Changes In Lipid Levels Research Articles

Lipids and Amyotrophic Lateral Sclerosis: A two-sample Mendelian Randomization Study.

Previous observational studies revealed a potential but partially controversial relation between lipid metabolism and risk of amyotrophic lateral sclerosis (ALS), potentially prone to bias. Therefore, we aimed to study whether lipid metabolism involves genetically determined risk factors for ALS through Mendelian randomization (MR) analysis. Using GWASs summary-level data for total cholesterol (TC) (n=188,578), high-density lipoprotein cholesterol (HDL-C) (n=403,943), low-density lipoprotein cholesterol (LDL-C) (n=440,546), apolipoprotein A1(ApoA1) (n=391,193), apolipoprotein B (ApoB) (n=439,214), and ALS (12,577 cases and 23,475 controls), we implemented a bidirectional MR study to evaluate a genetic relation between lipids and ALS risk. We performed a mediation analysis to assess whether LDL-C is a potential mediator on the pathway from traits of LDL-C-related polyunsaturated fatty acids (PUFAs) to ALS risk. We identified genetically predicted increased lipid levels to be associated with the risk of ALS, whereby elevated LDL-C had the most potent effect (OR, 1.028; 95% CI, 1.008-1.049, p=0.006). The effect of increased levels of apolipoproteins on ALS was similar to their corresponding lipoproteins. ALS did not cause any changes in lipid levels. We found no relation between LDL-C-modifying lifestyles and ALS. The mediation analysis revealed that LDL-C could act as an active mediator for linoleic acid, with the mediation effect estimated to be 0.009. We provided high-level genetic evidence verifying the positive link between preclinically elevated lipid and ALS risk that had been described in previous genetic and observational studies. We also demonstrated the mediating role of LDL-C in the pathway from PUFAs to ALS.

Relationship between Changes in Blood Glucose and Blood Lipid Levels and the Risk of Thyroid Cancer in Patients with Type 2 Diabetes Mellitus.

To investigate the relationship between changes in blood glucose and blood lipid levels and the risk of thyroid cancer in patients with type 2 diabetes mellitus. A total of 159 patients with type 2 diabetes who were treated in our hospital between June 2018 and February 2021 were recruited and assigned into the observation group, including 136 patients with type 2 diabetes without thyroid cancer (nonthyroid cancer group) and 23 patients with type 2 diabetes complicated with thyroid cancer (thyroid cancer group), and 120 healthy subjects during the same period were selected as the control group. Glycated hemoglobin (HbAlc), total cholesterol (TC), triacylglycerol (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were detected and compared. Pearson's method was conducted to analyze the correlation between serum HbAlc level and TC, TG, HDL-C, and LDL-C levels in patients with type 2 diabetes mellitus; multivariate logistic regression analysis was performed to analyze the influencing factors of thyroid cancer in patients with type 2 diabetes mellitus. The serum HbAlc level and the incidence of thyroid cancer in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group (P < 0.05). The levels of TC, TG, and LDL-C in patients with type 2 diabetes mellitus in the observation group were significantly higher than those in the control group, and the level of HDL-C was significantly lower than that in the control group (P < 0.05). The correlation analysis showed that serum HbAlc levels in patients with type 2 diabetes were positively correlated with TC and TG levels and negatively correlated with HDL-C levels (P < 0.05) and not correlated with LDL-C levels (P > 0.05). Compared with the type 2 diabetes patients without thyroid cancer, the serum HbAlc, TC, and TG levels of the patients with type 2 diabetes mellitus in the thyroid cancer group were significantly higher, and the levels of HDL-C were significantly lower (P < 0.05). There was no significant change in the level of LDL-C (P > 0.05). Multivariate logistic regression analysis showed that serum HbAlc, TC, and TC levels were all risk factors for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05), while serum HDL-C level was a protective factor for thyroid cancer in patients with type 2 diabetes mellitus (P < 0.05). Thyroid cancer in type 2 diabetes patients may be linked to elevated levels of blood HbAlc, TC, and TG. HbAlc may raise the risk of thyroid cancer in type 2 diabetes patients by modulating blood lipid levels, which might serve as a marker to assess the risk of thyroid cancer in type 2 diabetes mellitus patients. However, since this study did not conduct in vitro and in vivo experiments, how HbAlc affects the pathogenesis of thyroid cancer has not been described in this study, which is also our future research direction. It is expected to provide new ideas for the prevention and treatment of thyroid cancer.

