Lipid Changes Research Articles

Prediction of motor and non-motor Parkinson’s disease symptoms using serum lipidomics and machine learning: a 2-year study

Identifying biological factors which contribute to the clinical progression of heterogeneous motor and non-motor phenotypes in Parkinson’s disease may help to better understand the disease process. Several lipid-related genetic risk factors for Parkinson’s disease have been identified, and the serum lipid signature of Parkinson’s disease patients is significantly distinguishable from controls. However, the extent to which lipid profiles are associated with clinical outcomes remains unclear. Untargeted high-performance liquid chromatography-tandem mass spectrometry identified >900 serum lipids in Parkinson’s disease subjects at baseline (n = 122), and the potential for machine learning models using these lipids to predict motor and non-motor clinical scores after 2 years (n = 67) was assessed. Machine learning models performed best when baseline serum lipids were used to predict the 2-year future Unified Parkinson’s disease rating scale part three (UPDRS III) and Geriatric Depression Scale scores (both normalised root mean square error = 0.7). Feature analysis of machine learning models indicated that species of lysophosphatidylethanolamine, phosphatidylcholine, platelet-activating factor, sphingomyelin, diacylglycerol and triacylglycerol were top predictors of both motor and non-motor scores. Serum lipids were overall more important predictors of clinical outcomes than subject sex, age and mutation status of the Parkinson’s disease risk gene LRRK2. Furthermore, lipids were found to better predict clinical scales than a panel of 27 serum cytokines previously measured in this cohort (The Michael J. Fox Foundation LRRK2 Clinical Cohort Consortium). These results suggest that lipid changes may be associated with clinical phenotypes in Parkinson’s disease.

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial

BackgroundTreatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.MethodsIn this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR.ResultsWe studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms.ConclusionsBoth treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT.Trial registrationClinicalTrials.gov ID NCT02374021.

The impact of heat stress on the human plasma lipidome.

The year of 2023 displayed the highest average global temperatures since it has been recorded-the duration and severity of extreme heat are projected to increase. Rising global temperatures represent a major public health threat, especially to occupations exposed to hot environments, such as construction and agricultural workers, and first responders. Despite efforts of the scientific community, there is still a need to characterize the pathophysiological processes leading to heat related illness and develop biomarkers that can predict its onset. Here, we performed a plasma lipidomic analysis on male and female subjects who underwent heat tolerance testing (HTT), consisting of a 2-h treadmill walk at 5 km/h with 2% inclination at a controlled temperature of 40°C. We identified 995 lipids from 27 classes, with nearly half of all detected lipids being responsive to HTT. Lipid classes related to substrate utilization were predominantly affected by HTT, with a downregulation of triacylglycerols and upregulation of free fatty acids and acyl-carnitines (CARs). We additionally examined correlations between changes in plasma lipids by using the physiological strain index (PSI). Here, even chain CAR 4:0, 14:0 and 16:1, suggested by-products of incomplete beta oxidation, and diacylglycerols displayed the highest correlation to PSI. PSI did not correlate with plasma lactate levels, suggesting that correlations between even chain CARs and PSI is related to metabolic efficiency versus physical exertion. Overall, our results show that HTT has a strong impact on the plasma lipidome and that metabolic inefficiencies may underlie heat intolerance.

Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity

BackgroundDiabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation. MethodsA comprehensive lipidomic analysis of different lipid groups, were performed on liver tissue and plasma samples obtained at the time of histology from a well-defined cohort of 72 MASLD participants. The lipid profiles of controls were compared to those of MASLD patients with obesity, diabetes, or a combination of both. ResultsMASLD patients without obesity or diabetes exhibited distinct changes in the lipid profile of their liver tissue. The presence of diabetes or obesity further modified these lipid profiles (e.g., ceramide 47:7;4O), with positive or negative correlation (p < 0.05). A step-wise increase (long-chain fatty acids, triglycerides, and ceramides) or decrease (ultra-long fatty acids, diglycerides, and phospholipids) for lipid groups was observed compared to control among patients with MASLD without obesity or diabetes to MASLD patients with obesity as a single risk factor, and MASLD patients with obesity and diabetes. Changes in lipids observed in the plasma did not align with their corresponding liver tissue findings. ConclusionThe changes observed in the composition of lipids are not similar in patients with obesity and diabetes among those with MASLD. This highlights the different metabolic processes at play. The presence of obesity or diabetes in patients with MASLD exacerbates these lipid derangements, underscoring the potential for targeted intervention in MASLD patients.

