Plasma Lipid Research Articles

Apolipoprotein E knockout, but not cholesteryl ester transfer protein (CETP)-associated high-density lipoprotein cholesterol (HDL-C) lowering, exacerbates muscle wasting in dysferlin-null mice

BackgroundDysferlin-deficient limb-girdle muscular dystrophy type 2B (Dysf) mice are notorious for their mild phenotype. Raising plasma total cholesterol (CHOL) via apolipoprotein E (ApoE) knockout (KO) drastically exacerbates muscle wasting in Dysf mice. However, dysferlinopathic patients have abnormally reduced plasma high-density lipoprotein cholesterol (HDL-C) levels. The current study aimed to determine whether HDL-C lowering can exacerbate the mild phenotype of dysferlin-null mice.MethodsHuman cholesteryl ester transfer protein (CETP), a plasma lipid transfer protein not found in mice that reduces HDL-C, and/or its optimal adapter protein human apolipoprotein B (ApoB), were overexpressed in Dysf mice. Mice received a 2% cholesterol diet from 2 months of age and characterized through ambulatory and hanging functional tests, plasma analyses, and muscle histology.ResultsCETP/ApoB expression in Dysf mice caused reduced HDL-C (54.5%) and elevated ratio of CHOL/HDL-C (181.3%) compared to control Dysf mice in plasma, but without raising CHOL. Compared to the severe muscle pathology found in high CHOL Dysf/ApoE double knockout mice, Dysf/CETP/ApoB mice did not show significant changes in ambulation, hanging capacity, increases in damaged area, collagen deposition, or decreases in cross-sectional area and healthy myofibre coverage.ConclusionsCETP/ApoB over-expression in Dysf mice decreases HDL-C without increasing CHOL or exacerbating muscle pathology. High CHOL or nonHDL-C caused by ApoE KO, rather than low HDL-C, likely lead to rodent muscular dystrophy phenotype humanization.

Lipid profile alterations and biomarker identification in type 1 diabetes mellitus patients under glycemic control

BackgroundType 1 diabetes mellitus (T1DM) is well-known to trigger a disruption of lipid metabolism. This study aimed to compare lipid profile changes in T1DM patients after achieving glucose control and explore the underlying mechanisms. In addition, we seek to identify novel lipid biomarkers associated with T1DM under conditions of glycemic control.MethodsA total of 27 adults with T1DM (age: 34.3 ± 11.2 yrs) who had maintained glucose control for over a year, and 24 healthy controls (age: 35.1 + 5.56 yrs) were recruited. Clinical characteristics of all participants were analyzed and plasma samples were collected for untargeted lipidomic analysis using mass spectrometry.ResultsWe identified 594 lipid species from 13 major classes. Differential analysis of plasma lipid profiles revealed a general decline in lipid levels in T1DM patients with controlled glycemic levels, including a notable decrease in triglycerides (TAGs) and diglycerides (DAGs). Moreover, these T1DM patients exhibited lower levels of six phosphatidylcholines (PCs) and three phosphatidylethanolamines (PEs). Random forest analysis determined DAG(14:0/20:0) and PC(18:0/20:3) to be the most prominent plasma markers of T1DM under glycemic control (AUC = 0.966).ConclusionsThe levels of all metabolites from the 13 lipid classes were changed in T1DM patients under glycemic control, with TAGs, DAGs, PCs, PEs, and FFAs demonstrating the most significant decrease. This research identified DAG(14:0/20:0) and PC(18:0/20:3) as effective plasma biomarkers in T1DM patients with controled glycemic levels.

