Lower Triglyceride Levels Research Articles

Особенности морфофункционального и физиологического состояния осетровых рыб с нефрокальцинозом в условиях садковой аквакультуры

When growing sturgeon fish in cages, which are especially valuable nowadays, great attention should be paid to their health. Along with other pathological manifestations of various natures, a disease such as kidney nephrocalcinosis can pose a potential danger to these aquaculture objects. This pathology was recorded in juvenile sterlet (age – 0+ years), in immature individuals of Russian sturgeon (age – 2 years), in which clinical and pathological examinations were carried out, including pieces of kidneys were selected for histological analysis, blood samples for carrying out hematological and biochemical studies. The appearance of nephrocalcinates in the kidneys of sturgeon fish was confirmed using histological methods: corresponding pathological transformations were found on micropreparations of the kidneys of Russian sturgeon and sterlet. Morphophysiological changes in the condition of the kidneys of the studied sturgeon fish can be assessed as moderate and minor, not life-threatening. Thus, 60% of the examined individuals of Russian sturgeon did not have any detected pathohistological changes in the organ; among sterlet there were 80% of such individuals. When analyzing hematological and biochemical blood parameters, deviations of some indicators were found. Thus, the sterlet had a low level of hemoglobin, all fish had an insufficient number of red blood cells in the blood; in Russian sturgeon, a high level of pathologically altered erythrocytes was determined, the amount of serum protein was increased, deviations were found in the ratio of its fractions, high levels of uric acid, low levels of triglycerides, β-lipoproteins, ALT and AST activity in the blood. Indirectly, these changes in the physiological state of sturgeon fish with nephrocalcinosis indicate that this disease most likely arose as a result of the influence of a complex of factors on the fish, among which the main ones may be disturbances in the hydrochemical regime and the balance of feeding.

Dietary inclusion of black soldier fly (Hermetia illucens) larvae meal, with exogenous protease supplementation, in practical diets for striped catfish (Pangasius hypophthalmus, Sauvage 1878).

Fishmeal (FM) is a key component of commercial fish feeds, but due its unsustainable supply, the search for quality alternatives of FM has become a significant area of investigation worldwide. The insect-based proteins such as black soldier fly larvae (BSFL) are being recognized as an alternative ingredient. However, anti-nutritional factors in these alternatives may negatively affect nutrient utilization in fish. Incorporating exogenous protease enzymes as feed additives could be a promising way to improve the digestibility of these alternative ingredients. Therefore, this study aimed to evaluate the impact of dietary inclusion of BSFL meal, combined with protease supplementation, on various parameters of striped catfish (Pangasius hypophthalmus). Five diets were formulated: a control diet (FM-based), two diets with 30% and 60% BSFL inclusion (BSF30 and BSF60), and two diets with the same inclusion levels plus the incorporation of exogenous protease (BSF30P and BSF60P). One hundred fifty fish (8.26±0.02 g) were arbitrarily allocated to five groups, each with three replicates. The fish were provided with their respective diets twice per day for 60 days. In comparison to the control, fish-fed diets supplemented with protease demonstrated statistically significant lower levels of feed conversion ratio and higher growth performance regarding the final body weight and weight gain. Lipase activity in the BSF60P group was notably greater than in the control group. Protease supplementation significantly enhanced the apparent digestibility coefficient of protein, intestinal protease activity, and crude protein content in the whole body. Most hematological and biochemical parameters remained unaffected except for substantially lower triglyceride and cholesterol levels in the highest BSFL inclusion groups. These groups also showed a reduction in crude fat contents. While glutathione peroxidase and malondialdehyde levels did not change significantly from the control, the liver tissues of fish fed BSF60P diets showed considerably higher levels of antioxidant enzymes such as catalase and superoxide dismutase. The findings suggest that including 60% of a BSFL based diet, along with exogenous protease supplementation, is feasible without compromising the growth performance and health of striped catfish.