Investigation of the structural changes in the hippocampus and prefrontal cortex using FTIR spectroscopy in sleep deprived mice

Sleep is a basic, physiological requirement for living things to survive and is a process that covers one third of our lives. Melatonin is a hormone that plays an important role in the regulation of sleep. Sleep deprivation affect brain structures and functions. Sleep deprivation causes a decrease in brain activity, with particularly negative effects on the hippocampus and prefrontal cortex. Despite the essential role of protein and lipids vibrations, polysaccharides, fatty acid side chains functional groups, and ratios between amides in brain structures and functions, the brain chemical profile exposed to gentle handling sleep deprivation model versus Melatonin exposure remains unexplored. Therefore, the present study, aims to investigate a molecular profile of these regions using FTIR spectroscopy measurement’s analysis based on lipidomic approach with chemometrics and multivariate analysis to evaluate changes in lipid composition in the hippocampus, prefrontal regions of the brain. In this study, C57BL/6J mice were randomly assigned to either the control or sleep deprivation group, resulting in four experimental groups: Control (C) (n = 6), Control + Melatonin (C + M) (n = 6), Sleep Deprivation (S) (n = 6), and Sleep Deprivation + Melatonin (S + M) (n = 6). Interventions were administered each morning via intraperitoneal injections of melatonin (10 mg/kg) or vehicle solution (%1 ethanol + saline), while the S and S + M groups underwent 6 h of daily sleep deprivation from using the Gentle Handling method. All mice were individually housed in cages with ad libitum access to food and water within a 12-hour light–dark cycle. Results presented that the brain regions affected by insomnia. The structure of phospholipids, changed. Yet, not only changes in lipids but also in amides were noticed in hippocampus and prefrontal cortex tissues. Additionally, FTIR results showed that melatonin affected the lipids as well as the amides fraction in cortex and hippocampus collected from both control and sleep deprivation groups.

Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials.

Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size. Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05. This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; P < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; P < 0.00001) compared to the placebo. BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.

Characterization of the plasma metabolome and lipidome in response to sleeve gastrectomy and gastric bypass surgeries reveals molecular patterns of surgical weight loss

ObjectivesBariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome. MethodsWe characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models. ResultsThere were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate. ConclusionsOur findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery.

Spatial metabolomics reveals key features of hippocampal lipid changes in rats with postoperative cognitive dysfunction.

Postoperative cognitive dysfunction (POCD) is a common complication after cardiac surgery. Numerous evidence suggest that dysregulation of lipid metabolism is associated with cognitive impairment; however, its precise role in the development of POCD is still obscure. In this study, we established a cardiopulmonary bypass (CPB) model in rats and employed the Barnes maze to assess cognitive function, selecting POCD rats for subsequent experimentation. Utilizing mass spectrometry imaging, we detected plenty of lipids accumulates within the hippocampal CA1in the POCD group. Immunofluorescence staining revealed a significant reduction in the fluorescence intensity of calcium-independent phospholipases A2 (iPLA2) in the POCD group compared to the control, while serine palmitoyl transferase (SPT) was markedly increased in the POCD group. Transmission electron microscopy revealed that the number of synapses in hippocampal CA1decreased significantly and postsynaptic density became thinner in POCD group. Furthermore, after reversing the metabolic disorders of iPLA2 and SPT in the rat brain with docosahexaenoic acid and myriocin, the incidence of POCD after CPB was significantly reduced and the disrupted lipid metabolism in the hippocampus was also normalized. These findings may offer a novel perspective for exploring the etiology and prevention strategies of POCD after CPB.

Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation.