Fecal microbiota transplantation from Suncus murinus, an obesity-resistant animal, to C57BL/6NCrSIc mice, and the antibiotic effects in the approach.

Important studies on the relationship of the intestinal microbial flora with obesity have uncovered profound changes in the composition of the gut microbiota in obese individuals. Animal studies successfully altered body phenotypes by fecal microbiota transplantation (FMT). In this study, we analyzed the gut microbiome of Suncus murinus (S. murinus), a naturally obesity-resistant animal, and the changes of the gut flora of C57BL/6NCrSIc mice that received gut bacteria transplantation from S. murinus by 16S rRNA gene analysis method. And analyzed and discussed the possible impact of the use of antibiotics before transplantation on the outcome of transplantation. Our results showed no significant changes in body weight in the FMT group compared to the control (AB) group, but large fluctuations due to antibiotics. There was no change in blood lipid levels between groups before and after FMT. The gut microbiota of S. murinus were enriched in Firmicutes and Proteobacteria, while Bacteroidetes were not detected, and fewer OTUs were detected in the intestine gut in comparison to other mouse groups. Statistically significant differences in alpha diversity were observed between the FMT group and other groups. Furthermore, a beta diversity analysis indicated an apparent structural separation between the FMT group and other groups. It was suggested that the gut flora of S. murinus was not well established in the gut trace of mice through FMT, and the administration of antibiotics before transplantation was an important factor affecting the overall composition of the gut flora. Although FMT of S. murinus failed to completely colonize the intestinal tract of the mice, it still had a certain effect on the establishment of the intestinal flora of the mice. The unpredictable effects of pre-transplantation antibiotics on the results of transplantation cannot be ignored.

Abstract 414: Targeting lipid metabolism to improve efficacy of braf-targeted therapy in colorectal cancer

Abstract Background: Aberrant lipid metabolism is associated with poor prognosis in colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of lipogenesis, is overexpressed and a therapeutic target in CRC. Overexpression of CD36, a fatty acid translocase, plays a pro-tumorigenic role in CRC. BRAFV600E is the mutation occurring in about 10-15% of CRC cases. BRAF-targeted therapy is effective, but quickly developed resistance is an issue. Our preliminary data show that development of resistance to BRAF-targeted therapy is associated with an increase in expression of FASN, CD36, accumulation of triglycerides (TGs), and mitochondrial respiration. Therefore, our central hypothesis is that inhibition of lipid metabolism will sensitize CRC cells to BRAF inhibitors and overcome acquired resistance. Methods: We established HT29 cells and primary PT130 and PT2449pt cells resistant to PLX8394, a novel BRAF inhibitor. IC50 curves, PrestoBlue viability, CytoSelect™ 24-Well Cell Invasion, and Triglyceride Assays, Seahorse XF analysis, western blot, and confocal microscopy were used to evaluate differences between parental and resistant cells. RNA-seq and lipid analysis were used to evaluate changes in gene expression and lipids levels. Combination of PLX8394 and TVB3664 (FASN inhibitor) was tested on cell viability in parental and resistant cells. Results: PLX8394 resistant cells have a higher IC50, an increased proliferation, and invasion compared to parental cells. An increase in invasion of resistant cells is associated with a decrease in E-cadherin. RNA sequencing shows a significant increase in FASN expression. Western blot on resistant cells confirms upregulation of FASN, CD36, and other lipogenic markers. Consistently, resistant cells have an increase in levels of triglycerides as compared to parental cells. Seahorse XF Cell Mito Stress Test shows that resistant cells forgo the Warburg effect and instead rely more heavily on oxidative phosphorylation. To further support our hypothesis, FASN shRNA knockdown of FASN in parental HT29 cells is more susceptible to PLX8394 treatment compared to control. We also observed the synergetic effect of PLX8394 and TVB3664 treatment on cell viability in parental cells, but not in resistant cells. Conclusion: Our study demonstrates that resistance to BRAF inhibitors is associated with a significant increase in proliferation, metastasis, and upregulation of lipid metabolism. We show that combination of FASN and BRAF inhibitors has a combinational effect on inhibiting cell viability in parental but not resistant cells, suggesting that the addition of FASN inhibitor to the standard regimen for BRAFV600E mutation positive patients can improve efficacy of these therapies. Additional screening of lipid metabolism-targeted therapies in combination with standard BRAF regimens are needed to develop novel and more efficacious strategies for CRC patients with BRAF mutations. Citation Format: Mariah E. Geisen, Dang he, Chi Wang, Jill M. Kolesar, Yekaterina Zaytseva. Targeting lipid metabolism to improve efficacy of braf-targeted therapy in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 414.