Brown adipose tissue facilitates the fever response following infection with Salmonella enterica serovar Typhimurium in mice

Brown adipose tissue (BAT) combusts lipids and glucose to generate heat. Via this process of nonshivering thermogenesis, BAT plays a pivotal role in thermoregulation in cold environments, but its contribution to immune-induced fever is less clear. Male APOE∗3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism, and wild-type mice were given an intraperitoneal injection of Salmonella enterica serovar Typhimurium (S.tm). Energy expenditure and substrate utilization, plasma lipid levels, fatty acid (FA) uptake by adipose tissues, and lipid content and thermogenic markers in adipose tissues were examined. S.tm infection led to a set of characteristic symptoms, including elevated body temperature and decreased body weight. Whole-body energy expenditure was significantly decreased 72 h postinfection, but fat oxidation was increased and accompanied by a substantial reduction in plasma triglyceride (TG) levels as demonstrated in APOE∗3-Leiden.CETP mice. S.tm infection strongly increased uptake of FAs from TG-rich lipoproteins by BAT, which showed a positive correlation with body temperature in infected mice. Upon histological examination of BAT from wild-type or APOE∗3-Leiden.CETP mice, elevated levels of tyrosine hydroxylase were observed, indicative of stimulated sympathetic activity. In addition, the gene expression profile was consistent with more adrenergic stimulation, while lipid content was reduced. Furthermore, browning of white adipose tissue was observed, evidenced by a modest increase in TG-derived FA uptake, the presence of multilocular cells, and induction of uncoupling protein 1 expression. We proposed that BAT, or thermogenic adipose tissue in general, is involved in the maintenance of elevated body temperature upon invasive bacterial infection.

Role of inflammatory biomarkers in mediating the effect of lipids on spontaneous intracerebral hemorrhage: a two-step, two-sample Mendelian randomization study.

Spontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors. Employing a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results. The results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016-1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001-1.279, p = 0.049) were identified as significant mediators. This study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.

Abstract Tu120: Sarm1 promotes diabetic cardiomyopathy by regulating HIF signaling, lipotoxicity and mitochondrial dysfunction

Heart failure occurs at twice the rate in diabetic patients as compared to normal patients, and reduced NAD levels are associated with diabetic cardiomyopathy. Sterile Alpha and Tir Motif Containing 1 (SARM1) is an intracellular NAD hydrolase. We hypothesized that SARM1 promotes NAD decline and diabetic cardiomyopathy. We subjected wild type (WT) and global SARM1 knockout mice to chronic diabetic stress induced by streptozotocin injections. We showed that 16-week diabetic stress promoted progressive decline in systolic and diastolic function, and in NAD levels, which were ameliorated by SARM1 deficiency despite similar plasma glucose and lipid levels. Gene Module Network Analysis of cardiac transcriptomics identified upregulation of genes in fatty acid and glucose metabolic processes, and suppression of genes in mitochondrial processes in diabetic WT hearts. SARM1 deficiency reversed upregulated fatty acid metabolic genes but had no impact on glucose metabolic and mitochondrial gene expressions in diabetic hearts. By transmission electron microscopy and Oil Red O staining, we observed increases in lipid droplet sizes and lipid accumulation in diabetic WT hearts, which were suppressed by SARM1 deficiency. SARM1 deficiency did not reverse mitochondrial gene expression, but it mitigated the reduction in ADP-driven respiration, mitochondrial fragmentation, and abnormal cristae structure in diabetic WT hearts. Diabetic WT hearts had increased phospho-PDH and PDK4 levels as well as activated HIF signaling, exhibiting an increase in expression of HIF-1a target genes (55 genes) , many of which were related to lipid storage. SARM1 deficiency suppressed expression of HIF1-a target genes (53 genes) , and reduced phospho-PDH and PDK4 levels. These data suggest that SARM1 regulates pseudohypoxic HIF-dependent signaling in diabetic hearts. In summary, our current data support the hypothesis that SARM1 regulates HIF-dependent transcription events, particularly those influencing lipid metabolism of diabetic hearts. However, SARM1 promotes mitochondrial dysfunction in diabetic hearts independent of transcription of mitochondrial genes. Further studies will continue to elucidate the role of SARM1 in diabetic cardiomyopathy, and its potential as a novel therapeutic target.

Effects of MIND diet and propolis supplementation on metabolic syndrome indices and cognitive function among patients with metabolic syndrome in Isfahan, Iran, 2024. A rationale and study protocol for randomized controlled trial.