Analyzing lipid profiles and dyslipidemia prevalence in hypertensive patients: a cross-sectional study from primary community health institutions

BackgroundA significant proportion of hypertensive patients also suffer from comorbid dyslipidemia, which critically influences their treatment outcomes and overall prognosis. Given its implications, the lipid profiles of hypertensive individuals warrant increased attention for more effective clinical management.MethodsWe analyzed data from 92,443 hypertensive patients registered at primary community health institutions in 2021. Employing a cross-sectional study design, we assessed the distribution of lipid levels and the prevalence of various dyslipidemia subtypes. Stepwise forward logistic regression was used to identify factors associated with dyslipidemia, adjusting for gender, age, body size, and other relevant characteristics.ResultsAccording to the 2023 Chinese Guidelines for the Management of Lipids, the overall prevalence of dyslipidemia was 37.5%. Subtype analysis revealed prevalence of high total cholesterol (TC) at 11.2%, high triglycerides (TG) at 16.0%, low high-density lipoprotein cholesterol (HDL-C) at 16.0%, and high low-density lipoprotein cholesterol (LDL-C) at 10.2%. TG abnormalities were more common among males (16.8%), whereas TC abnormalities predominated in females (14.4%). Notably, hypertensive patients with diabetes had higher levels of TG compared to non-diabetics (p = 0.009). Those with stroke and liver disease comorbidities exhibited lower TG levels than their counterparts (p = 0.018 and p < 0.001, respectively). Additionally, HDL-C levels were significantly lower in hypertensives with diabetes, coronary artery disease, and central obesity (p < 0.001, p = 0.026, p < 0.001, respectively). Regression analysis indicated that dyslipidemia prevalence correlates significantly with gender, age, diabetes, coronary heart disease, stroke, family history of hypertension, body mass index (BMI), central obesity, frequency of physical activity, smoking status, regular alcohol consumption, and abdominal ultrasound findings.ConclusionOur study underscores the necessity of rigorous lipid monitoring and analysis of dyslipidemia-influencing factors for the development of effective health management strategies within the community. There is a critical need to examine lipid profiles comprehensively and implement targeted therapeutic interventions aimed at managing hyperlipidemia, a modifiable risk factor for cardiovascular disease.

Impact of Apple Cider Vinegar on Insulin Resistance and Related Conditions: Benefits, Mechanisms, and Potential Risks - Literature Review

Introduction and purpose: The topic of apple cider vinegar supplementation and insulinresistance is becoming increasingly widespread, especially on the internet, which carriesmany potential risks. There is a need to understand both how apple cider vinegar reducesinsulin resistance and improves metabolic parameters, as well as the potential risks of its use.Material and methods: Medical databases like PubMed, Google Scholar, and Embase weresearched for scientific papers on the safety, benefits, mechanisms, and risks of apple cidervinegar in insulin resistance and related conditions. These were analyzed and summarized ina single review.State of knowledge: Apple cider vinegar supplementation contributes to a reduction ininsulin resistance, which is reflected in parameters such as decreased postprandial insulinsecretion, lower levels of triglycerides (TG) and total cholesterol (TC), reduced fastingglucose, lower HbA1c levels, and supports weight loss, potentially improving insulinsensitivity. In most cases, no adverse effects or serious side effects were observed with dosesof 15-30 ml per day. However, potential risks include delayed gastric emptying, exacerbationof gastroesophageal reflux disease (GERD), gastrointestinal disturbances, tooth erosion,although one study suggests that such supplementation may be associated with acutepancreatitis.Conclusions: More research is needed on supplementation, particularly regarding itsduration. Another risk is the search for health information online without critically evaluatingthe content. Weight loss through a proper diet and exercise appears to be key for improvinginsulin sensitivity, but supplementation may help achieve results in certain patient groups.

Five-Year Incidence of Age-Related Macular Degeneration and Its Risk Factors in Adult Chinese Population: The Tongren Health Care Study.

