BACKGROUND: Observational studies have indicated that the plasma lipid profiles of patients with atopic dermatitis show significant differences compared to healthy individuals. However, the causal relationship between these differences remains unclear due to the inherent limitations of observational studies. Our objective was to explore the causal effects between 179 plasma lipid species and atopic dermatitis, and to investigate whether circulating inflammatory proteins serve as mediators in this causal pathway.
METHODS: We utilized public genome-wide association studies data to perform a bidirectional two-sample, two-step mendelian randomization study. The inverse variance-weighted method was adopted as the primary analysis technique. MR-Egger and the weighted median were used as supplementary analysis methods. MR-PRESSO, Cochran\'s Q test, and MR-Egger intercept test were applied for sensitivity analyses to ensure the robustness of our findings.
RESULTS: The Mendelian randomization analysis revealed that levels of Phosphatidylcholine (PC) (18:1_20:4) (OR: 0.950, 95% CI: 0.929-0.972, p = 6.65 × 10- 6), Phosphatidylethanolamine (O-18:1_20:4) (OR: 0.938, 95% CI: 0.906-0.971, p = 2.79 × 10- 4), Triacylglycerol (TAG) (56:6) (OR: 0.937, 95% CI: 0.906-0.969, p = 1.48 × 10- 4) and TAG (56:8) (OR: 0.918, 95% CI: 0.876-0.961, p = 2.72 × 10- 4) were inversely correlated with the risk of atopic dermatitis. Conversely, PC (18:1_20:2) (OR: 1.053, 95% CI: 1.028-1.079, p = 2.11 × 10- 5) and PC (O-18:1_20:3) (OR: 1.086, 95% CI: 1.039-1.135, p = 2.47 × 10- 4) were positively correlated with the risk of atopic dermatitis. The results of the reverse directional Mendelian randomization analysis indicated that atopic dermatitis exerted no significant causal influence on 179 plasma lipid species. The level of circulating IL-18R1 was identified as a mediator for the increased risk of atopic dermatitis associated with higher levels of PC (18:1_20:2), accounting for a mediation proportion of 9.07%.
CONCLUSIONS: Our research suggests that plasma lipids can affect circulating inflammatory proteins and may serve as one of the pathogenic factors for atopic dermatitis. Targeting plasma lipid levels as a treatment for atopic dermatitis presents a potentially novel approach.

The elderly population is at a higher risk of cardiovascular complications, and dyslipidemia plays a significant role as a contributing factor. Chronic kidney disease (CKD) patients are prone to lipid abnormalities, further increasing the risk of cardiovascular complications. We aimed to investigate the lipid profile characteristics of the middle-aged and elderly population, particularly CKD patients. We conducted a cross-sectional study using baseline data from the Systolic Blood Pressure Intervention Trial (SPRINT). It was examined how lipid profiles are affected by age within the general population, and how BMI and lipid characteristics are affected by CKD subtype. Among 8746 participants, we observed a decreasing trend in LnTAG (natural logarithm of Triacylglycerol) and total Cholesterol (CHR) levels with increasing age, while high-density lipoprotein cholesterol (HDL-C) levels increased with age. In the CKD and non-CKD subgroups created through propensity score matching based on age, sex, and race, CKD individuals exhibited significantly higher average LnTAG levels across all age groups compared to the non-CKD group. Multivariable linear regression analysis, controlling for confounding variables, revealed a negative correlation between LnTAG and estimated glomerular filtration rate (eGFR) (r = -0.002, p < 0.001). HDL-C showed a positive correlation with eGFR (r = 0.057, p < 0.001). That is, in the middle-aged and elderly population, age demonstrated a negative correlation with total CHR and TAG levels, while exhibiting a positive correlation with HDL-C levels. CKD patients exhibited relatively higher TAG levels, which were positively associated with CKD progression.

BACKGROUND: Accumulating data on the associations between food consumption and lipid composition in the body is essential for understanding the effects of dietary habits on health.
OBJECTIVE: As part of omics research in the Tohoku Medical Megabank Community-Based Cohort Study, this study sought to reveal the dietary impact on plasma lipid concentration in a Japanese population.
METHODS: We conducted a correlation analysis of food consumption and plasma lipid concentrations measured using mass spectrometry, for 4032 participants in Miyagi Prefecture, Japan.
RESULTS: Our analysis revealed 83 marked correlations between six food categories and the concentrations of plasma lipids in nine subclasses. Previously reported associations, including those between seafood consumption and omega-3 fatty acids, were validated, while those between dairy product consumption and odd-carbon-number fatty acids (odd-FAs) were validated for the first time in an Asian population. Further analysis suggested that dairy product consumption is associated with odd-FAs via sphingomyelin (SM), which suggests that SM is a carrier of odd-FAs. These results are important for understanding odd-FA metabolism with regards to dairy product consumption.
CONCLUSIONS: This study provides insight into the dietary impact on plasma lipid concentration in a Japanese population.