Metabolic syndrome (MetS) is the main general and clinical health challenge worldwide. Based on the National Cholesterol Education Program, if the person has three or more indices containing: elevated fasting blood sugar, high levels of triglycerides, hypertension, low levels of high-density lipoprotein cholesterol, and central obesity, he suffers MetS. The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay diet is a novel diet that with the specific aim of safeguarding cognitive function. Propolis is a resinous substance produced by bees from the combination of buds and secretions of plants with saliva and bee enzymes. After propolis supplementation, a significant reduction in fasting plasma glucose levels and lipid profiles has been observed. Considering the importance of chronic diseases like MetS on health, the role of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and propolis supplement that will improve blood sugar, blood lipid, anthropometric indicators, blood pressure, and cognitive function, and limited contradictory studies, we decided to conduct this study. This study, which is a randomized controlled clinical trial study, will be conducted on adults with MetS who will visit Hazrat Ali Health Center in Isfahan. Participants must provide informed consent before engaging in the study. Demographic data such as age, gender, and medical history will be recorded. Then, anthropometric indices, MetS indices, and cognitive function will be measured in all subjects. The study participants will be divided into three groups and will be controlled for 12 weeks. We will have a MIND diet + placebo group, a MIND diet + propolis supplement group, and a control group that will receive a microcrystalline cellulose placebo and usual dietary advice. At the end of the intervention, all indices will be assessed again. The data obtained in the study will be analyzed at descriptive and analytical levels by the statistical software SPSS26. The present study's protocol was approved by the Iranian Registry of Clinical Trials (www.irct.ir) on 3/28/2023 and a registration reference is IRCT20230105057054N1.

Dietary supplementation with 25-hydroxyvitamin D3 regulates productive performance, lipid metabolism and gut microbiota in aged laying ducks

The aim of this study was to investigate the effect of dietary supplementation with 25-hydroxyvitamin D3 (25(OH)D3) on productive performance, lipid metabolism and gut microbiota in aged laying ducks. A total of 432 healthy Longyan ducks at 60-week of age were randomly allotted to 6 groups, each with 6 replicates of 12 ducks. Ducks were given a basal diet (without added 25(OH)D3) or that diet supplemented with 800, 1600, 2400, 3200, or 4000 IU/kg 25(OH)D3 for a total of 16 wk. Dietary supplementation with 25(OH)D3 improved egg production, egg mass and average daily feed intake, and decreased the feed conversion ratio (FCR) of ducks during the whole trial period (linear, quadratic; P < 0.05). Supplementation with 25(OH)D3 decreased very low-density lipoprotein (VLDL) content in yolk (P = 0.008), decreased high-density lipoprotein and low-density lipoprotein (LDL) content in plasma (P = 0.002). Hepatic index, VLDL, LDL, triglyceride and total cholesterol content in liver, nonalcoholic fatty liver activity score of liver and alanine aminotransferase content in plasma were decreased with supplementation of 25(OH)D3 (linear or quadratic; P < 0.05). The decreased hepatic apolipoprotein B 100 and lipoprotein lipase expression, and increased hepatic peroxisome proliferator-activated receptor-α and sterol regulatory element binding protein-1 expression resulted from 25(OH)D3 supplementation (linear, quadratic; P < 0.05). Moreover, 25(OH)D3 supplementation increased the villus/crypt ratio (linear, quadratic; P < 0.05) and expression of zonula occludens protein 1 and nuclear factor-κ-gene binding in duodenum (P < 0.05). The supplementation of 25(OH)D3 reduced the abundance of Wittenberg polluted soil-2 bacteria, Synergistota, Bacteroidales, Colidextribacter, Eggerthellaceae, Oscillospira, Oscillibacter, UCG-009, Barnesiellaceae and Lachnospiraceae_UCG-010 in cecal contents (P < 0.05). Dietary requirements for 25(OH)D3 for ducks (60 to 76 wk), were estimated to be 3377 IU/kg for egg production, 3434 IU/kg for egg mass, and 3256 IU/kg for FCR. In summary, dietary 25(OH)D3 supplementation improved productive performance and influenced liver and plasma lipid homeostasis in aged laying ducks, which may be associated with the reduction of bacteria involved in carbohydrate metabolism in the cecum. Supplementing the basal diet with 3250 to 3450 IU/kg 25(OH)D3 is recommended for aged laying ducks (60 to 76 wk).

