Plasma Triglyceride Levels Research Articles

Inhibition of the ANGPTL3/8 Complex for the Prevention and Treatment of Atherosclerotic Cardiovascular Disease.

Dyslipidemia is a casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with dyslipidemias. Angiopoietin-like protein 3 (ANGPTL3) and ANGPTL8 play key roles in triglyceride trafficking and energy balance in humans. We review the functional role of these ANGPTL proteins in the regulation of lipoprotein metabolism, and recent clinical trials targeting ANGPTL3 and ANGPTL3/8 with monoclonal antibody and/or nucleic acid therapies, including antisense oligonucleotides and small interfering RNA. Cumulative evidence supports the roles of ANGPTL3 and ANGPTL8 in lipid metabolism through inhibition of lipoprotein lipase and endothelial lipase activity. ANGPTL3 and ANGPTL3/8 inhibitors are effective in lowering plasma triglycerides and low-density lipoprotein (LDL)-cholesterol, with the possible advantage of raising high-density lipoprotein (HDL)-cholesterol with the inhibition of ANGPTL3/8. Therapeutic inhibition of ANGPTL3 and ANGPTL3/8 can lower plasma triglyceride and LDL-cholesterol levels possibly by lowering production and upregulating catabolism of triglyceride-rich lipoprotein and LDL particles. However, the effect of these novel agents on HDL metabolism remains unclear. The cardiovascular benefits of ANGPTL3 and ABGPTL3/8 inhibitors may also include improvement in vascular inflammation, but this requires further investigation.

Age of Cafeteria Diet Onset Influences Obesity Phenotype in Mice in a Sex-Specific Manner.

We investigated the influence of sex and the age of obesogenic diet initiation on the obesity phenotypes at a later age. C57Bl mice started the Cafeteria Diet (CafD, with increased fat and carbohydrates, ad libitum, from 7 weeks of age (7CafD, pre-puberty) or 17 weeks of age (7CafD, post-puberty) while control C57Bl mice were fed regular chow. At 27 weeks of age, 7CafD males (n = 9) compared to 17CafD males (n = 7) had lower body weight, white adipose tissue (WAT) relative weight, and plasma cholesterol levels, and a higher expression of thermogenic genes in WAT and brown adipose tissue (BAT), and fatty acid oxidation (FAO) and insulin signalling genes in muscles. The 7CafD females (n = 8), compared to 17CafD females (n = 6), had higher plasma triglyceride levels and hepatic glycogen content, but lower insulin sensitivity and hepatic expression of FAO and insulin signalling genes. The 7CafD females, compared to 7CafD males, had more WAT, and a reduced expression of FAO genes in muscles and thermogenic genes in WAT. The 17CafD females, compared to 17CafD males, had lower plasma leptin and insulin levels, and higher insulin sensitivity and expression of insulin signalling genes in the liver and muscles. Thus, the initiation of the obesogenic diet before puberty led to a more adaptive metabolic phenotypes in males, and after puberty, in females.

Positive Changes in Body Composition and Profiles of Individuals with Diabetes 3 Years Following Laparoscopic Sleeve Gastrectomy in Japanese Patients with Obesity.

We analyzed the changes in obesity, glucose metabolism, and body composition over a 3-year period in Japanese patients with obesity following laparoscopic sleeve gastrectomy (LSG). Body weight, parameters related to diabetes such as glycated hemoglobin (HbA1c), and electrical impedance analysis were used to assess body composition in forty-eight Japanese patients with obesity before surgery and 6 months, 1 year, 2 years, and 3 years after LSG. At 6 months, 1, 2, and 3 years post-LSG, there were significant reductions in body weight, body mass index, blood pressure, fasting plasma glucose, triglyceride, and HbA1c levels. Six months after LSG, fat mass (FM), muscle mass (MM), and %FM all showed a decrease compared to pre-treatment values (all p < 0.05). FM and %FM remained in a decreased state until 3 years had passed. In contrast, %MM increased at 6 months post-LSG and was maintained up to 3 years post-LSG (all p < 0.05). Furthermore, changes in FM and %FM were associated with changes in body weight and A1C. In contrast, change in %MM exhibited a negative correlation with body weight and A1C following LSG. Finally, multivariate regression analyses demonstrated that alterations in FM were independent factors affecting body weight in patients with obesity 3 years after LSG. We observed improvements in FM, fasting plasma glucose, and HbA1c levels over a 3-year period in Japanese patients after LSG. The reduction in FM and maintenance of %MM after LSG were suggested as possible links between the effects of LSG on obesity and diabetes over 3 years.