Interleukin 6 Blockade With Tocilizumab Diminishes Indices of Inflammation That Are Linked to Mortality in Treated Human Immunodeficiency Virus Infection.

People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine. This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses of TCZ or matching placebo intravenously. Following a 10-week treatment period and a 12-week washout, participants were switched to the opposite treatment. The primary endpoints were safety and posttreatment levels of C-reactive protein (CRP) and CD4+ T-cell cycling. Secondary endpoints included changes in inflammatory indices and lipid levels. There were 9 treatment-related toxicities of grade 2 or greater during TCZ administration (mostly neutropenia) and 2 during placebo administration. Thirty-one of 34 participants completed the study and were included in a modified intent-to-treat analysis. TCZ reduced levels of CRP (median decrease, 1819.9 ng/mL, P < .0001; effect size, 0.87) and reduced inflammatory markers in PWH, including D-dimer, soluble CD14, and tumor necrosis factor receptors. T-cell cycling tended to decrease in all maturation subsets after TCZ administration, but was only significant among naive CD4 T cells. Lipid levels, including lipid classes that have been related to cardiovascular disease risk, increased during TCZ treatment. TCZ is safe and decreases inflammation in PWH; IL-6 is a key driver of the inflammatory environment that predicts morbidity and mortality in ART-treated PWH. The clinical significance of lipid elevations during TCZ treatment requires further study. Clinical Trials Registration. NCT02049437.

High fat diet and PCSK9 knockout modulates lipid profile of the liver and changes the expression of lipid homeostasis related genes

BackgroundHigh fat diet (HFD) increases the likelihood of dyslipidemia, which can be a serious risk factor for atherosclerosis, diabetes or hepatosteatosis. Although changes in different blood lipid levels were broadly investigated, such alterations in the liver tissue have not been studied before. The aim of the current study was to investigate the effect of HFD on hepatic triglyceride (TG), diglyceride (DG) and ceramide (CER) levels and on the expression of four key genes involved in lipid homeostasis (Pcsk9, Ldlr, Cd36 and Anxa2) in the liver. In addition, the potential role of PCSK9 in the observed changes was further investigated by using PCSK9 deficient mice.MethodsWe used two in vivo models: mice kept on HFD for 20 weeks and PCSK9−/− mice. The amount of the major TGs, DGs and CERs was measured by using HPLC–MS/MS analysis. The expression profiles of four lipid related genes, namely Pcsk9, Ldlr, Cd36 and Anxa2 were assessed. Co-localization studies were performed by confocal microscopy.ResultsIn HFD mice, hepatic PCSK9 expression was decreased and ANXA2 expression was increased both on mRNA and protein levels, and the amount of LDLR and CD36 receptor proteins was increased. While LDLR protein level was also elevated in the livers of PCSK9−/− mice, there was no significant change in the expression of ANXA2 and CD36 in these animals. HFD induced a significant elevation in the hepatic levels of all measured TG and DG but not of CER types, and increased the proportion of monounsaturated vs. saturated TGs and DGs. Similar changes were detected in the hepatic lipid profiles of HFD and PCSK9−/− mice. Co-localization of PCSK9 with LDLR, CD36 and ANXA2 was verified in HepG2 cells.ConclusionsOur results show that obesogenic HFD downregulates PCSK9 expression in the liver and causes alterations in the hepatic lipid accumulation, which resemble those observed in PCSK9 deficiency. These findings suggest that PCSK9-mediated modulation of LDLR and CD36 expression might contribute to the HFD-induced changes in lipid homeostasis.

