number of parameters of cell functions and cellular metabolism. In the context of lipid and cholesterol metabolism, five particularly important transcription factors can be distinguished: liver X receptor (LXR), peroxisome proliferator-activated receptor-α (PPAR-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer binding protein α (C/EBPα) and sterol regulatory element-binding protein 1c (SREBP-1c). Both anthocyanins and iridoids may alter the expression of these transcription factors. The aim of this review is to collect and systematize knowledge about the impact of anthocyanins and iridoids on transcription factors crucial for lipid and cholesterol homeostasis.

A rich diversity of transmembrane G protein-coupled receptors (GPCRs) are used by eukaryotes to sense physical and chemical signals. In humans alone, 800 GPCRs comprise the largest and most therapeutically targeted receptor class. Recent advances in GPCR structural biology have produced hundreds of GPCR structures solved by X-ray diffraction and increasingly, cryo-electron microscopy (cryo-EM). Many of these structures are stabilized by site-specific cholesterol binding, but it is unclear whether these interactions are a product of recurring cholesterol-binding motifs and if observed patterns of cholesterol binding differ by experimental technique. Here, we comprehensively analyze the location and composition of cholesterol binding sites in the current set of 473 human GPCR structural chains. Our findings establish that cholesterol binds similarly in cryo-EM and X-ray structures and show that 92% of cholesterol molecules on GPCR surfaces reside in predictable locations that lack discernable cholesterol-binding motifs., Competing Interests: Declaration of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The aim of present study was to investigate the association of acrylamide (AA) hemoglobin biomarkers and serum lipids level in a general population. Data set of our study were extracted from an open database - National Health and Nutrition Examination Surveys (NHANES) 2013-2016. In total 2899 participants were enrolled. The associations between AA hemoglobin parameters [hemoglobin adducts of AA (HbAA) and glycidamide (HbGA), total of HbAA and HbGA (HbAA+HbGA), and ratio of HbGA to HbAA (HbGA/HbAA)] and lipid levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C)] were analyzed. Generalized linear models and restricted cubic spline plots were conducted to address the relationship between lipid levels and acrylamide markers. Comparing the lowest quantiles, HbGA and HbGA/HbAA both remained a significant trend regardless of lipid types. Analyses using a generalized linear model with restricted cubic spline and validated with regression models, all 4 AA parameters demonstrated a linear association and positive correlation with TG. Furthermore, there were also opposite nonlinear association between HbGA/HbAA and LDL-C (positive correlation), and HbGA/HbAA and HDL-C (negative correlation). Further analysis with threshold effect analysis or regression analysis showed HbGA and HbGA/HbAA remained significant association with all TC, TG, LDL-C, and HDL-C. The hemoglobin adducts AA parameters as long-term exposure biomarkers are associated with the atherosclerotic lipid changes in a population of US adults., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Hypocholesterolemia is a marker of liver disease, and patients with a Fontan circulation may have hypocholesterolemia secondary to Fontan-associated liver disease or inflammation. We investigated circulating lipids in adults with a Fontan circulation and assessed the associations with clinical characteristics and adverse events. Methods and Results We enrolled 164 outpatients with a Fontan circulation, aged ≥18 years, in the Boston Adult Congenital Heart Disease Biobank and compared them with 81 healthy controls. The outcome was a combined outcome of nonelective cardiovascular hospitalization or death. Participants with a Fontan (median age, 30.3 [interquartile range, 22.8-34.3 years], 42% women) had lower total cholesterol (149.0±30.1 mg/dL versus 190.8±41.4 mg/dL, P <0.0001), low-density lipoprotein cholesterol (82.5±25.4 mg/dL versus 102.0±34.7 mg/dL, P <0.0001), and high-density lipoprotein cholesterol (42.8±12.2 mg/dL versus 64.1±16.9 mg/dL, P <0.0001) than controls. In those with a Fontan, high-density lipoprotein cholesterol was inversely correlated with body mass index ( r =-0.30, P <0.0001), high-sensitivity C-reactive protein ( r =-0.27, P =0.0006), and alanine aminotransferase ( r =-0.18, P =0.02) but not with other liver disease markers. Lower high-density lipoprotein cholesterol was independently associated with greater hazard for the combined outcome adjusting for age, sex, body mass index, and functional class (hazard ratio [HR] per decrease of 10 mg/dL, 1.37; 95% CI, 1.04-1.81 [ P =0.03]). This relationship was attenuated when log high-sensitivity C-reactive protein was added to the model (HR, 1.26; 95% CI, 0.95-1.67 [ P =0.10]). Total cholesterol, low-density lipoprotein cholesterol, and triglycerides were not associated with the combined outcome. Conclusions The Fontan circulation is associated with decreased cholesterol levels, and lower high-density lipoprotein cholesterol is associated with adverse outcomes. This association may be driven by inflammation. Further studies are needed to understand the relationship between the severity of Fontan-associated liver disease and lipid metabolism.