APOL1 polymorphisms are not influencing acute coronary syndrome risk in Czech males.

The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk

BackgroundCardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood. ObjectivesIn order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients. MethodsA case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls. ResultsPatients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate. ConclusionROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.

The plasma lipids with different fatty acid chains are associated with the risk of hemorrhagic stroke: a Mendelian randomization study.

Hemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke. The datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases. Two analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0_20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [p < 0.001; OR(95% CI) = 0.892(0.835-0.954)] and subarachnoid hemorrhage [p = 0.002; OR(95% CI) = 0.794(0.689-0.916)]. Conversely, lipids with linoleic acid chains (C18:2) were associated with an increased risk of intracerebral hemorrhage. This study identifies a potential causal relationship between lipids with different fatty acid side chains and the risk of intracerebral and subarachnoid hemorrhagic stroke, improving the understanding of the mechanisms behind the onset and progression of hemorrhagic stroke.

The role of pharmacological interventions in managing hyperlipidemia: A closer look at different drugs

Hyperlipidemia is a medical condition characterized by an increase in plasma lipids, including triglycerides, cholesterol, cholesterol esters, phospholipids, and plasma lipoproteins, which is a leading risk factor for cardiovascular diseases. The pathophysiology of hyperlipidemia is influenced by endothelial damage to blood vessels, leading to a loss of nitric oxide, increased inflammation, and lipid accumulation in the deepest layer of the endothelial wall. Lipid-lowering drugs like statins can reduce LDL levels by 25-60%, but they have negative impacts on clinical outcomes. Lipoprotein metabolism involves various enzymes, and atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques that reduce blood flow and oxygen supply, leading to heart damage and death. Lipoprotein metabolism involves various enzymes, including lipoprotein lipase (LPL), hepatic lipase (HL), lecithin cholesterol acyl transferase (LCAT), cholesterol ester transfer protein (CETP), microsomal triglyceride protein (MTP), and acyl Co-A transferase (ACAT). Atherosclerosis accumulates fat, cholesterol, and calcium in artery linings, creating fibrous plaques. This leads to reduced blood flow and oxygen supply, causing heart damage and death. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Reducing LDL and total cholesterol can significantly lower the incidence of strokes. Traditional antihyperlipidemic medicines have negative effects, and herbal treatments like onion, garlic, guggul, and Asparagus racemosus have been shown to have anti-diabetic and antihyperlipidemic properties.

Assessment of metabolic syndrome among hypertensive adult subjects in Enugu southeastern, Nigeria

Objective: Hypertension poses a significant burden on the general population, being responsible for increasing cardiovascular morbidity and mortality. The association of hypertension with dyslipidemia, enlarged waistline (obesity), and insulin resistance, also known as metabolic syndrome, further increases the overall cardiovascular risk of an individual. This study assessed the metabolic syndrome among adult hypertensive individuals in Enugu, Nigeria. Methods: One hundred and twenty participants(18-50 years) consisting of sixty hypertensive subjects, as test group and sixty normotensive subjects, as control group were recruited for this cross sectional study. Anthropometric parameters, waist circumference (WC), height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP) were measured and body mass index (BMI) calculated. Five milliliters of fasting blood samples were collected and used for the determination of fasting plasma glucose (FPG) and lipid profile (TC, TG, HDL-C, LDL-C, VLDL-C) using enzymatic colorimetric methods. Laboratory investigations were done in a hospital setting. Metabolic Syndrome (MetS) prevalence was estimated using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria. Data was analysed using the Statistical Package for the Social Sciences (SPSS) version 26. Results: The results showed a significant increase (P&lt; 0.05) in the mean ± SD of SBP (162.30 ± 18.94, 124.27 ± 8.85), DBP (106.77 ± 25.77, 83.40 ± 11.47), FPG (5.70 ± 1.90, 4.47 ± 0.64), TC (5.19 ± 0.913, 3.70 ± 0.94), LDL-C (3.05 ± 1.09, 1.68 ± 0.94) and a non-significant difference (P &gt; 0.05) in WC (91.48 ± 8.69, 91.96 ± 10.84), TG (1.35 ± 0.37, 1.26 ± 0.49), HDL-C (1.62 ± 0.45, 1.59 ± 0.50), VLDL-C (0.517 ± 0.16, 0.47 ± 0.64) of the hypertensive and normotensive subjects respectively. The prevalence of MetS in hypertensive subjects was 33.3%, while that of the control group (normotensives) was 3.3%. Conclusion: The study concludes that hypertension predisposes an individual to higher risk of developing MetS.