Ezetimibe, which lowers cholesterol by blocking the intestinal cholesterol transporter Niemann-Pick C1 like 1, is reported to reduce hepatic steatosis in humans and animals. Here, we demonstrate the changes in hepatic metabolites and lipids and explain the underlying mechanism of ezetimibe in hepatic steatosis. We fed Otsuka Long-Evans Tokushima Fatty (OLETF) rats a high-fat diet (60kcal % fat) with or vehicle (control) or ezetimibe (10mgkg-1) via stomach gavage for 12 weeks and performed comprehensive metabolomic and lipidomic profiling of liver tissue. We used rat liver tissues, HepG2 hepatoma cell lines, and siRNA to explore the underlying mechanism. In OLETF rats on a high-fat diet, ezetimibe showed improvements in metabolic parameters and reduction in hepatic fat accumulation. The comprehensive metabolomic and lipidomic profiling revealed significant changes in phospholipids, particularly phosphatidylcholines (PC), and alterations in the fatty acyl-chain composition in hepatic PCs. Further analyses involving gene expression and triglyceride assessments in rat liver tissues, HepG2 hepatoma cell lines, and siRNA experiments unveiled that ezetimibe's mechanism involves the upregulation of key phospholipid biosynthesis genes, CTP:phosphocholine cytidylyltransferase alpha and phosphatidylethanolamine N-methyl-transferase, and the phospholipid remodeling gene lysophosphatidylcholine acyltransferase 3. This study demonstrate that ezetimibe improves metabolic parameters and reduces hepatic fat accumulation by influencing the composition and levels of phospholipids, specifically phosphatidylcholines, and by upregulating genes related to phospholipid biosynthesis and remodeling. These findings provide valuable insights into the molecular pathways through which ezetimibe mitigates hepatic fat accumulation, emphasizing the role of phospholipid metabolism.

Effect of alcohol consumption on lipid profile

Now-a-days alcoholism is major complication for development of different diseases. According to our literature review chronic alcoholic consumption will cause the lot of health complications. People without any comorbidities are also diagnosed with the lot of health complications at early age because of alcohol consumption. Our aim of the study is to identify the lipid changes in chronic alcoholic patients and how it effects on their health.To monitor the lipid changes in alcoholic persons.A prospective observational study was conducted for duration of six months, the data has been collected in 456 patients over six months of period and the data was collected with informed consent from the persons. All the data was collected by interacting with persons by using data collection form and laboratory reports were studied.In our study, 456 male populations were included. Out of 456 members, 272 people were alcoholics, and 184 members were non-alcoholic. Out of 272 population 180 are chronic alcoholics and 92 are occasional alcoholics. Out of 456 members young adults (18-25) 182 (39.9%) persons and old adults (26-40) were 274 (60%) persons296 members are taking alcohol with food and 160 members are taking without food. Out of 456 population 438 (96%) persons are non-vegetarians and 18(4%) members are vegetarians. Out of 272, 104 members were drinking beer, 58 were cheap liquor, 25 were Officers' choice, 18 were royal stag, 22 were blenders pride, 15 were signature, 23 were mixed brands, and 7 were others. In our study 156 persons were drinking sweetened beverages, 52(33.3%) members are daily beverage intakes and 104(33.3%) Members are occasionally beverage intakes. According to our study most commonly used sugary beverage brands are thumps up 93(59%), 48(31%) Sting,15(10%) other sugary beverages. Out of 156, Triglycerides were elevated in 47 and LDL was elevated in 36 persons, VLDL elevated in 4 persons and T. Cholesterol elevated in 5 members, Normal lipid profile in 64 persons. Out of 456 persons, 314(69%) are undiagnosed and 142(31%) are diagnosed with lipid changes. According to our common complications associated with alcohol consumption 39 were cardiac, 56 were hepatic, 9 were renal, and 38 were others (pancreatitis, stroke, cholelithiasis).In our study, we concluded that alcohol consumption will mainly affect triglyceride levels. Elevation of triglyceride levels is associated with the quantity and duration of alcohol intake. Normal Intake of alcohol does not cause lipid changes. Excessive intake of beer and cheap liquor increases TG. Excessive alcohol intake and fat intake will increase the LDL, Triglycerides, VLDL and decrease HDL. Excessive intake of sweetened beverages may also cause dyslipidaemia. Because it contains a high number of calories. The most common complication associated with elevation of triglycerides are hypertension, cardiovascular disease. Alcohol intake with food or without food shows the same complications but the absorption of alcohol may vary with food. Alcohol consumption with fat intake will cause hyperlipidaemia.