Frequencies of variants in genes associated with dyslipidemias identified in Costa Rican genomes.

Dyslipidemias are risk factors in diseases of significant importance to public health, such as atherosclerosis, a condition that contributes to the development of cardiovascular disease. Unhealthy lifestyles, the pre-existence of diseases, and the accumulation of genetic variants in some loci contribute to the development of dyslipidemia. The genetic causality behind these diseases has been studied primarily on populations with extensive European ancestry. Only some studies have explored this topic in Costa Rica, and none have focused on identifying variants that can alter blood lipid levels and quantifying their frequency. To fill this gap, this study focused on identifying variants in 69 genes involved in lipid metabolism using genomes from two studies in Costa Rica. We contrasted the allelic frequencies with those of groups reported in the 1000 Genomes Project and gnomAD and identified potential variants that could influence the development of dyslipidemias. In total, we detected 2,600 variants in the evaluated regions. However, after various filtering steps, we obtained 18 variants that have the potential to alter the function of 16 genes, nine variants have pharmacogenomic or protective implications, eight have high risk in Variant Effect Predictor, and eight were found in other Latin American genetic studies of lipid alterations and the development of dyslipidemia. Some of these variants have been linked to changes in blood lipid levels in other global studies and databases. In future studies, we propose to confirm at least 40 variants of interest from 23 genes in a larger cohort from Costa Rica and Latin American populations to determine their relevance regarding the genetic burden for dyslipidemia. Additionally, more complex studies should arise that include diverse clinical, environmental, and genetic data from patients and controls and functional validation of the variants.

Evinacumab in severe hypertriglyceridemia with or without lipoprotein lipase pathway mutations: a phase 2 randomized trial

Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial (NCT03452228) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations (n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations (n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations (n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg−1 or placebo every 4 weeks over a 12-week double-blind treatment period, followed by a 12-week single-blind treatment period. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3. Evinacumab reduced triglycerides in cohort 3 by a mean (s.e.m.) of −27.1% (37.4) (95% confidence interval −71.2 to 84.6), but the prespecified primary end point was not met. No notable differences in adverse events between evinacumab and placebo treatment groups were seen during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG. Trial registration number: ClinicalTrials.gov NCT03452228.