Assessing the genetic associations between plasma lipidomic profiles and psoriasis vulgaris.

Several studies have indicated a potential causal relationship between plasma standard lipids, such as high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and psoriasis. However, few studies have offered causal evidence of lipid species beyond these standard lipids. We conducted an analysis using a genome-wide association study (GWAS) dataset comprising 179 lipid species, including 13 types across four major categories, to identify instrumental variables (IVs) associated with plasma lipids. We utilized two GWAS datasets from the IEU and Finngen for psoriasis vulgaris as the outcome. A two-sample Mendelian randomization (MR) analysis was used to explore the causal relationship between 179 lipid species and psoriasis vulgaris in two datasets. Lipid species showing causal association in both psoriasis datasets were compared for overlap. Our study identified potential causal relationships between six lipid species and psoriasis vulgaris: phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylcholine (18:1_20:4), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1). In summary, elevated plasma levels of phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1) may increase the risk of psoriasis vulgaris. Conversely, plasma phosphatidylcholine (18:1_20:4) may play a protective role against psoriasis vulgaris.

Lipoprotein Lipidomics as a Frontier in Non-Alcoholic Fatty Liver Disease Biomarker Discovery.

Non-alcoholic fatty liver disease (NAFLD) is a progressive liver disease characterized by the build-up of fat in the liver of individuals in the absence of alcohol consumption. This condition has become a burden in modern societies aggravated by the lack of appropriate predictive biomarkers (other than liver biopsy). To better understand this disease and to find appropriate biomarkers, a new technology has emerged in the last two decades with the ability to explore the unmapped role of lipids in this disease: lipidomics. This technology, based on the combination of chromatography and mass spectrometry, has been extensively used to explore the lipid metabolism of NAFLD. In this review, we aim to summarize the knowledge gained through lipidomics assays exploring tissues, plasma, and lipoproteins from individuals with NAFLD. Our goal is to identify common features and active pathways that could facilitate the finding of a reliable biomarker from this field. The most frequent observation was a variable decrease (1-9%) in polyunsaturated fatty acids in phospholipids and non-esterified fatty acids in NAFLD patients, both in plasma and liver. Additionally, a reduction in phosphatidylcholines is a common feature in the liver. Due to the scarcity of studies, further research is needed to properly detect lipoprotein, plasma, and tissue lipid signatures of NAFLD etiologies, and NAFLD subtypes, and to define the relevance of this technology in disease management strategies in the push toward personalized medicine.

Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial.

Postbiotics could exert different metabolic activities in animal models of non-alcoholic fatty liver disease (NAFLD) and in humans affected by metabolic syndrome. This is a randomized, double-blind, placebo-controlled, parallel-group clinical trial that enrolled a sample of 50 Caucasian healthy individuals with NAFLD, defined as liver steatosis, and metabolic syndrome. After a 4-week run-in, the enrolled individuals were randomized to take a food for special medical purposes with functional release, one tablet a day, containing calcium butyrate (500 mg/tablet), zinc gluconate (zinc 5 mg/tablet), and vitamin D3 (500 IU/tablet), or an identical placebo for 3 months. Liver and metabolic parameters were measured at baseline and at the end of the study. No subject experienced any adverse events during the trial. In both groups, a significant decrease in total cholesterol (TC) and triglycerides (TG) plasma levels was observed at the randomization visit vs. pre-run-in visit (p < 0.05). Regarding liver parameters, after treatment, the fatty liver index (FLI) improved significantly vs. baseline values (p < 0.05) and vs. placebo group (p < 0.05) in the active treatment group, and the hepatic steatosis index (HSI) improved significantly vs. baseline values (p < 0.05). Moreover, after active treatment, TC, TG, and gamma-glutamyl transferase (gGT) improved significantly vs. baseline values (p < 0.05), and TC and TG improved vs. placebo group (p < 0.05), as well. In the placebo group, liver parameters remained unchanged after treatment; only TG improved significantly vs. baseline values (p < 0.05). In our study, we observed that the butyrate-based formula improved FLI and plasma lipid patterns in individuals affected by liver steatosis and metabolic syndrome.