768-P: A Phase 1b/2a Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of PB-718, a GLP-1R/GCGR Dual Agonist in Subjects with Obesity

Introduction: PB-718 is a fixed dose combination of PB-119 (GLP-1 receptor agonist) and PB-722 (glucagon receptor agonist in clinical development. Compared with a single molecule approach, PB-718 may offer the balance between GLP-1 and GCGR through adjusting the molar ratio of PB-119 and PB-722 to achieve optimal efficacy and safety. Linear pharmacokinetics, good tolerability and promising effect of weight loss have been demonstrated in a phase 1 study conducted in US. Here we report a phase 1b/2a study in Obesity Methods: Thirty-six patients with obesity (BMI 30.5-40.0 kg/m2) without diabetes were randomized to this 3-sequential cohorts study (NCT06147544). In each cohort, 12 subjects were randomized (3:1) to receive PB-718 (PB-119/PB-722 600/1560 μg, 900/2340 μg or 1600/4160 μg) or placebo SC. injections once a week for 12-18 weeks. The primary endpoints were safety and PK profile. The secondary efficacy endpoints included changes in body weight (BW), BMI, lipids and HbA1c levels. Liver MRI-PDFF and body composition analysis were also assessed. Results: Both PB-119 and PB-722 demonstrated dose-proportional increases in AUC0-last and Cmax ,showing linear, and synergic pharmacokinetics. At 12 weeks, BW, FPG, HbA1c, Lipid, insulin level and HOMA-IR all decreased dose-dependently, and significant reduction in BW of over 4-6% were observed. Serum uric acid was also decreased. Liver fat content and visceral fat mass also showed significant and dose-related reduction with PB-718 treatment. Meanwhile, PB-718 groups lost more fat mass than lean mass. GI side effects were the most common AEs, and were all grade 1 in severity. Conclusions: PB-718 was safe, had predicted PK profile, and led to greater reductions in BW, HbA1c, blood lipids, uric acid, liver fat content and visceral fat mass. These data highlight the potential for PB-718 to provide additional benefit, and support the development of PB-718 as a promising treatment for obesity and NASH. Disclosure K. Ding: None.

Occupational noise and genetic variants in stress hormone biosynthesis-based genes and rates of blood lipid changes in China: A five-year longitudinal study

Lipid profiles are influenced by both noise and genetic variants. However, little is known about the associations of occupational noise and genetic variants with age-related changes in blood lipids, a crucial event in the initiation and evolution of atherosclerotic cardiovascular diseases. We aimed to evaluate the associations of blood lipid change rates with occupational noise and genetic variants in stress hormone biosynthesis-based genes. This cohort was established in 2012 and 2013 and was followed up until 2017. A total of 952 participants were included in the final analysis and all of them were categorized to two groups, the exposed group and control group, according to the exposed noise levels in their working area. Single nucleotide polymorphisms (SNPs) in stress hormone biosynthesis-based genes were genotyped. Five physical examinations were conducted from 2012 to 2017 and lipid measurements were repeated five times. The estimated annual changes (EACs) of blood lipid were calculated as the difference in blood lipid levels between any 2 adjacent examinations divided by their time interval (year). The generalized estimating equations for repeated measures analyses with exchangeable correlation structures were used to evaluate the influence of exposing to noise (versus being a control) and the SNPs mentioned above on the EACs of blood lipids. We found that the participants experienced accelerated age-related decline in high-density lipoprotein cholesterol (HDL-C) levels as they were exposed to noise (β = −0.38, 95% confidence interval (CI), −0.66 to −0.10, P = 0.007), after adjusting for work duration, gender, smoking, alcohol consumption, and pack-years. This trend was only found in participants with COMT-rs165815 TT genotype (β = −1.19, 95% CI, −1.80 to −0.58, P < 0.001), but not in those with the CC or CT genotypes. The interaction of noise exposure and rs165815 was marginally significant (Pinteraction = 0.010) after multiple adjustments. Compared with DDC-rs11978267 AA genotype carriers, participants carrying rs11978267 GG genotype had decreased EAC of triglycerides (TG) (β = −5.06, 95% CI, −9.07 to −1.05, P = 0.013). Participants carrying DBH-rs4740203 CC genotype had increased EAC of total cholesterol (TC) (β = 1.19, 95% CI, 0.06 to 2.33, P = 0.039). However, these findings were not statistically significant after multiple adjustments. These results indicated that Occupational noise exposure was associated with accelerated age-related decreases in HDL-C levels, and the COMT-rs165815 genotype appeared to modify the effect of noise exposure on HDL-C changes among the occupational population.