BACKGROUND: Studies have shown that lipid-related indicators are associated with testosterone deficiency. However, it is difficult to determine which indicator is the most accurate predictor of testosterone deficiency. We aimed to identify the lipid-related indicators most predictive of testosterone deficiency in adults in the United States.
METHODS: This observational research was conducted on a population aged ≥ 20 years. By plotting the receiver operating characteristic curve (ROC) and obtaining the corresponding area under the curve (AUC) value, we assessed the predictive capacity of TyG, WTI, LAP, and VAI for testosterone deficiency. We compared the area under the curve (AUC) values of these measures to determine if there were any statistically significant differences. The relationship between lipid-related indices and testosterone hormones was investigated using regression modeling, eXtreme Gradient Boosting (XGBoost) modeling, and sensitivity analysis.
RESULTS: A total of 3,272 eligible participants were included in the study. Testosterone deficiency was found to exist in 20.63% of the participants. Subjects with higher lipid-related markers were more likely to have lower testosterone levels. LAP was the best predictor of testosterone deficiency in ROC analysis over other indicators (AUC = 0.7176, (95% CI: 0.6964-0.7389)).
CONCLUSIONS: LAP is the most straightforward and convenient indicator for identifying testosterone deficiency in clinical practice.

OBJECTIVE: Heart failure with preserved ejection fraction (HFpEF) is a multifactorial, multisystemic syndrome that involves alterations in lipid metabolism. This study aimed to test whether distinct plasma lipid profiles or lipid entities or both are associated with clinical and functional echocardiographic parameters in HFpEF.
RESULTS: We examined the human plasma lipidome in HFpEF patients (n = 18) with left ventricular ejection fraction ≥50% and N-terminal pro-brain natriuretic peptide (NT-proBNP) >125 pg/mL and control subjects (n = 12) using mass spectrometry-based shotgun lipidomics. The cohort included 8 women and 22 men with average age of 67.8 ± 8.6 SD. The control and disease groups were not significantly different with respect to age, body mass index, systolic and diastolic blood pressure, and waist-to-hip ratio. The disease group experienced more fatigue (P < 0.001), had more often coronary artery disease (P = 0.04), and received more medications (beta-blockers, P < 0.001). The disease group had significantly different levels of HFpEF-relevant parameters, including NT-proBNP (P < 0.001), left ventricular mass index (P = 0.005), left atrial volume index (P = 0.001), and left ventricular filling index (P < 0.001), and lower left ventricular end-diastolic diameter (P = 0.014), with no difference in left ventricular ejection fraction. Significant differences in lipid profiles between HFpEF patients and controls could not be detected, including no significant differences in abundance of circulating lipids binned by carbon chain length or by double bonds, nor at the level of individual lipid species. However, there was a striking correlation between selected lipids with smoking status that was independent of disease status, as well as between specific lipids and hyperlipidaemia [with corresponding significance of either false discovery rate (FDR) <0.1 or FDR < 0.01]. In an exploratory network analysis of correlations, we observed significantly stronger correlations within the HFpEF group between individual lipids from the cholesterol ester and phosphatidylcholine (PC) classes and clinical/echocardiographic parameters such as left atrial volume index, left ventricular end-diastolic diameters, and heart rate (FDR < 0.1). In contrast, the control group showed significantly stronger negative correlations (FDR < 0.1) between individual species from the PC and sphingomyelin classes and left ventricular mass index or systolic blood pressure.
CONCLUSIONS: We did not find significant direct associations between plasma lipidomic parameters and HFpEF and therefore could not conclude that any specific lipids are biomarkers of HFpEF. The validation in larger cohort is needed to confidently conclude the absence of first-order associations.

Kiwifruit contain many components, some considered beneficial, such as vitamins, phytochemicals and dietary fibre, and others potentially harmful, such as fructose and glucose in fruit sugars. In a 6-week, randomised, crossover study aimed at exploring the net effects of daily consumption of kiwifruit, 23 healthy participants consumed two Actinidia chinensis var. chinensis \'Zesy002\' (marketed as Zespri™ SunGold™ Kiwifruit) per day as part of their customary diet (intervention) or without kiwifruit (control) as their customary diet for 6 weeks in a cross-over study. Anthropometric data, venous blood, and urine samples were collected at the start and end of the 6-week intervention and control periods for the measurement of physical changes, plasma glucose, insulin, glycated haemoglobin, short-chain fatty acids, blood lipids, uric acid, inflammatory biomarkers, and urinary ascorbic acid. Variables were measured between the start and finish of interventions, and between intervention and control periods. Food diaries were completed on the 3 days before blood sampling to estimate dietary ascorbic acid and dietary fibre intakes. Despite urinary vitamin C and food diaries indicating compliance, and good precision in measurements, there were no appreciable changes in biomarkers during the study, either within or between intervention and control periods, that would indicate a change in health status. Thus, the sizes of any effects of kiwifruit ingestion were too small to become significant under the test conditions used, indicating a high probability that daily ingestion of two SunGold kiwifruit is safe with respect to metabolic health.