Diverse carbon sources impact the biofloc system in brackish groundwater altering water quality, fish performance, immune status, antioxidants, plasma biochemistry, pathogenic bacterial load and organ histomorphology in Florida red tilapia

A 75-day rearing trial was completed to investigate the effectiveness of different biofloc systems (BFT) on the water quality, growth performance and health status of Florida red tilapia (FRT) grown in brackish groundwater (BGW). The trial consisted of the control and three types of BFT using different carbon sources (CS), starch (ST), rice bran (RB), and wheat bran (WB) in triplicate, expressed as BF-0, BF-ST, BF-RB, and BF-WB, respectively. Fish weighing 4.98 ± 0.01 g/fish were stocked in 250-L tanks at an initial stocking density of 25 fish. The findings demonstrated significant reductions in inorganic nitrogen by-product (NH3 and NO2) levels in all BFT groups compared to the control, with an increase in floc volume and floc nutritional value, in the BF-ST and BF-RB groups. Furthermore, fish in the BF-ST and BF-RB groups showed significant improvements in fish growth indices (final weight, weight gain, and FCR). Fish in the BFT groups showed significant improvement in kidney function indices and plasma lipids with no significant changes in liver enzyme activity compared to the control. Lower stress markers (glucose and cortisol) and higher digestive enzyme activity (lipase and protease), innate immune parameters and antioxidants were reported in fish of the BF-ST and BF-RB groups compared to the control fish. Histopathological inspection revealed that the BF-ST fish exhibited healthier livers and shared healthier intestines with BF-RB fish compared to the control group. In conclusion, RB is an appropriate CS with BGW for desert aquaculture due to its availability, inexpensiveness, and comparable outcomes with ST.

Automated preparation of plasma lipids, metabolites, and proteins for LC/MS-based analysis of a high-fat diet in mice

Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction platform that generates accurate, precise, and reproducible samples for metabolomic, lipidomic, and proteomic analyses from a single aliquot of plasma while minimizing hands-on time and avoiding contamination from plasticware. We applied mass spectrometry to examine the metabolome, lipidome, and proteome of 90 plasma samples to determine the effects of age, time of day, and a high-fat diet in mice. From 25 μl of mouse plasma, we identified 907 lipid species from 16 different lipid classes and subclasses, 233 polar metabolites, and 344 proteins. We found that the high-fat diet induced only mild changes in the polar metabolome, upregulated apolipoproteins, and induced substantial shifts in the lipidome, including a significant increase in arachidonic acid and a decrease in eicosapentaenoic acid content across all lipid classes.

Detection of pharmacolipidodynamic effects following the intravenous and oral administration of gefitinib to C57Bl/6JRj mice by rapid UHPLC-MS analysis of plasma

Omics-based biomarker technologies, including metabolic profiling (metabolomics/metabonomics) and lipidomics, are making a significant impact on disease understanding, drug development, and translational research. A wide range of patho-physiological processes involve lipids and monitoring changes in lipid abundance can give valuable insights into mechanisms of drug action, off target pharmacology and toxicity. Here we report changes, detected by untargeted LC–MS, in the plasma lipid profiles of male C57Bl/6JRj mice following the PO and IV administration of the epidermal growth factor receptor (EGFR) inhibitor gefitinib. Statistical analysis of the data obtained for both the IV and PO samples showed time-related changes in the amounts of lipids from several different classes. The largest effects were associated with a rapid onset of these changes following gefitinib administration followed by a gradual return by 24 h post dose to the type of lipid profile seen in predose samples. Investigation of the lipids responsible for the variance observed in the data showed that the PI, PC, LPC, PE and TG were subject to the largest disruption with both transient increases and decreases in relative amounts seen in response to administration of the drug. The pattern of the changes in the relative abundances of those lipids subject to variation appeared to be correlated to the pharmacokinetics of gefitinib (and its major metabolites). These observations support the concept of a distinct pharmacolipidodynamic relationship between drug exposure and plasma lipid abundance.