Effect of Butaphosphan and Cyanocobalamin on the Metabolic Profile, Oxidative Stress and Prophylaxis of Ovine Pregnancy Toxemia.

The study was conducted to evaluate the effect of butaphosphan and cyanocobalamin (BC) on the metabolic profile, oxidative stress in Kashmiri merino ewes and its effect on the prophylaxis of Ovine pregnancy toxemia (PT). A total of 48 ewes were randomly divided into three groups, each consisting of 16 ewes. High dose BC (HBC): Ewes were given 0.2 mL BC/kg body weight, subcutaneously (SC) weekly from 6 weeks pre-lambing to lambing. Low dose BC (LBC): Ewes were given 0.1 mL BC/kg body weight, SC weekly from 6 weeks pre-lambing to lambing. No BC (CON): Ewes were given 0.2 mL normal saline/kg body weight, SC. Weekly from six pre-lambing to lambing. A significant effect of treatment was observed on non-esterified fatty acid (NEFA; p = 0.06), beta hydroxybutyric acid (β-HBA, p = 0.008), fructosamine (p = 0.034) and oxidative stress indices (OSI; p = 0.026) with less NEFA, β-HBA, OSI and more fructosamine levels in HBC followed by LBC. The BC did not affect glucose, cholesterol, blood urea nitrogen, creatinine, total antioxidant capacity, calcium and phosphorus however a significant difference was observed along the sampling time in all the three groups. Plasma triglyceride, aspartate aminotransferase and total oxidant status levels showed a significant treatment-time interaction. Taking 0.8 mmol/L β-HBA as the cutoff limit for subclinical PT, only HBC was able to significantly control PT at 3 weeks pre-lambing (OR; 5.57; p = 0.035), at 2 weeks pre-lambing (OR: 9.53; p = 0.007), at 1-week pre-lambing (OR: 6.60; p = 0.017) and at lambing (OR: 5.57; p = 0.035). In conclusion, there was a positive effect of BC treatment on the energy metabolism in pregnant ewes and it helped in the amelioration of oxidative stress and hence can be used in the prophylaxis of PT.

Anatomical and carcass traits, partition of fat deposits, and meat quality in culled adult goats finished with high-fat diet

The objective of this study was to examine the impact of a high-fat finishing diet on the in vivo performance, anatomical and carcass characteristics, and meat quality of adult culled goats. Over a period of 28 days leading up to slaughter, eighteen adult culled goats were subjected to a finishing diet provided in quantities sufficient to meet 3.0 times the nutritional requirements of adult non-dairy maintenance goats. The female goats were divided into two groups: one fed with the baseline diet without fat supplementation (n = 9) and the other fed a diet concentrated supplemented with whole full-fat linseed (n = 9). The diets varied in fat content (2.8% vs. 8.4% DM). The high-fat group exhibited a higher dry matter intake compared to the control group (+37%), along with elevated plasma cholesterol and triglyceride levels. The control group experienced a significant decrease in daily weight gain between the second and final week of the finishing period (-70%), in contrast to the increase observed in the high-fat group (+59%). At slaughter, no differences were noted between the groups in anatomical and carcass characteristics. Additionally, no differences were found between the diets regarding proximate composition, pH, yellow color component, and lightness of loin. The high-fat group exhibited a higher redness of loin. The inclusion of high-fat levels in finishing diets for culled adult goats allows for increased feed intake and performance but does not appear to affect carcass or meat quality.

Case detection of familial hypercholesterolemia using various criteria during an annual health examination in the workplace