The relationship between serum lipid and sudden sensorineural hearing loss

Background Hyperlipidemia may be part of the important mechanisms for the development of idiopathic sudden sensorineural hearing loss (ISSNHL). Aims So the purpose of this study was to evaluate the relationship between changes in blood lipid levels and ISSNHL. Materials and Methods We enrolled 90 ISSNHL patients in our hospital using a retrospective study design from 2019.1 to 2021.12. Blood levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL-C). Hearing recovery was analyzed using the chi-square test and one-way analysis of variance (ANONA). Univariate and multifactorial Logstic retrospective analyses to establish the relationship between LDL-C/HDL-C ratio and hearing recovery after adjustment for potential confounding factors. Results In our study, 70 (77.78%) patients had their hearing recovered. All group analyses and three group analyses (i.e. Excluding the no-recovery group) found that LDL/HDL was on an upward trend from complete recovery to a slight recovery group and strongly associated with hearing recovery. Univariate and multivariate logistic regression analysis found high levels of LDL and LDL/HDL in the partial hearing recovery group, relative to the full hearing recovery group. Curve fitting intuitively demonstrates the influence of blood lipids on prognosis. Conclusions Our findings suggest that LDL. TC, TC/HDL, and LDL/HDL concentrations may be closely related to the pathogenesis of ISSNHL. Significance Improving the relevant lipid test at the time of admission to the hospital has good clinical significance for improving the prognosis of ISSNHL.

Association of serum lipid levels and clinical outcomes in early breast cancer patients.

The association between dyslipidaemia and breast cancer remains controversial, especially regarding the dynamic changes in lipid levels. This study aimed to elucidate the role of serum lipid levels and the changes in disease outcomes in patients with breast cancer. The lipid profiles of patients with breast cancer who underwent surgery between 2013 and 2017 were retrospectively reviewed. The lipid profiles comprised triglyceride (TG), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein. Serum lipid levels were categorized into three groups based on the tertiles. The Wilcoxon test was used to compare changes in serum lipid levels during follow-up. Hazard ratios (HRs) for survival outcomes were estimated using a multivariate Cox regression analysis. A total of 3499 women diagnosed with nonmetastatic invasive breast cancer were included in this study, with a median follow-up of 60.4 months. We confirmed that each 1-tertile increased TG at baseline [HR = 1.19, 95% confidence interval (CI) 1.02-1.39] and 1-year follow-up (HR = 1.46, 95% CI 1.07-1.98) led to worse relapse-free survival (RFS). A lower risk of disease relapse was observed with each 1-tertile upregulation in HDL at 1-year follow-up (HR = 0.72, 95% CI 0.56-0.92). Receiving systemic therapies tends to induce an elevation in plasma lipid levels 1 year after surgery, especially in terms of TG. Regarding the prognostic value of dynamic changes in lipid levels, patients with sustained high levels of TG had poorer RFS (HR = 1.90, 95% CI 1.16-3.11), whereas maintaining high levels of HDL led to better survival (HR = 0.60, 95% CI 0.37-0.97). High TG at baseline and during follow-up was associated with worse disease outcome in early breast cancer patients. Systemic treatment would lead to an elevation of serum lipid levels. Patients with sustained high HDL level at 1-year follow-up after surgery had a superior prognosis, warranting further clinical evaluation.

Changes in lipid levels in patients with obstructive sleep apnea

Changes in lipid levels in patients with obstructive sleep apnea

Lipidni status transrodnih osoba koje su na terapiji gonadnim hormonima suprotnog pola šest meseci

Introduction: The term "transgender" refers to a person whose sex assigned at birth does not match their gender identity. Transsexualism can be diagnosed in all ages, although the first signs can be seen in early childhood. This condition is treated with cross-sex hormone therapy (CSHT) and surgical reconstructions with the goal of matching the physical sex with the one that the person identifies with. Aim: To study the effects of cross-sex hormone therapy with testosterone on anthropometric characteristics, lipid and hormone status in trans men (female to male (FtM) transgenders). Material and methods: The study includes 31 FtM patients with a gender identity disorder. The beginning of CSHT was at age 26.03 ± 5.21. Patients were treated at the Clinic of Endocrinology, diabetes and metabolic diseases, University Clinical Center of Serbia. Lipid and hormone status before and during therapy were analyzed. Results: The BMI has increased significantly. Mean levels of HDL and Lp(a) were decreased significantly, and there was a significant decrease in ApoA1. There were no changes in other lipid levels. During six months of testosterone therapy levels of FSH, LH and estradiol showed a significant decrease, while testosterone has increased significantly. Higher values of RBC and hemoglobin were found. Conclusion: CSHT with testosterone do not lead to pathological alteration of lipid profile if dosed properly.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis

BackgroundNonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. MethodsThe effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. ResultsSAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of β-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. ConclusionSAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

Dendrobium Multi-Omics Reveal Lipid Remodeling in Response to Freezing.