Lipids balance as a spectroscopy marker of diabetes. Analysis of FTIR spectra by 2D correlation and machine learning analyses

The number of people suffering from type 2 diabetes has rapidly increased. Taking into account, that elevated intracellular lipid concentrations, as well as their metabolism, are correlated with diminished insulin sensitivity, in this study we would like to show lipids spectroscopy markers of diabetes. For this purpose, serum collected from rats (animal model of diabetes) was analyzed using Fourier Transformed Infrared-Attenuated Total Reflection (FTIR-ATR) spectroscopy. Analyzed spectra showed that rats with diabetes presented higher concentration of phospholipids and cholesterol in comparison with non-diabetic rats. Moreover, the analysis of second (IInd) derivative spectra showed no structural changes in lipids. Machine learning methods showed higher accuracy for IInd derivative spectra (from 65 % to 89 %) than for absorbance FTIR spectra (53–65 %). Moreover, it was possible to identify significant wavelength intervals from IInd derivative spectra using random forest-based feature selection algorithm, which further increased the accuracy of the classification (up to 92 % for phospholipid region). Moreover decision tree based on the selected features showed, that peaks at 1016 cm−1 and 2936 cm−1 can be good candidates of lipids marker of diabetes.

Mitochondrial injury induced by triclopyr in the rat liver

The herbicide triclopyr (3,5,6-trichloro-2-pyridinyloxyacetic acid) is already considered an environmental problem due to damage caused by incorrect disposal, leaching, and aerial dispersion, which may pose risks to the environment and human health. Studies have evaluated metabolism, absorption, excretion, and active transport but there is no clear information about its mode of action (MoA) and its cytotoxic action potential remains unknown. In this context, mitochondria have been used to assess the toxicity of xenobiotics, for this reason, to identify the toxic mechanism of triclopyr, hepatic mitochondria from Wistar rats were exposed in vitro to different concentrations of triclopyr (0.5–500 µM). There was neither formation/accumulation of reactive oxygen and nitrogen species, nor lipid peroxidation or changes in the mitochondrial antioxidant system, in addition to proper functioning of oxidative phosphorylation and ATP production. Changes were found in NAD(P)H oxidation, membrane potential dissipation and mitochondrial calcium gradient. These results demonstrate that mitochondria suffer damage related to their bioenergetics and redox status but not to their structure when exposed to concentrations of triclopyr considered higher than those described as found in the environment so far. Highlights Triclopyr has a low mitochondrial uncoupling potential. The damage caused to the bioenergetics and redox state of the mitochondria is related to concentrations considered higher than those found in the environment. Even at high concentrations, triclopyr was not able to change the structure of the organelle after exposure. Oxidative phosphorylation and ATP production were not impaired after exposure. NAD(P)H oxidation resulted in potential membrane dissipation and mitochondrial calcium gradient dissipation. Triclopyr does not have RONS-forming properties, as well as it does not peroxide membrane lipids, it preserves membrane sulfhydryl groups and maintains the normality of the GSH/GSSG ratio.

Implementation of Modern Therapeutic Drug Monitoring and Lipidomics Approaches in Clinical Practice: A Case Study with Colistin Treatment.

Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer's disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from Pseudomonas aeruginosa-induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 μg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.

Lipidomics and transcriptomics analysis revealed the role of the spleen of Nile tilapia (Oreochromis niloticus) in lipid metabolism