BackgroundEarly diagnosis and appropriate treatment of subjects with familial hypercholesterolemia (FH) could prevent cardiovascular disease (CAD). ObjectiveWe aimed to identify potential cases of FH during a workplace screening and to explore their clinical data. MethodPersonnel who attended an annual health examination were invited to answer a questionnaire and to provide consent to review their laboratory results. FH was clinically diagnosed using any one of the three standard criteria: Dutch Lipid Clinic Network (DLCN), Simon Broome (SB), and Make Early Diagnosis to Prevent Early Deaths (MEDPED). Clinical characteristics were compared between FH and unlikely FH subjects. ResultsAmong 6607 participants, potential cases of FH were identified in 2.5 % by DLCN, 4.0 % by SB, and 0.8 % by MEDPED alone. Premature CAD, hypertension, and current smoking were significantly more common in potential FH subjects than in unlikely FH subjects. Potential FH subjects also had significantly higher body mass index, waist circumference, blood pressure, fasting plasma glucose and triglyceride levels than unlikely FH subjects. Among potential FH subjects, lipid-lowering medication was used in 28.4 %. The achievement of the LDL-C goal (<100 mg/dL) in potential FH subjects was significantly lower than that in unlikely FH subjects (15 % vs. 28 %, respectively, P = 0.005) despite a higher rate of high-intensity statin use (25 % vs. 10 %, respectively, P = 0.002). ConclusionThe workplace screening of FH detected a significant number of potential FH subjects with higher cardiovascular risk. This strategy identified individuals for whom intensification of both lifestyle modifications and pharmacological treatment should be a priority.

Effect of Lifestyle Modification on Plasma Lipids of Adults in a Part of North Central Nigeria

Background: Plasma lipids are precursors of adrenal and gonadal steroid hormones, bile acids as well as important component of animal cell wall. However, abnormal plasma lipids are major risk factor for cardiovascular diseases globally. Researchers are currently considering lifestyle modification such as exercise, as an approach to maintaining normal plasma lipids level as well as addressing abnormal ones. Methodology: This study investigated the effect of lifestyle modification (vigorous intensity aerobic exercise regimen) on plasma triglycerides and low density lipoprotein-cholesterol of adults in Benue State University, Makurdi. The design of the study was guided by two research questions. Two hypotheses were formulated and tested at 0.05 level of significance. The study adopted two group pretest posttest quasi experimental design. The study population comprises twenty-one (21) Benue State University staff in the experimental group, and another twenty-one (21) for the control group. The proforma used for the data collection was validated by three experts, one from measurement and evaluation, one from the Department of Human Kinetics and Health Education and one from College of Health Sciences; all in Benue State University, Makurdi. Data generated were analyzed using Statistical Package for Social Sciences (SPSS Version 25). A descriptive statistics, mean and standard deviation were used to answer the research questions, and inferential statistics, Analysis of Covariance (ANCOVA) and Paired Samples Test were used to test the hypotheses at 0.05 level of significance. Results: The findings revealed that out of the 21 participants in the two groups, 12(57.14%) were males, while 9(42.86%) were females. The age range in the control group was between 28 to 65years, while that of the experimental group was between 36-68years. Vigorous intensity aerobic exercise regimen was found to have statistically significant effect on plasma low density lipoprotein-cholesterol (P = 0.000&lt;0.05). Even though plasma triglyceride was found to be reduced by vigorous intensity aerobic exercise regimen, the level of the reduction was found not to be statistically significant (P = 0.293 &gt; 0.05). Conclusion: The study concluded that healthcare workers should henceforth incorporate vigorous intensity aerobic exercise regimen prescription in public health awareness on the maintenance of plasma level of triglycerides and low density lipoprotein-cholesterol, as well as clinical management of patients with abnormal plasma low density lipoprotein-cholesterol.

Combination therapy with GalNAc-siRNA drugs targeting both PCSK9 and APOC3 resulted in enhanced lipid lowering in mice