Background: Increased levels of plasma lipoproteins are among some of the modifiable risk factors for cardiovascular disease (CVD). Dietary changes and increased physical activity are the most powerful non-pharmacological interventions for achieving optimal plasma lipid levels., Objectives: To investigate the effect of an intensive short-term lifestyle intervention on plasma lipid trajectories in overweight non-diabetic females., Material and Methods: A total of 202 healthy overweight (body mass index (BMI) >27.5 kg/m2) females underwent an intensive short-term (ten-week) intervention (at least 4 units of one-hour exercise activity weekly at optimal energy intake) aimed at lowering body weight. Plasma lipid (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)) levels were examined at baseline and every 2 weeks over the course of the ten-week intervention., Results: There was a significant decrease in BMI (Δ -4.7%, p < 0.001) and body weight (Δ -4.9%, p < 0.001) after the intervention. Positive changes (decreases) in TC (Δ -8%, p < 0.001), TG (Δ -9%, p < 0.001) and LDL-C (Δ -11%, p < 0.001) were observed immediately after 2 weeks, but levels did not decrease further thereafter. In contrast, HDL-C did not increase as expected: after 2 weeks of intervention, we observed a significant decrease of about 6% (p < 0.001) followed by a slow return to baseline values. But even after 10 weeks of intervention, HDL-C values had not reached the values detected at baseline., Conclusions: In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.

Background & Objective(s): Bertholletia excelsa is a rich herbal source of anti-oxidants and phenols. The goal of this study is to evaluation the effect of bertholletia excelsa nut on body weight, C-reactive protein (CRP) and lipid profile., Methods: A literature search was conducted in PubMed, Scopus and Web of sciences databases by two reviewers up to October 2019. Random effect model used to combine results., Results: Six studies included in analysis with 71 participants. The population was public population. Pooled results showed Bertholletia excelsa have reduction effect on triglyceride weighted mean difference (WMD: -8.23 mg/dl, 95 % CI -15.09, -1.38, I² = 0%), Cholesterol (WMD: -14.31 mg/dl, 95 % CI -23.38, -5.24, I² = 47 %), Low-density lipoprotein (LDL) (WMD: -9.27 mg/dl, 95 % CI -13.48, -5.06, I² = 0%)., Conclusion: This study provided an evidence that Bertholletia excelsa nuts have reduction effect on triglyceride, cholesterol, and LDL levels., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: It is well established that patients with systemic sclerosis (SSc) have a disrupted lipid profile and an increased cardiovascular risk. Cholesterol efflux capacity (CEC), the ability of high-density lipoprotein (HDL)-cholesterol to accept cholesterol from macrophages, has been linked to cardiovascular events. The aim of this study was to establish whether CEC and lipid profile were impaired in SSc patients with respect to controls and whether these changes were associated with disease-related data., Methods: Cross-sectional study encompassed 188 individuals: 73 SSc patients and 115 controls. CEC, using an in vitro assay, and lipoprotein serum concentrations were assessed in patients and controls. A multivariable analysis was performed to study the differences in CEC between patients and controls, and if SSc-related data could explain such differences., Results: The multivariable analysis adjusted for demographic characteristics, cardiovascular risk factors, and lipid-related molecules showed that total cholesterol (beta coefficient: - 22 [95%CI - 37 to - 7], p = 0.004), triglycerides (beta coefficient: 24 [95%CI 2-47], p = 0.033), lipoprotein A (beta coefficient: 22 [95%CI 2-43], p = 0.033), and CEC (beta coefficient: - 6 [95%CI - 10 to - 2]%,p = 0.002) were significantly different between patients and controls. Skin thickness, as assessed by modified Rodnan skin score, was independently associated with a lower CEC (beta coefficient: - 0.21 [95%CI - 0.37 to - 0.05]%, p = 0.011) after multivariable adjustment., Conclusion: SSc patients show an abnormal lipid profile with respect to controls including CEC. Skin thickness is independent and inversely associated with CEC in SSc patients.