In fish, the development of the spleen is not as perfect as that of higher vertebrates, but it has the same functions that the spleen should have. Up to date, research on fish spleen is mostly focused on its immune function, and the roles and mechanisms of spleen in the regulation of fish metabolism are still unclear. For this purpose, we established a spleen-deficient model of Nile tilapia (Oreochromis niloticus) by splenectomy and integrated lipidomics and transcriptomics to study the changes and mechanisms of lipid metabolism in splenectomy tilapia so as to understand the effect of spleen on lipid metabolism in tilapia. We found that splenectomy can lead to lipid deposition in the liver of tilapia, significant changes in liver and serum lipid mass spectrometry, abnormal lipid metabolism, decreased anti-oxidative stress ability, and being more prone to lipid toxicity and fatty liver. Combined with the results of transcriptomics, we found that splenectomy resulted in down-regulation of differentially expressed genes in “cellular iron ion homeostasis,” “extracellular region,” “small molecule binding,” and “TGF-beta signaling pathway,” and iron metabolism-related genes such as tfa, bmp2b, bmp6, hamp, and slc40a1, etc. were closely related to differential lipid changes. Therefore, it is speculated that the abnormal lipid metabolism in tilapia after splenectomy is closely related to iron metabolism, and its molecular mechanism may be related to the hepcidin regulatory pathway—BMP-SMAD signaling pathway. This study can provide a new understanding of the relationship and mechanism between immune and nutritional metabolism in fish and also provide new ideas for the study of fish hepatic diseases.

High coverage of targeted lipidomics revealed lipid changes in the follicular fluid of patients with insulin-resistant polycystic ovary syndrome and a positive correlation between plasmalogens and oocyte quality.

Polycystic ovary syndrome with insulin resistance (PCOS-IR) is the most common endocrine and metabolic disease in women of reproductive age, and low fertility in PCOS patients may be associated with oocyte quality; however, the molecular mechanism through which PCOS-IR affects oocyte quality remains unknown. A total of 22 women with PCOS-IR and 23 women without polycystic ovary syndrome (control) who underwent in vitro fertilization and embryo transfer were recruited, and clinical information pertaining to oocyte quality was analyzed. Lipid components of follicular fluid (FF) were detected using high-coverage targeted lipidomics, which identified 344 lipid species belonging to 19 lipid classes. The exact lipid species associated with oocyte quality were identified. The number (rate) of two pronuclear (2PN) zygotes, the number (rate) of 2PN cleaved embryos, and the number of high-quality embryos were significantly lower in the PCOS-IR group. A total of 19 individual lipid classes and 344 lipid species were identified and quantified. The concentrations of the 19 lipid species in the normal follicular fluid (control) ranged between 10-3 mol/L and 10-9 mol/L. In addition, 39 lipid species were significantly reduced in the PCOS-IR group, among which plasmalogens were positively correlated with oocyte quality. This study measured the levels of various lipids in follicular fluid, identified a significantly altered lipid profile in the FF of PCOS-IR patients, and established a correlation between poor oocyte quality and plasmalogens in PCOS-IR patients. These findings have contributed to the development of plasmalogen replacement therapy to enhance oocyte quality and have improved culture medium formulations for oocyte in vitro maturation (IVM).

Rapid profiling of fish cell nitrogen metabolism with single-cell Raman spectroscopy: Unveiling enzyme's role in ammonia detoxification

Ammonia is a prevalent aquatic pollutant that disrupts cellular functions and energy metabolism in fish, posing significant environmental and health threats. This research investigates the critical role of arginase 2 (ARG2) in mitigating ammonia toxicity in fish cells and its implications in adapting to nitrogen metabolism under high ammonia exposure. Through a CRISPR-Cas9 engineered ARG2 knockdown (KD) in the Epithelioma Papulosum Cyprini (EPC) cell line, we first investigated the biochemical responses of ARG2 KD and wild-type (WT) EPC cells to ammonia stress (NH4Cl treatment), showing diminished urea production and decreased cell viability in ARG2 KD cells. Subsequently, single-cell Raman spectroscopy analysis revealed that ARG2 KD cells exhibited profound metabolic shifts, including changes in protein, nucleic acids, lipid and sugar levels, showing the adjusting role of ARG2 in the balance of carbohydrate and nitrogen metabolism. Furthermore, the upregulated responses of various amino acids, such as glutamine, arginine, alanine, glutamic acid, glycine, histidine, phenylalanine and valine, in WT cells after NH4Cl treatment diminished in ARG2 KD cells except for the decrease in aspartic acid, indicating a switching effect of ARG2 in nitrogen metabolism under ammonia stress. This study highlights ARG2's essential role in ammonia detoxification and emphasizes ARG2's protective function and its importance in metabolism, shedding light on the adaptive mechanisms fish cells deploy against high ammonia environments. These insights contribute to deep understanding of aquatic organisms' molecular responses to environmental ammonia pollution, offering potential strategies for their protection.