To examine the 5-year incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population. The Tongren Health Care Study included individuals attending regular health care check-up examinations in the Beijing Tongren Hospital. Baseline examinations were performed from 2014 to 2015, with 5-year follow-up examinations conducted between 2019 and 2020. Fundus photographs were graded according to the Beckman Initiative guidelines. A total of 5658 participants with gradable photographs at both examinations were included in the study, comprising 58.0% women, with a mean age of 54.9 ± 11.0years. The 5-year incidence of any, early, intermediate, and late AMD were 6.1% (95% confidence interval [CI], 5.5%-6.8%), 5.0% (95% CI, 4.4%-5.6%), 3.4% (95% CI, 2.9%-3.9%), and 0.3% (95% CI, 0.2%-0.4%), respectively. In multivariate analysis, incident early AMD was associated with older age (P < 0.001; odds ratio [OR], 1.04; 95% CI, 1.02-1.06), female sex (P = 0.011; OR, 1.42; 95% CI, 1.08-1.86), and a higher estimated glomerular filtration rate (P = 0.020; OR, 1.15; 95% CI, 1.02-1.30), whereas having diabetes was a protective factor (P = 0.019; OR, 0.61; 95% CI, 0.41-0.92). Incident intermediate AMD was associated with older age (P < 0.001; OR, 1.05; 95% CI, 1.04-1.07), a higher high-density lipoprotein cholesterol level (P < 0.001; OR, 1.97; 95% CI, 1.38-2.83) and a lower triglyceride level (P = 0.008; OR, 0.77; 95% CI, 0.64-0.93). A higher estimated glomerular filtration rate level was a risk factor for incident early AMD. A higher high-density lipoprotein cholesterol level and lower triglyceride level were risk factors for incident intermediate AMD. This finding may point to the role of renal circulation and lipid metabolism in incident AMD. This community-based longitudinal study may provide a valuable understanding of AMD and its associated factors for targeted prevention and management strategies.

ASGR1 deficiency improves atherosclerosis but alters liver metabolism in ApoE-/- mice

The asialoglycoprotein receptor 1 (ASGR1), a multivalent carbohydrate-binding receptor that primarily is responsible for recognizing and eliminating circulating glycoproteins with exposed galactose (Gal) or N-acetylgalactosamine (GalNAc) as terminal glycan residues, has been implicated in modulating the lipid metabolism and reducing cardiovascular disease burden. In this study, we investigated the impact of ASGR1 deficiency (ASGR1−/−) on atherosclerosis by evaluating its effects on plaque formation, lipid metabolism, circulating immunoinflammatory response, and circulating N-glycome under the hypercholesterolemic condition in ApoE-deficient mice. After 16 weeks of a western-type diet, ApoE−/−/ASGR1−/− mice presented lower plasma cholesterol and triglyceride levels compared to ApoE−/−. This was associated with reduced atherosclerotic plaque area and necrotic core formation. Interestingly, ApoE−/−/ASGR1−/− mice showed increased levels of circulating immune cells, increased AST/ALT ratio, and no changes in the N-glycome profile and liver morphology. The liver of ApoE−/−/ASGR1−/− mice, however, presented alterations in the metabolism of lipids, xenobiotics, and bile secretion, indicating broader alterations in liver homeostasis beyond lipids. These data suggest that improvements in circulating lipid metabolism and atherosclerosis in ASGR1 deficiency is paralleled by a deterioration of liver injury. These findings point to the need for additional evaluation before considering ASGR1 as a pharmacological target for dyslipidemia and cardiovascular disorders.Graphical abstract

Metabolic syndrome in association with novel dietary index, metabolic parameters, nesfatin-1 and omentin-1

BackgroundMetabolic syndrome is a prevalent and common health problem and numerous studies have revealed the role of diet and lifestyle change in prevention of metabolic syndrome. However, the novel dietary index, cardioprotective index (CPI) and its association with metabolic syndrome is not investigated yet. In the current study, we evaluated the association between metabolic syndrome and its components, CPI, Nesfatin-1 and Omentin-1in a cross-sectional study.MethodsThree hundred forty eight overweight and obese individuals with metabolic syndrome were recruited. Subjects underwent anthropometric and laboratory assays including metabolic markers, Nesfatin-1 and Omentin-1 with commercial kits.ResultsThose at the first tertile of CPI had lower high density lipoprotein concentrations (HDL) and higher low density lipoprotein concentrations (LDL), triglyceride (TG), systolic and diastolic blood pressures (SBP, DBP) levels compared with those at the highest tertiles (P < 0.05). After adjustment for the confounding effects of age, sex, body mass index, physical activity and total calorie intake, LDL lost its significance across CPI tertiles. Moreover, serum total cholesterol, insulin and insulin resistance were not significant across CPI tertiles neither in crude nor in adjusted models (P > 0.05). Additionally, being at the third tertile of CPI was accompanied with significantly higher Nesfatin-1 and Omentin-1 levels compared with lowest tertiels (P < 0.05) in crude and confounder – adjusted models. Conclusions: To our findings, CPI was in positive relationship with metabolic parameters, blood pressure, Nesfatin-1 and Omentin-1 levels in metabolic syndrome. Further future studies will help to elaborate the causality.Clinical trial numberNot applicable.