Freezing damage is a common phenomenon responsible for reduced yields of economic crops. Regulation of lipid metabolism plays an important role in plant growth and adaptation during freezing. We previously carried out transcriptome and untargeted metabolome analyses to determine the regulation of flavonol and anthocyanin biosynthesis during freezing treatment (FT) and post-freezing recovery (FR) in Dendrobium catenatum. However, changes in lipid levels are hard to confirm by untargeted metabolomics analysis alone. Regulation of lipid metabolism in response to freezing is largely unknown in Dendrobium. In this study, a multi-omics strategy was used to offer a better means of studying metabolic flow during FT and FR. To this end, 6976 proteins were identified by the 4D_label-free proteome, including 5343 quantified proteins. For each of the two conditions, we enriched differentially accumulated proteins (DAPs) into 15 gene ontology (GO) terms, including primary metabolism, lipid metabolism, and photosynthesis processes. We also identified 7 lipid categories and 3672 lipid species using lipidome assays. We found significant remodeling occurring in the phospholipid category during FT and FR. We also found that most sphingolipids were significantly upregulated. An integrated multi-omics analysis revealed significant changes in the expression levels of 141 mRNAs and encoding proteins under both FT and FR conditions. During FT, phospholipase A (PLA) and phospholipase D (PLD) were associated with phospholipid editing and galactolipid remodeling. These results provide valuable new insights into how the freezing tolerance of D. catenatum might be improved by genetic engineering.

A Multi-Center, Prospective Observational Study to Investigate the Safety, Compliance, and Efficacy of Omethyl QTlet Soft Capsule.

Omega-3 fatty acids have been shown to be effective in lowering triglyceride (TG) levels; however, tolerability issues arise due to the large size of the pills. The purpose of this study was to examine the safety, compliance, and efficacy of Omethyl QTlet soft capsules (OQCs). This multi-center, prospective, observational study evaluated the safety, compliance, and efficacy of OQCs. Patients with hypertriglyceridemia with a history of omega-3 fatty acid intake were enrolled in this study and were prescribed OQCs (2 g−4 g/day) for eight weeks. All adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs) were recorded for safety evaluation. Adherence to treatment was assessed using questionnaires, and efficacy was assessed by changes in lipid and lipoprotein levels after eight weeks from baseline. The convenience of taking medication was analyzed for 580 patients, and the efficacy test was performed for 563 patients. The AE and ADR rates were 8.2% and 5.7%, respectively. There were only two SAEs. Of the patients, 55.8% responded that the OQC improved medication convenience, and mean changes in TG, total cholesterol, LDL-C, and non-HDL-C from baseline to eight weeks were −37.88 mg/dL, −11.56 mg/dL, −5.55 mg/dL, and −10.87 mg/dL, respectively (p-values < 0.001). In patients who had previously taken omega-3 fatty acids, OQCs showed safety and efficacy in lowering TG, and it was confirmed that compliance with medicine also improved compared to omega-3 fatty acids.

Abstract 13350: Accelerating the Diagnosis of Familial Hypercholesterolemia: A Mixed Methods Analysis of Physician-Patient Communication Needs