Abstract Introduction Aggressive lowering of both atherogenic low-density lipoprotein cholesterol (LDL-C) and triglyceride-rich lipoproteins (TRLs) could reduce residual atherosclerotic cardiovascular disease (ASCVD) risk. Drugs targeting PCSK9 or APOC3 have shown good lipid-lowering effects in clinic. Here, we have developed GalNAc-conjugated siRNAs, RBD7022 targeting PCSK9 and RBD5044 targeting APOC3, as novel therapeutic agents to lower LDL-C and triglyceride (TG) plasma levels respectively. Each drug shows potent and durable effect in silencing its own target. However, it is unknown whether the combined therapy with siRNA drugs targeting both PCSK9 and APOC3 will generate enhanced effects in lipid lowering. Purpose To investigate the effects of fixed-dose combination of RBD7022 and RBD5044 on LDL-C, TG and total cholesterol (TC). Methods RBD7022 and RBD5044 completely match the human PCSK9 and APOC3 transcripts respectively. RBD7022 has 2 nucleotide mismatches with mouse pcsk9, but still shows silencing activity in mice, while RBD5044 has no activity due to 5 mismatches with mouse apoc3. Therefore, humanized APOC3 transgenic mice were used in this study, which had serious hypertriglyceridemia with relatively high cholesterol and TG levels. They were randomized into 8 groups with treatment of RBD7022 (1 mg/kg or 3 mg/kg), RBD5044 (3 mg/kg or 6 mg/kg), or 3 different dose combinations of RBD7022 and RBD5044, as well as PBS control. All animals were administrated once on Day 1. Plasma was collected to quantify lipid biomarkers. Results RBD7022 showed a robust effect on LDL-C reduction, with inhibition rates of 45% in 3 mg/kg and 43% in 6 mg/kg, indicating 3 mg/kg was a saturated dose for RBD7022 in LDL-C lowering. RBD5044 showed a dose-dependent effect on LDL-C reduction, with inhibition rate of 52% at 1 mg/kg and 59% at 3 mg/kg. Interestingly, significantly enhanced LDL-C reduction was observed in the combination groups, with 67% reduction in LDL-C at RBD5044 1 mg/kg plus RBD7022 3 mg/kg, 73% reduction in LDL-C at RBD5044 3 mg/kg plus RBD7022 3 mg/kg and 78% reduction in LDL-C at RBD5044 3 mg/kg plus RBD7022 6 mg/kg, showing dose-dependent effects (Figure 1A). Enhanced TC reduction was also found in combination at RBD5044 3 mg/kg plus RBD7022 6 mg/kg compared with RBD5044 or RBD7022 alone. RBD5044 showed a dose dependent effect on TG reduction with inhibition rates of 56% at 1 mg/kg and 83% at 3 mg/kg. RBD7022 treatment alone did not show significant effect on TG reduction. No added effects of RBD7022 on TG levels was found in the combination with RBD5044, indicating the TG lowering was induced by RBD5044. Conclusions The combination of RBD7022 targeting PCSK9 and RBD5044 targeting APOC3 simultaneously reduce LDL-C and TC levels. The combination of RBD7022 and RBD5044 could be a better therapeutic option to further reduce LDL-C, particularly for mixed hyperlipidemia patients and other high-risk individuals with both high LDL-C and high TG levels.Figure 1

Use of Lupinus albus as a Local Protein Source in the Production of High-Quality Iberian Pig Products.

The replacement of soybean meal with sweet white lupin (Lupinus albus L.) seeds was investigated in the diets of Iberian pigs during the growing and fattening phases, evaluating its effects on growth performance, carcass traits, and meat quality. Iberian pigs (n = 50) were divided into two dietary groups (n = 25 per group), receiving either a lupin-based concentrate or a soybean meal-based concentrate. The data were analysed using one-way analysis of variance (ANOVA), with a significance level of p < 0.05. The results showed that lupin substitution had no adverse effect on body weight, average daily gain, or carcass characteristics. No significant differences were observed in meat quality parameters such as pH, colour, and texture. However, significantly (p = 0.007) lower levels of saturated fatty acids (SFA) content were found in the intramuscular fat of pre-finishing (primor) pigs fed lupin-based diets. In addition, these pigs had lower plasma triglyceride levels at the end of the growing phase. Overall, the results suggest that sweet white lupin is a viable alternative protein source in Iberian pig production, offering potential health benefits in line with consumer preferences for sustainably produced, healthier meat products, without compromising production efficiency or product quality.

A diet high in glucose and deficient in dietary fibre causes fat accumulation in the liver without weight gain

This study investigated whether a standard calorie diet that is high in glucose and deficient in dietary fibre (described as HGD [high glucose diet]) induces hepatic fat accumulation in mice. We evaluated hepatic steatosis at 7 days and 14 days after the commencement of the HGD. Hepatic triglycerides and areas of oil droplets increased in the HGD group both at day 7 and day 14, whereas weight gain, weight of epididymal fat, and plasma levels of triglycerides were unaffected by HGD consumption. A microarray analysis of the livers revealed that the expression of lipogenesis-related genes was the most affected by HGD consumption. Furthermore, HGD consumption induced the expression of hepatic proteins of fatty acid synthetase, acetyl-CoA carboxylase alpha, and stearoyl-CoA desaturase 1, which are known to be involved in the synthesis of triglyceride. These results indicate that HGD consumption causes fat accumulation in the liver, with an increase in enzymes that are involved in de novo lipogenesis without an accompanying weight or obesity phenotype. Our new findings suggest that HGD consumption could serve as a breeding ground for liver steatosis.