Association Between Lifestyle Patterns and Abdominal Obesity with Biochemical and Inflammatory Biomarkers in Adolescents with Down Syndrome: The UP&DOWN Study.

The main objective of this study was to examine the association between lifestyle patterns (physical activity, screen and sleep time and diet) and abdominal obesity, and endocrine, metabolic, and immunological biomarkers in adolescents with Down syndrome (DS). Eighty-three DS adolescents (38.6% girls), aged 11 to 18 years, from the UP&DOWN study were included. Cluster analysis was performed by including the compliance of recommendations of lifestyle variables, such as moderate to vigorous physical activity (MVPA), screen and sleep time and adherence to the Mediterranean diet (AMD). The waist-to-height ratio was used as an indicator of abdominal obesity. Haematological, biochemical and inflammatory biomarkers were analysed. A three-cluster solution was identified: Cluster 1: adolescents with low compliance; Cluster 2: youth with medium compliance; and Cluster 3: adolescents with high compliance. Significant differences in MVPA (p = 0.000), screen time (p = 0.004), sleep time (p = 0.0001), AMD (p = 0.000) and abdominal obesity (p = 0.003) were found. Clusters 2 and 3 had lower levels of triglycerides and LDL-cholesterol than Cluster 1. Cluster 2, in which all adolescents met the MVPA recommendations, had the lowest levels of galactin 3. Compliance with lifestyle recommendations (PA, screen and sleep time and AMD) and the absence of abdominal obesity seem to be associated with better biochemical and inflammatory values.

Abstract 4137713: Epsin-Mediated PCSK9-LDLR Interaction: A New Therapeutic Target for Atherosclerosis

Introduction: Atherosclerosis, a leading cause of cardiovascular diseases, causes about 17.9 million deaths annually. It is driven by high levels of LDL cholesterol (LDL-C). The liver's LDL receptor (LDLR) removes LDL-C from the bloodstream, but its degradation by PCSK9 exacerbates the condition. Epsin, an endocytic adaptor protein crucial for clathrin-mediated endocytosis, plays a significant role in atherosclerosis, particularly lipid metabolism. Hypothesis: We propose that hepatic epsins significantly contribute to atherosclerosis by facilitating the PCSK9-induced degradation of LDLR, thus impeding LDL-C clearance. Objectives: This study aims to investigate hepatic epsins' role in PCSK9-mediated LDLR degradation and its effects on LDL-C levels and atherosclerosis development. Using bioinformatics, we will analyze enriched pathways and networks to study epsins modulation, which will be validated through biochemical assays and in vivo experiments. Methods: Liver-specific double knockout (DKO) mice lacking epsin1 and epsin2 were created on an ApoE -/- background. Atherosclerosis was induced using a Western diet (WD), and blood cholesterol and triglyceride levels were monitored. We employed high-resolution single-cell RNA sequencing (scRNA-seq) to analyze cellular transitions, intercellular interactions, and Gene Ontology pathway enrichment within hepatocyte-derived data. Results: RNA velocity reveals the transition from lipogenic Alb hi Hepatocytes to glucogenic Hnf4a hi Hepatocytes in Liver-DKO mice on an ApoE -/- background on a WD. Liver-DKO mice on an ApoE -/- background on a WD exhibited significantly reduced atherogenesis and lower blood cholesterol and triglyceride levels compared with wild-type on an ApoE -/- background on a WD. Gene Ontology enrichment analysis showed elevated pathways for LDL particle clearance and enhanced LDLR-cholesterol communication scores in Liver-DKO mice, suggesting improved LDL-C clearance. Nanoparticle-encapsulated siRNAs targeting liver epsins effectively inhibited atherosclerosis. Conclusion: Epsin depletion in the liver upregulated LDLR protein levels, and PCSK9-triggered LDLR degradation was abolished, preventing atheroma progression. Targeting liver epsins presents a novel therapeutic strategy for atherosclerosis, supported by network analysis and predictive modeling for effective interventions.