The number of nutrigenetic studies dedicated to the identification of single nucleotide polymorphisms (SNPs) modulating blood lipid profiles in response to dietary interventions has increased considerably over the last decade. However, the robustness of the evidence-based science supporting the area remains to be evaluated. The objective of this review was to present recent findings concerning the effects of interactions between SNPs in genes involved in cholesterol metabolism and transport, and dietary intakes or interventions on circulating cholesterol concentrations, which are causally involved in cardiovascular diseases and established biomarkers of cardiovascular health. We identified recent studies (2014-2020) that reported significant SNP-diet interactions in 14 cholesterol-related genes ( NPC1L1, ABCA1, ABCG5, ABCG8, APOA1, APOA2, APOA5, APOB, APOE, CETP, CYP7A1, DHCR7, LPL, and LIPC ), and which replicated associations observed in previous studies. Some studies have also shown that combinations of SNPs could explain a higher proportion of variability in response to dietary interventions. Although some findings still need replication, including in larger and more diverse study populations, there is good evidence that some SNPs are consistently associated with differing circulating cholesterol concentrations in response to dietary interventions. These results could help clinicians provide patients with more personalized dietary recommendations, in order to lower their risk for cardiovascular disease.

Dietary fatty acids (FA) are essential for overall human health, yet individual FA reference ranges have yet to be established. Developing individual FA reference ranges can provide context to reported concentrations and whether an individual displays deficient, or excess amounts of FA. Reference ranges of sixty-seven individual FA (μmol/L) were profiled and analyzed using gas chromatography with a flame ionization detector from serum samples collected from 476 middle-aged Singaporean males (BMI:23.3 ± 2.9) and females (BMI:21.8 ± 3.6). Measures of triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) (mmol/L) were also collected. The mean FA concentration seen in this cohort (11,458 ± 2478 was similar to that of overweight North American cohorts assessed in past studies. Ten biologically relevant FA were compared between sexes, with females exhibiting significantly higher concentrations in four FA ( p < 0.05). A multiple regression model revealed the ten FA contributed significantly to nearly all lipid biomarkers ( p < 0.05). A majority of participants who had FA concentrations in the ≥95th percentile also exhibited TG, HDL, LDL, and TC levels in the "high" risk classification of developing cardiovascular disease. Future studies profiling individual FA reference ranges in many unique, global cohorts are necessary to develop cut-off values of individual FA concentrations highly related to disease-risk.

Supported by an abundance of experimental and genetic evidence, angiopoietin-like protein 3 (ANGPTL3) has emerged as a promising therapeutic target for cardiovascular disease. ANGPTL3 is primarily produced by the liver and is a potent modulator of plasma lipids and lipoproteins. Experimental models and subjects with loss-of-function Angptl3 mutations typically present with lower levels of HDL-C than noncarriers. The effect of ANGPTL3 on HDL-C is typically attributed to its function as an inhibitor of the enzyme endothelial lipase. The ability to facilitate reverse cholesterol transport (RCT), the transport of cholesterol from peripheral tissues back to the liver, is a proposed antiatherogenic property of HDL. However, the effect of ANGPTL3 inhibition on RCT remains unclear. Here, we performed a series of dose-response and RCT studies using an Angptl3 antisense oligonucleotide (ASO) in mouse models with varying plasma lipid profiles ranging from moderately to severely hyperlipidemic. Angptl3 ASO-mediated reduction in HDL-C was limited to the model with moderate lipidemia, where the majority of plasma cholesterol was associated with HDL. Surprisingly, regardless of the effect on HDL-C, treatment with the Angptl3 ASO enhanced RCT in all models tested. The observations from the RCT assays were confirmed in HDL clearance studies, where mice treated with the Angptl3 ASO displayed increased plasma clearance and hepatic uptake of labeled HDL. The results from our studies suggest that inhibition of ANGPTL3 not only reduces levels of proatherogenic lipids but also improves HDL-mediated RCT., Competing Interests: Conflict of interest All authors are employees of Ionis Pharmaceuticals., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)