Saccharomyces boulardii Mitigates Fructose-Induced Non-Alcoholic Fatty Liver in Rats.

Background and Objectives: Non-alcoholic fatty liver disease (NAFLD) is a growing global health concern closely linked to metabolic disorders, including obesity, insulin resistance, and dyslipidemia. Emerging evidence suggests that the gut-liver axis plays a critical role in the pathogenesis of NAFLD, with recent research highlighting the influence of gut microbiota, including fungal species such as Saccharomyces boulardii (S. boulardii). This study aimed to evaluate the effects of S. boulardii on lipid metabolism and oxidative stress in a rat model of fructose-induced NAFLD. Materials and Methods: Thirty Wistar rats were divided into three groups: a control group, a fatty liver group induced by 35% fructose supplementation, and a treatment group receiving S. boulardii (100 mg/kg/day) after fructose induction. Results: Biochemical analyses revealed that the treatment group exhibited significantly lower plasma levels of malondialdehyde (MDA), alanine aminotransferase (ALT), total triglycerides, and cholesterol compared to the untreated fatty liver group (p < 0.05). Furthermore, liver tissue analysis showed a marked reduction in lipid accumulation and fatty infiltration in the treatment group, with no visible lipid vacuoles in hepatocytes. The expression of aquaporin-8 (AQP8) and sirtuin-1 (SIRT1), key markers associated with hepatocyte function and lipid metabolism, was significantly higher in the S. boulardii group compared to the fatty liver group (p < 0.001). Conclusions: These findings indicate that S. boulardii supplementation mitigates the metabolic and oxidative stress-related alterations associated with fructose-induced NAFLD. In conclusion, our study suggests that S. boulardii exerts protective effects on the liver by reducing lipid accumulation and oxidative stress, highlighting its potential as a therapeutic intervention for NAFLD.

FITM2 deficiency results in ER lipid accumulation, ER stress, and reduced apolipoprotein B lipidation and VLDL triglyceride secretion in vitro and in mouse liver

ObjectivesTriglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL. We hypothesized that in the liver, in addition to promoting cytosolic LD formation, FITM2 would also transfer TG from its site of synthesis in the ER membrane to nascent VLDL particles within the ER lumen. MethodsExperiments were conducted using a rat hepatic cell line (McArdle-RH7777, or McA cells), an established model of mammalian lipoprotein metabolism, and mice. FITM2 expression was reduced using siRNA in cells and by liver specific cre-recombinase mediated deletion of the Fitm2 gene in mice. Effects of FITM2 deficiency on VLDL assembly and secretion in vitro and in vivo were measured by multiple methods, including density gradient ultracentrifugation, chromatography, mass spectrometry, stimulated Raman scattering (SRS) microscopy, sub-cellular fractionation, immunoprecipitation, immunofluorescence, and electron microscopy. Main findings1) FITM2-deficient hepatic cells in vitro and in vivo secrete TG-depleted VLDL particles, but the number of particles is unchanged compared to controls; 2) FITM2 deficiency in mice on a high fat diet (HFD) results in decreased plasma TG levels. The number of apoB100-containing lipoproteins remains similar, but shift from VLDL to low density lipoprotein (LDL) density; 3) Both in vitro and in vivo, when TG synthesis is stimulated and FITM2 is deficient, TG accumulates in the ER, and despite its availability this pool is unable to fully lipidate apoB100 particles; 4) FITM2 deficiency disrupts ER morphology and results in ER stress. Principal conclusionsThe results suggest that FITM2 contributes to VLDL lipidation, especially when newly synthesized hepatic TG is in abundance. In addition to its fundamental importance in VLDL assembly, the results also suggest that under dysmetabolic conditions, FITM2 may be an important factor in the partitioning of TG between cytosolic LDs and VLDL particles.

Molecular mechanism of ectopic lipid accumulation induced by methylglyoxal via activation of the NRF2/PI3K/AKT pathway implicates renal lipotoxicity caused by diabetes mellitus.