Abstract 4146303: A Single-Dose of a Novel CasX-Editor Lowers APOC3 Levels In Vivo

Background: Apolipoprotein C-III (APOC3) is a key regulator of lipid metabolism that inhibits the catabolism and clearance of triglyceride (TG)-rich lipoproteins in the blood. Loss-of-function APOC3 variants are associated with significantly lower TG levels and a reduced risk of heart disease, underscoring the potential of APOC3 inactivation as a therapeutic strategy for patients with familial chylomicronemia syndrome (FCS) and severe hypertriglyceridemia (SHTG). Here, we developed STX-1400 lead molecules as a novel investigational gene editing treatment using a highly engineered CRISPR-CasX mRNA and a guide RNA (gRNA) encapsulated into lipid nanoparticles (LNPs) to edit the APOC3 gene and knock out its hepatic expression. Methods: STX-1400 lead molecules were evaluated for editing potency and resulting functional effects on APOC3 reduction in vitro in primary human hepatocytes (PHHs) and primary cynomolgus hepatocytes (PCHs). In vivo studies were conducted in PXB mice, a humanized liver mouse model. Liver biopsies and serum samples were collected at two weeks post-dose. Human APOC3 mRNA and APOC3 protein levels were measured in liver biopsies and serum samples, respectively. Lipid profile evaluation, which included measuring TGs and total cholesterol (TC) levels, was also performed. Results: Treatment of PHHs with LNPs containing STX-1400 lead molecules showed a dose-dependent increase in editing activity; up to 90% editing at the APOC3 locus was associated with &gt;70% reduction in secreted APOC3 protein levels. Potency was also observed in PCHs, with up to 70% editing. A single dose of LNPs encapsulating STX-1400 lead molecules delivered into PXB humanized mice resulted in &gt;60% editing at the APOC3 locus in the liver, which was associated with &gt;90% reduction of serum hAPOC3 protein levels, accompanied by reduction in TG and TC levels. Conclusions: These data demonstrate that the STX-1400 lead molecules efficiently knock down hepatic expression of APOC3 in preclinical models. This work suggests that the CRISPR-CasX-based editor approach could be developed as a single dose therapy for the treatment of hypertriglyceridemia.

Cardiometabolic risk factors are affected by interaction between FADS1 rs174556 variant and dietary vegetable oils in patients with diabetes: a randomized controlled trial

FADS1 rs174556 polymorphism influences on dietary fats metabolism and type 2 diabetes (T2DM). This study aimed to compare the effect of three oils of sesame, canola and sesame-canola on cardio metabolic factors across genotypes of rs174556 variant in patients with type 2 of diabetes. This study was a randomized triple-blind three-way cross-over clinical trial. 95 Subjects with T2DM replaced their regular dietary oil with sesame oil, canola oil, or sesame-canola oil for three 9-week phases and completed the study. There were three anthropometric measurements, blood sampling and biochemical assessments at the beginning, middle, and at the end of each phase for assessments. Genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method. In the crude model, there was an interaction between consumed oils and rs174556 variant on serum concentration of Apolipoprotein A-I (ApoA-1). During intake of sesame oil, lower levels of triglycerides (TG) were observed in individuals with TT genotype compared to C allele carriers’ allele, which remained significant in adjusted models. Compared to C allele carrier’s, the people with TT genotype experienced significant increase and decrease in serum levels of HDL and TG, respectively in adjusted models. Also, the subjects who consumed sesame-canola oil had lower serum concentrations of fasting blood glucose than those who received sesame and canola oils, regardless of used oils and genotypes. FADS1 Gene variant (rs174556) might modify cardiometabolic changes following dietary vegetable oils. Larger longitudinal studies especially randomized clinical trials are needed to clarify these associations.

Improvements in Insulin Resistance and Glucose Metabolism Related to Breastfeeding Are Not Mediated by Subclinical Inflammation.