Modulation of oxidative stress and apoptosis by alteration of bioactive lipids in the pancreas, and effect of zinc chelation in a rat model of Alzheimer's disease

IntroductionIncreasing epidemiological evidence highlights the association between systemic insulin resistance and Alzheimer's disease (AD). It is known that peripheral insulin resistance in the early stages of AD precedes and is a precursor to amyloid-β (Aβ) deposition. Although it is known that improving the CNS insulin sensitivity of AD patients is an important therapeutic goal and that the majority of insulin in the brain comes from the periphery, there has been little attention to the changes that occur in the pancreatic tissue of AD patients. Therefore, it is crucial to elucidate the mechanisms affecting insulin resistance in pancreatic tissue in AD. It is known that zinc (Zn2+) chelation is effective in reducing peripheral insulin resistance, cell apoptosis, cell death, and oxidative stress. ObjectiveIt was aimed to determine the changes in bioactive lipids, amylin (AIPP), oxidative stress and apoptosis in pancreatic cells in the early stages of Alzheimer's disease. The main aim is to reveal the therapeutic effect of the Cyclo-Z agent on these changes seen in the pancreas due to AD disease. MethodsAD and ADC rats were intracerebroventricular (i.c.v.) Aβ1–42 oligomers. Cyclo-Z gavage was applied to ADC and SHC rats for 21 days. First of all, the effects of AIPP, bioactive ceramides, apoptosis and oxidative stress on the pancreatic tissue of AD group rats were evaluated. Then, the effect of Cyclo-Z treatment on these was examined. ELISA kit was used in biochemical analyses. ResultsAIPP and ceramide (CER) levels and CER/ sphingosine-1 phosphate (S1P) ratio were increased in the pancreatic tissue of AD rats. It also increased the level of CER kinase (CERK), which is known to increase the concentration of CER 1-phosphate (C1P), which is known to be toxic to cells in the presence of excessive CER concentration. Due to the increase in CER level, it was observed that apoptosis and oxidative stress increased in the pancreatic cells of AD group rats. ConclusionCyclo-Z, which has Zn2+ chelating properties, reduced AD model rats' AIPP level and oxidative stress and could prevent pancreatic apoptosis. Similar therapeutic effects were not observed in the pancreatic tissue of Cyclo-Z administered to the SH group. For this reason, it is thought that Cyclo-Z agent may have a therapeutic effect on the peripheral hyperinsulinemia observed in the early stages of AD disease and the resulting low amount of insulin transported to the brain, by protecting pancreatic cells from apoptosis and oxidative stress by regulating their bioactive metabolites.

Effect of radio frequency roasting on the lipid profile of peanut oil and the mechanism of lipids transformation: Revealed by untargeted lipidomics approach

Radio frequency (RF) heating has been proved an alternative roasting method for peanuts, which could effectively degrade aflatoxins and possesses the advantages of greater heating efficiency and penetration depth. This study aimed to investigate the influences of RF roasting on the lipid profile of peanut oil under 150 °C target temperature with varied peanut moisture contents (8.29 % and 20 %) and holding times (0, 7.5, and 15 min), using ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)-based lipidomics. In total, 2587 lipid species from 35 subclasses were identified. After roasting, the contents of sterol lipid (ST) and subclasses of glycerophospholipids (GPs) and glycoglycerolipids increased significantly, while fatty acid (FA), Oxidized (Ox-) FA, cholesterol (CE), and all subclasses of glycerolipids (GLs) decreased, and 1084 differential lipids were screened. The highest ST and lowest CE contents in peanut oil were achieved by medium roasting (7.5 min). The raise in moisture content of peanut simply affected a few GPs subclasses adversely. Compared with hot air (HA) roasting, RF decelerated lipid oxidation, showing higher levels of diacylglycerol, triacylglycerol and FA, with no additional negative impact and only 69 exclusive differential lipids. During RF roasting, hydrolysis and oxidation of fatty acyl chains into secondary oxides were the central behaviors of lipids transformation. This study could provide insights into the lipid changes and transformation mechanism of peanut oil by RF roasting processing.