Patients with chronic kidney disease (CKD) have a high incidence of dyslipidemia comprising high triglyceride (TG) and low high-density lipoprotein (HDL)-cholesterol levels. An abnormal increase of TGs within cells can lead to intracellular lipid accumulation. In addition to dyslipidemia, hyperglycemia in diabetes may elicit ectopic lipid deposition in non-adipose tissues. Hyperglycemia increases intracellular levels of methylglyoxal (MG) leading to cellular dysfunction. A deficit of glyoxalase I (GLO1) contributes to dicarbonyl stress. Whether dicarbonyl stress induced by MG causes renal lipotoxicity through alteration of lipid metabolism signaling is still unknown. In this study, mice with high fat diet-induced diabetes were used to investigate the renal pathology induced by MG. NRK52E cells treated with MG were further used in vitro to delineate the involvement of lipogenic signaling. After treatment with MG for 12 weeks, plasma TG levels, renal fatty changes, and tubular injuries were aggravated in diabetic mice. In NRK52E cells, MG activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and sterol regulatory element-binding protein 1 (SREBP1), resulting in stimulation of fatty acid synthase. The intracellular accumulation of lipid droplets was mainly contributed by TGs, which increased the oxidative stress accompanied by high Nrf2 expression. In addition, MG time-dependently activated cyclin D, cyclin-dependent kinase 4 (CDK4), and cleaved caspase-3, evidencing that G0/G1 arrest was associated with apoptosis of NRK52E cells. In conclusion, our studies revealed the mechanism of lipotoxicity caused by MG. The target of such dicarbonyl stress may become a promising therapy for diabetic CKD.

Berberine and Berberine Nanoparticles Mitigate Scopolamine-Induced Amnesia in Rats

Abstract Introduction/Objective Berberine (BER) has garnered attention in research for its multifaceted biochemical and pharmacological properties, positioning it as a promising natural remedy. Conversely, scopolamine (SCO) functions as a non-selective muscarinic receptor antagonist, disrupting central cholinergic neurotransmission and impairing learning and short-term memory. Methods/Case Report Forty-two male Wistar rats were procured from the National Research Center in Cairo, Egypt, and allocated randomly into seven groups, each comprising six rats. The groups were as follows: Sham Control (no treatment), BSA Control (received oral administration of 1 ml Bovine Serum Albumin-NP solution daily for 28 days), BRB-NP Control (received oral administration of BRB-NP nanoparticles at 5 mg/kg/day for 28 days), Induced Group (intraperitoneal injection of SCO at 2 mg/kg dissolved in saline once daily for 28 days), BER Treated Group (received BER at 50 mg/kg suspended in saline followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), BSA Treated Group (received oral administration of 1 ml BSA-NP solution followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days), and BER-NP Treated Group (received oral administration of BER-NP at 5 mg/kg followed by intraperitoneal injection of SCO at 2 mg/kg after 40 minutes daily for 28 days). Whole blood was collected via heart puncture, and brain tissue was promptly extracted for brain homogenate preparation. Routine biochemical assays were conducted on serum and brain samples. Results (if a Case Study enter NA) Statistically significant differences were observed among the seven experimental rat groups concerning plasma AST, albumin, total protein, and triglyceride levels, while differences in ALT and total cholesterol were non-significant. Regarding brain parameters, significant differences were noted among groups in total protein, cholesterol, phospholipids, and uric acid levels. Conclusion Treatment with BRB NPs or free berberine led to a progressive increase in brain protein levels and a decrease in cholesterol content (p&amp;lt;0.05). Additionally, SCO administration resulted in a gradual reduction in brain phospholipid content, while treatment with BER NPs, regardless of the rat’s condition, exhibited the highest phospholipid levels (p&amp;lt;0.05). Furthermore, administration of BSA or free BRB improved brain uric acid levels (p&amp;lt;0.05).

Genetic Susceptibility to Hidradenitis Suppurativa and Predisposition to Cardiometabolic Disease.

Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear. To investigate the genetic correlation between HS and cardiometabolic disease. This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses. The PRS for HS. Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status. The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index. These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

Potential causal and temporal relationship between plasma triglyceride levels and circulating leukocyte

Circulating triglyceride (TG) and leukocytes, the main components of the vascular system, may impact each other and co-fuel atherosclerosis. While the causal relationship between plasma TG levels and leukocyte counts remains unclear. Bidirectional Mendelian randomization (MR) analysis was conducted to investigate the potential causal relationship between TG levels and the counts of leukocytes and their subtypes. A cross-lagged panel model (CLPM) using longitudinal healthy screening data (13,389 adults with a follow-up of 4 years) was fitted to examine the temporal relationship between them. Genetically predicted plasma TG levels were positively associated with total leukocyte counts (TLC) [β(se) = 0.195(0.01)], lymphocyte counts (LC) [β(se) = 0.196(0.019)], and neutrophil counts (NC) [β(se) = 0.086(0.01)], which remained significant after adjusting for several confounders. Inversely, the genetically predicted TLC [β(se) = 0.033(0.008)], LC [β(se) = 0.053(0.008)], and NC [β(se) = 0.034(0.008)] were positively associated with plasma TG levels. However, when all three of them were put into the MR model adjusted for each other, only LC was significantly associated with TG levels. There was no association between genetically predicted TG levels and monocyte counts (MC), basophil counts, and eosinophil counts. The results of CLPM showed that the temporal effect of elevated TLC, MC, LC, and NC on plasma TG levels was stronger than the inverse effect. Our findings suggest causal associations of plasma TG levels with TLC, LC, and NC. In turn, LC was positively associated with plasma TG levels. Additionally, elevated circulating LC may precede high plasma TG levels.

High fat intake aggravates hyperlipidemia and suppresses fatty liver symptoms induced by a high-sucrose diet in rats.

Overconsumption of sucrose or fat is widely acknowledged as a prominent feature of unhealthy dietary patterns. Both factors commonly co-occur and are recognized as hallmarks of the Western diet, which is an important contributor to non-communicative diseases. In this study, we investigated the hazards of high sucrose or fat intake, either alone or in combination. Wistar rats were divided into four groups and fed a control starch diet, high-sucrose diet, high-fat diet, or high-sucrose/fat diet for 30 days. High fat intake increased body weight and visceral and subcutaneous adipose tissue weights. Both high-sucrose and -fat diets were associated with increased plasma triglyceride and glucose levels, and high sucrose also elevated plasma cholesterol levels. The combination of high sucrose and fat synergistically elevated plasma triglyceride levels. The high-sucrose diet increased liver weight and hepatic total lipid and triglyceride levels, whereas this increase was suppressed by the high-fat diet. The high sucrose increased the mRNA levels of hepatic genes involved in fatty acid synthesis and transport (ACLY, ACACA, FAS, ELOVL6, SCD1, SREBP1, and CD36), whereas the high fat suppressed the high sucrose-induced expression of these genes. We observed that high sucrose and fat contents differently exerted their effects on hyperlipidemia and fatty liver. Furthermore, high fat aggravated hyperlipidemia and suppressed fatty liver induced by high sucrose.

Effect of chia seeds or concentrated fish oil on cardiometabolic risk markers in subjects with hypertriglyceridaemia: a parallel clinical trial.

The beneficial effects of n-3 polyunsaturated fatty acids (PUFA) in reducing high blood triglyceride (TG) levels have been well demonstrated. This study aimed to investigate the effect of chia seeds on blood TG and its associated cardiometabolic factors in hypertriglyceridaemic individuals. This three-group randomised controlled trial compared the effects of a low-calorie diet (n = 22), a low-calorie diet with chia seeds (30 g/day, n = 22) or a low-calorie diet with concentrated fish oil (1.8 g/day of n-3 long-chain PUFAs, n = 22) in patients with hypertriglyceridaemia. Anthropometrics, fasting blood lipids, proprotein convertase subtilisin/kexin type 9, insulin, adiponectin, leptin and interleukin-6 levels were measured. After 8 weeks, the mean reduction in weight exhibited by the three groups was not statistically different (2.0, 2.7 and 2.8 kg, respectively, for the control, fish oil and chia seed groups). The plasma TG decreased in both the chia seed and fish oil groups in comparison to the control group (p = 0.001). However, no significant difference was observed between the chia seed and fish oil groups (change from baseline mean: 145.2 and 136.7 mg/dL for the chia seed and fish oil groups, respectively). The consumption of chia seeds was associated with a reduction in diastolic blood pressure (change from baseline mean: 8.4 mmHg) compared to the other two groups. No significant alterations were observed in the other blood biochemical factors between the three groups. In people with moderate hypertriglyceridaemia, a low-calorie diet with 30 g of chia seeds compared to fish oil supplements containing 1.8 g of long-chain PUFAs has a similar effect on reducing plasma TG levels, whereas it has a higher blood pressure-lowering effect.