Introduction: Familial hypercholesterolemia (FH) is a common genetic disorder, but fewer than 10% are appropriately diagnosed. Use of electronic health records (EHRs) can potentially improve diagnosis and treatment. Hypothesis Systemwide strategies using the EHR can identify patients who may have FH with the goal of improving communication and preventive treatment. Methods: Our analysis included patients identified as having possible FH utilizing an LDL-C ≥190 mg/dL screen in the EHR. Patients were followed for 6 months, and lipid levels were measured at baseline, 6 weeks, 4 months, and 6 months. Changes in lipid levels were analyzed using paired sample t-tests for normalized data or Wilcoxon Rank Sum Test for skewed data. Our previously reported qualitative data were collected from 5 focus groups, 34 semi-structured key informant interviews, and open-ended survey items from patients and primary care clinicians before and after EHR messages about FH were sent. Results: In 12 patients, the LDL-C (25.3 ± 39.4 mg/dL, 18.7 ± 29.1%; p = 0.029) and total cholesterol/HDL-C (3.8 ± 1.0, 3.2 ± 0.9; p = 0.040) decreased at 4 months after lipid lower therapy initiation. In our previous work, which provides context to these findings, key themes identified were that patients trusted FH resources from the EHR and sought outside resources to educate themselves and their family, empower themselves, and improve their health. Yet, patients did not feel empowered due to the perceived lack of educational resources. Patients concluded that the physician-patient relationship via an EHR facilitates sustainable behavioral changes and treatment adherence. They also found that using the EHR to communicate with clinicians and to get laboratory results was helpful. Conclusion Leveraging the EHR to identify patients with FH can lead to better lipid management. Patients and clinicians can identify methods to improve diagnostic processes and communication channels in the EHR.

Polymorphisms of the apolipoprotein E gene affect response to atorvastatin therapy in acute ischemic stroke.

Polymorphisms of the apolipoprotein E (APOE) gene are related to the efficacy of statin therapy. The biological functions of the APOE subtypes determine the metabolism of blood plasma lipids and the progression of atherosclerosis. This study aimed to explore the impact of APOE gene polymorphisms on the effect of atorvastatin on lipid regulation and plaque stabilization. The study was a prospective cohort study that consecutively included patients with acute ischemic stroke (AIS) in the Department of Neurology, Shanghai Tenth People's Hospital, from December 2018 to December 2019. The patients were divided into E2, E3, and E4 groups according to their APOE genotype. Atorvastatin (20 mg) was administrated to all patients. Changes in blood lipid levels over 3 months and plaque size and stability over 12 months were analyzed. We enrolled 253 consecutive patients with AIS, of whom, 136 had carotid atherosclerotic plaques. Two patients with genotype E2/E4 were excluded. There were 30 patients in the E2 group (12.0%), 191 patients in the E3 group (76.0%), and 30 patients in the E4 group (12.0%). The lowest percentage reduction in low-density lipoprotein cholesterol (LDL-C) was observed in the E4 group (41.2%), while the highest percentage reduction was observed in the E2 group (17.6%). The plaques in the E2 group showed slower progression, while those in the E4 group showed more rapid progression. APOE gene polymorphisms affect the biological functions of atorvastatin. Compared to the ε3 or ε4 allele, the ε2 allele exerted a greater lipid-lowering effect on LDL-C levels, enhanced the ability of atorvastatin to stabilize carotid artery plaques, and slowed carotid artery plaque progression.

COMPARISON OF LIPID PARAMETERS IN MATERNAL SERUM AND NEWBORN CORD BLOOD

Background: One of the leading causes of morbidity and mortality in the modern period is coronary heart disease. The fetal origin concept has shown that the origins of this epidemic can be found as early as fetal life. A few research have compared the lipid profiles of cord blood from pre-term and term newborns, opening the door to early chronic disease prevention. Aim: The aim of the study was to compare lipid parameters in pre-term and term maternal serum and neonatal cord blood. Methods: In 300 newborns cord blood and 300 maternal serum samples, a cross-sectional research was performed. The placental side of the umbilical cord was used to collect cord blood samples, which were then examined for their lipid profiles, which included measurements of serum cholesterol, triglycerides, low density lipoprotein (LDL), high density lipoprotein (HDL), and apolipoproteins including ApoA and ApoB. Results: When lipid parameters from maternal serum and neonatal cord blood were compared, maternal serum had statistically significant higher values for the apolipoproteins, atherogenic index (AI), and lipid profile. Lipid parameters (TC, TG, LDL, very low density lipoprotein, Apolipoprotein B, and AI) were higher in mothers of pre-term babies and also in cord blood of pre-term neonates. Comparison of lipid parameters of pre-term and term mothers and neonatal cord blood was highly significant. Conclusion: There was a significant association of cord blood and maternal lipid parameters; hence, change in maternal lipid levels might influences the lipid levels in the cord blood of neonates.