UNASSIGNED: To assess the prevalence, pattern, and associated factors of dyslipidemia in patients with coronary artery disease (CAD) in the Northwest region of Pakistan.
UNASSIGNED: A cross-sectional secondary data analysis was performed on CAD patients visiting cardiology clinics in selected hospitals from July to December 2019. A total of 362 patients were included via consecutive sampling. Dyslipidemia was operationalized according to the \"National Cholesterol Education Program (NCEP ATP III) guidelines\".
UNASSIGNED: Mixed dyslipidemia was recorded in 92.26% of the patients, while isolated dyslipidemia was observed in 5.24%. A high prevalence of combined dyslipidemia with increased LDL-C, TG, and low HDL-C was noted. Contrarily, elevated LDL-C was the commonest single lipid disorder (84.25%). Hypercholesterolemia was the least common disorder. Increasing BMI was found to be independently associated with hypercholesterolemia (OR: 1.19). Similarly, age (OR: 0.97) and being a rural resident (OR: 2.61) were independent factors associated with hypertriglyceridemia. Furthermore, being an urban resident (OR: 2.25) and increasing BMI (OR: 1.77) were also significantly associated with high LDL-C.
UNASSIGNED: Mixed dyslipidemias were observed in the majority of the patients. Age, BMI, and residence were noted to be independently associated with abnormal lipids. Early screening and proper management should be encouraged to minimize this significant cardiovascular risk.

The expression of inflammation-related miRs bound to high-density lipoproteins (HDLs), the anti-inflammatory activity of HDLs isolated from individuals with breast cancer, and controls were determined. Forty newly diagnosed women with breast cancer naïve of treatment and 10 control participants were included. Cholesterol-loaded bone-marrow-derived macrophages were incubated with HDL from both groups and challenged with lipopolysaccharide (LPS). Interleukin 6 (IL6) and tumor necrosis factor (TNF) in the medium were quantified. The miRs in HDLs were determined by RT-qPCR. Age, body mass index, menopausal status, plasma lipids, and HDL composition were similar between groups. The ability of HDL to inhibit IL6 and TNF production was higher in breast cancer compared to controls, especially in advanced stages of the disease. The miR-223-3p and 375-3p were higher in the HDLs of breast cancer independent of the histological type of the tumor and had a high discriminatory power between breast cancer and controls. The miR-375-3p was greater in the advanced stages of the disease and was inversely correlated with the secretion of inflammatory cytokines. Inflammation-related miRs and the anti-inflammatory role of HDLs may have a significant impact on breast cancer pathophysiology.

Patients with non-alcoholic steatohepatitis (NASH) show significantly faster progress in the stages of fibrosis compared to those with non-alcoholic fatty liver (NAFL) disease. The non-invasive diagnosis of NASH remains an unmet clinical need. Preliminary data have shown that sphingolipids, especially ceramides, fatty acids, and other lipid classes may be related to the presence of NASH and the histological activity of the disease. The aim of our study was to assess the association of certain plasma lipid classes, such as fatty acids, acylcarnitines, and ceramides, with the histopathological findings in patients with NASH. The study included three groups: patients with NASH (N = 12), NAFL (N = 10), and healthy [non non-alcoholic fatty liver disease (NAFLD)] controls (N = 15). Plasma samples were collected after 12 h of fasting, and targeted analyses for fatty acids, acylcarnitines, and ceramides were performed. Baseline clinical and demographic characteristics were collected. There was no significant difference in baseline characteristics across the three groups or between NAFL and NASH patients. Patients with NASH had increased levels of several fatty acids, including, among others, fatty acid (FA) 14:0, FA 15:0, FA 18:0, FA 18:3n3, as well as Cer(d18:1/16:0), compared to NAFL patients and healthy controls. No significant difference was found between NAFL patients and healthy controls. In conclusion, patients with NASH exhibited a distinctive plasma lipid profile that can differentiate them from NAFL patients and non-NAFLD populations. More data from larger cohorts are needed to validate these findings and examine possible implications for diagnostic and management strategies of the disease.

Drug targets with genetic support are several-fold more likely to succeed in clinical trials. We introduce a genetic-driven approach based on causal inferences that can inform drug target prioritization, repurposing, and adverse effects of using lipid-lowering agents. Given that a multi-trait approach increases the power to detect meaningful variants/genes, we conduct multi-omics and multi-trait analyses, followed by network connectivity investigations, and prioritize 30 potential therapeutic targets for dyslipidemia, including SORT1, PSRC1, CELSR2, PCSK9, HMGCR, APOB, GRN, HFE2, FJX1, C1QTNF1, and SLC5A8. 20% (6/30) of prioritized targets from our hypothesis-free drug target search are either approved or under investigation for dyslipidemia. The prioritized targets are 22-fold higher in likelihood of being approved or under investigation in clinical trials than genome-wide association study (GWAS)-curated targets. Our results demonstrate that the genetic-driven approach used in this study is a promising strategy for prioritizing targets while informing about the potential adverse effects and repurposing opportunities.