Effects of oxygen levels and temperature on growth and physiology of pikeperch juveniles cultured in a recirculating aquaculture system

This study aimed to understand how environmental factors, specifically water temperature and oxygen saturation, affect the growth performance and physiology of pikeperch (Sander lucioperca) juveniles in recirculating aquaculture systems (RASs). Given the importance of optimising growth conditions in aquaculture to maximise efficiency, it aims to assess whether different combinations of oxygen levels and temperatures can enhance growth while maintaining the physiological health and welfare of the fish. The experimental design included the culturing pikeperch juveniles (22.7 ± 7.1 g) were exposed to hypoxia (78 ± 14%), normoxia (105 ± 12%), and hyperoxia (140 ± 18%) conditions for 72 days. This was conducted at two temperatures, 20 °C and 23 °C, each in a separate but identical RAS. The level of oxygen supply was controlled with micro bubble diffusers on the bottom of each tank. The hyperoxia at 23 °C positively affected total length, BW, specific growth rate, feed intake and feed conservation rate (FCR). The slowest growth and feed intake, along with the highest FCR, were observed in hypoxia at 20 °C. Fish reared under 23 °C exhibited significantly higher visceral-somatic index (3.54 ± 0.83 at 23 °C and 2.76 ± 0.73 at 20 °C) regardless of oxygen levels. It was primarily responsible for the observed growth difference (Final BW: 58.3 ± 18.8 g at 23 °C and 53.0 ± 18.3 g at 20 °C). The water temperature also affected haematocrit, haemoglobin, leucocyte count, mean corpuscular haemoglobin, mean corpuscular volume (MCV) of the blood cells; the concentration of lymphocytes, neutrophile granulocyte bands and segments. Among biochemical markers, temperature affected cytoplasmic and mitochondrial enzymes, ammonia and triglyceride levels in blood plasma. Elevated antioxidant activity was observed in muscle, intestine and liver tissues. Oxygen levels demonstrated significant effects on growth, feed intake and conversion, the MCV of the blood cells, the concentration of the glucose, lactate and ammonia in blood plasma, and antioxidant biomarkers in the liver tissue. The analysis indicated a significant effect of oxygen on energy metabolism. The results showed hyperoxia under 23 °C create conditions for the highest growth and feed intake, high feed utilisation. There are, however, concerns about the physiological conditions and welfare of intensively cultured pikeperch juveniles, as higher feed intake led to increased visceral fat content in the body, elevated antioxidant activity in the liver, muscle and intestine tissues, morphology of blood cell, and energy metabolism.

Ceramide As A Potential Tumor Marker For Diagnosis Of Prostate Cancer And Its Association With Lipid Profile

Background: Prostate cancer (PCa) is the second most frequent type of malignancy cancer among men worldwide. Ceramides are fatty acid derivatives of sphingoid bases, and formed not only through the de novo biosynthetic pathway, but also from the degradation of glycosphingolipids (GSLs) and ceramide-1-phosphate. Dyslipidaemia is part of metabolic syndrome, characterized by an alteration of the plasma lipid profile, including Cholesterol, HDL, and triglyceride levels. Objective Evaluate serum ceramide as tumer marker of prostate cancer and its association with lipid profile. Method This case- control study was carried out at Department of Biochemistry, College of Medicine, University of Baghdad and at Urology department, Ghazi Al-Hariri Hospital for surgical speciality during the period from March 2022 to May 2023. It included 120 men patients, 60 men patients who newly diagnosed to have primary prostate cancer (PCa), and 60 men were apparently healthy men. Investigations included serum measurements of ceramide by using enzyme linked immunosorbent assay(ELISA) and also measurement of lipid profile by using semi-auto biochemistry analyzer.Results The results of the present study showed that there was a significant differences in ceramide in prostate cancer patients as compared with the control group The results also showed that the S.Cholesterol, and S.Triglyceride were higher in the patients group compared to the controls group with significant statistical difference. Conclusion. According to the results obtained we can suggest that higher levels of ceramide, Cholesterol and Triglyceride may be associated with risk of prostate cancer.