Effect of Replacing Sucrose in Beverages with Nonnutritive Sweetener Sucralose on Cardiometabolic Risk Factors Among Asian Indian Adults with Type2 Diabetes: A 12-Week Randomized Controlled Trial.

Country-specific evidence-based research is crucial for understanding the role of nonnutritive sweeteners (NNS) in managing type2 diabetes (T2D). The main aim of this study was to explore the effect of replacing sucrose with sucralose in coffee/tea in Asian Indians with type2 diabetes (T2D). This 12-week, parallel-arm randomized controlled trial included 210 participants with T2D, assigned to the intervention group, where sugar/sucrose in coffee or tea was substituted with sucralose, or the control group, where sugar/sucrose was continued. Lifestyle factors remained unchanged. The primary outcome was change in HbA1c. Secondary outcomes were changes in body weight (BW), body mass index (BMI), waist circumference (WC), lipid profiles, and inflammatory markers. At the end of 12weeks, no change was observed in HbA1c, fasting plasma glucose, lipid profile, and inflammatory markers between or within groups. There was a small but significant reduction in BW (- 0.5kg [95%CI - 1.0, - 0.1]; p = 0.02), BMI (- 0.2kg/m2 [- 0.4, 0.0]; p = 0.03), and WC (- 0.8cm [- 1.4, - 0.3]; p = 0.002) in the intervention group. Improvements were also observed in lipid accumulation product (p = 0.01), visceral adiposity index (p = 0.04), triglyceride/glucose index (p = 0.04), total energy intake (p = 0.04), and carbohydrate intake (p < 0.0001). In Asian Indians with T2D, replacing about 60kcal of added sucrose with sucralose in coffee/ tea had no benefit on glycemia but resulted in a small reduction in body weight, body mass index, and waist circumference. Clinical Trials Registry of India (CTRI/2021/04/032686).

Effect of Two Forms of Tenofovir on Duodenal Enterocytes - a Hypothesis for Different Effect of TDF and TAF on Body Weight and Plasma Lipids.

Tenofovir disoproxil fumarate (TDF) compared to tenofovir alafenamide (TAF) leads to lower body weight and plasma lipids by an unknown mechanism. We hypothesize that TDF, when absorbed, may damage enterocytes of the proximal duodenum, leading to reduced absorption of nutrients. People living with HIV, without significant gastrointestinal symptoms, receiving TDF (n=12) or TAF (n=12) containing regimen underwent esophagogastroduodenoscopies with duodenal biopsies. Plasma/serum concentrations of nutrients absorbed from proximal duodenum and serum intestinal fatty-acid-binding protein (I-FABP), a marker of enterocyte damage, were measured. COX/SDH histochemical staining and electron microscopy (EM) were conducted to evaluate mitochondria. Five patients in TDF (celiac disease (excluded from further analyses), helicobacter gastritis, and three esophagitis) and two in TAF group (two esophagitis) had a pathological finding in esophagogastroduodenoscopy. Villi were flatter (337 (59) vs. 397 (42) μm, p=0.016), crypts non-significantly deeper (200 (46) vs. 176 (27) μm, p=0.2), and villus to crypt ratio lower (1.5 (0.42) vs. 2.5 (0.51), p=0.009) in TDF vs. TAF group. I-FABP concentration was higher in TDF vs. TAF group (3.0 (1.07) vs. 1.8 (0.53) ng/ml, p=0.003). TDF group had numerically but not statistically significantly lower concentrations of folate, vitamins A, B1, D, and E. COX/SDH staining showed signs of mitochondrial damage in 10 participants in TDF and 11 in TAF group. EM studies showed similar mitochondrial damage in both groups. Duodenal villous alterations may explain TDF-associated decrease in body weight and plasma lipids. Larger studies are needed to evaluate concentrations of nutrients absorbed from duodenum among TDF users.