Relationship Between Relative Grip Strength and Serum Total Cholesterol, High-Density Lipoprotein Cholesterol, Low-Density Lipoprotein Cholesterol, and Triglyceride Levels in Korean Middle-Aged or Older Adults: A Panel Regression Model.

Background: This study aimed to conduct panel data analysis to investigate the effects of relative grip strength on blood lipid levels according to sex and obesity levels in adults living in South Korea Methods: A total of 1015 middle-aged or older adults (40-94 years old), who participated in a chronic screening program conducted in Yangpyeong, Gyeonggi-do from 2007 to 2015, were included in this study. Grip strength was measured using a TKK-5401 dynamometer (Takei, Japan), and relative grip strength was calculated by dividing the absolute grip strength by body mass index (BMI, kg/m2). Blood lipids analyzed in this study included serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Random effect panel regression analysis was conducted to evaluate β values and 95% confidence intervals to investigate the independent effects of relative grip strength on blood lipid levels. Results: After adjusting for confounding variables, higher relative grip strength was associated with lower TG (β = -34.68, P < 0.001), TC (β = -8.47, P = 0.014), and LDL-C (β = -8.19, P = 0.012), and higher HDL-C (β = 6.70, P < 0.001). After additionally adjusting for BMI to evaluate the relationship between relative grip strength and blood lipid levels by obesity index, relative grip strength was only significantly associated with HDL-C (β = 5.03, P < 0.001). However, after adjusting for waist circumference, relative grip strength was significantly correlated with all blood lipid levels (TG: β = -33.31, P < 0.001; TC: β = -8.04, P = 0.021; LDL-C: β = -7.96, P = 0.015; and HDL-C: β = 6.73, P < 0.001). Differences in changes of blood lipid levels according to an increase in relative grip strength were observed about sex and obesity level. Conclusions: We observed that relative grip strength and blood lipid levels were associated, and increased muscular strength from regular resistance exercise could help to improve blood lipid levels in middle-aged or older adults.

LRRK2 and Lipid Pathways: Implications for Parkinson's Disease.

Genetic alterations in the LRRK2 gene, encoding leucine-rich repeat kinase 2, are a common risk factor for Parkinson's disease. How LRRK2 alterations lead to cell pathology is an area of ongoing investigation, however, multiple lines of evidence suggest a role for LRRK2 in lipid pathways. It is increasingly recognized that in addition to being energy reservoirs and structural entities, some lipids, including neural lipids, participate in signaling cascades. Early investigations revealed that LRRK2 localized to membranous and vesicular structures, suggesting an interaction of LRRK2 and lipids or lipid-associated proteins. LRRK2 substrates from the Rab GTPase family play a critical role in vesicle trafficking, lipid metabolism and lipid storage, all processes which rely on lipid dynamics. In addition, LRRK2 is associated with the phosphorylation and activity of enzymes that catabolize plasma membrane and lysosomal lipids. Furthermore, LRRK2 knockout studies have revealed that blood, brain and urine exhibit lipid level changes, including alterations to sterols, sphingolipids and phospholipids, respectively. In human LRRK2 mutation carriers, changes to sterols, sphingolipids, phospholipids, fatty acyls and glycerolipids are reported in multiple tissues. This review summarizes the evidence regarding associations between LRRK2 and lipids, and the functional consequences of LRRK2-associated lipid changes are discussed.