Background: Lactation is known to improve insulin resistance, but this phenomenon remains poorly understood. Our goal was to evaluate whether subclinical inflammation could mediate the association between breastfeeding (BF) and improvement in glucose metabolism and markers of insulin resistance (MIRs) in the postpartum. Methods: A total of 95 adult women (≥18 years) with a BMI ≥ 25 kg/m2 from the outpatient clinic of the Federal University of São Paulo were followed from early pregnancy until 60 to 180 days postpartum. The patients were divided based on their BF status: BF and non-BF groups. A latent variable termed SubInf was created incorporating inflammation-related biomarkers: adiponectin, E-selectin, branched-chain amino acids, zonulin, copeptin, and lipopolysaccharides. The association of BR with MIRs in the postpartum was evaluated through linear regression analysis, and mediation analysis was performed to evaluate the role of SubInf in this association. Results: The groups were similar regarding gestational diabetes mellitus (GDM) prevalence, pre-gestational BMI, caloric intake, physical activity, and postpartum weight loss. The BF group presented lower levels of triglycerides (TGs), fasting glucose, fasting insulin, TG/HDLcholesterol ratio (TG/HDL), TyG index, and HOMA-IR compared to the non-BF group. A linear regression analysis adjusted for scholarity, parity, pre-gestational BMI, GDM, weight gain during pregnancy, and mode of delivery revealed an inverse association between BF and fasting glucose [-6.30 (-10.71 to -1.89), p = 0.005), HOMA-IR [-0.28 (-0.50 to -0.05), p = 0.017], TyG index [-0.04 (-0.06 to -0.01), p = 0.002], and TG/HDL ratio [-0.23 (-0.46 to -0.01), p = 0.001]. In the mediation analysis, SubInf did not mediate the indirect effect of BF on MIRs. Conclusions: In overweight and obese women, an association between BF and improvement in MIRs in the postpartum was seen, corroborating that BF should be stimulated, especially in these cardiometabolic high-risk women. Subclinical inflammation did not seem to mediate this association.

Increased risk of vascular complications in patients with type 2 diabetes and fatty liver disease

BackgroundThe prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM.MethodsInpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1.ResultsOf the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis.ConclusionHepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications.

Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial.

Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.

Organophosphorus Flame Retardants and Metabolic Disruption: An in Silico, in Vitro, and in Vivo Study Focusing on Adiponectin Receptors.

Environmental chemical exposures have been associated with metabolic outcomes, and typically, their binding to nuclear hormone receptors is considered the molecular initiating event (MIE) for a number of outcomes. However, more studies are needed to understand the influence of such exposures on cell membrane-bound adiponectin receptors (AdipoRs), which are critical metabolic regulators. We aimed to clarify the potential interactions between AdipoRs and environmental chemicals, specifically organophosphorus flame retardants (OPFRs), and the resultant effects. Employing in silico simulation, cell thermal shift, and noncompetitive binding assays, we screened eight OPFRs for interactions with AdipoR1 and AdipoR2. We tested two key events underlying AdipoR modulation upon OPFR exposure in a liver cell model. The Toxicological Prioritization Index (ToxPi)scoring scheme was used to rank OPFRs according to their potential to disrupt AdipoR-associated metabolism. We further examined the inhibitory effect of OPFRs on AdipoR signaling activation in mouse models. Analyses identified pi-pi stacking and pi-sulfur interactions between the aryl-OPFRs 2-ethylhexyl diphenyl phosphate (EHDPP), triphenyl phosphate (TPhP), and tricresyl phosphate (TCP) and the transmembrane cavities of AdipoR1 and AdipoR2. Cell thermal shift assays showed a rightward shift in the AdipoR proteins' melting curves upon exposure to these three compounds. Although the binding sites differed from adiponectin, results suggest that aryl-OPFRs noncompetitively inhibited the binding of the endogenous peptide ligand ADP355 to the receptors. Analyses of key events underlying AdipoR modulation revealed that glucose uptake was notably lower, whereas lipid content was higher in cells exposed to aryl-OPFRs. EHDPP, TCP, and TPhP were ranked as the top three disruptors according to the ToxPi scores. A noncompetitive binding between these aryl-OPFRs and AdipoRs was also observed in wild-type (WT) mice. In db/db mice, the finding of lower blood glucose levels after ADP355 injection was diminished in the presence of a typical aryl-OPFR (TCP). WT mice exposed to TCP demonstrated lower AdipoR1 signaling, which was marked by lower phosphorylated AMP-activated protein kinase (pAMPK) and a higher expression of gluconeogenesis-related genes. Moreover, WT mice exposed to ADP355 demonstrated higher levels of pAMPK protein and peroxisome proliferator-activated receptor- messenger RNA. This was accompanied by higher glucose disposal and by lower levels of long-chain fatty acids and hepatic triglycerides; these metabolic improvements were negated upon TCP co-treatment. In silico, in vitro, and invivo assays suggest that aryl-OPFRs act as noncompetitive inhibitors of AdipoRs, preventing their activation by adiponectin, and thus function as antagonists to these receptors. Our study describes a novel MIE for chemical-induced metabolic disturbances and highlights a new pathway for environmental impact on metabolic health. https://doi.org/10.1289/EHP14634.

Sodium Orthovanadate Mitigates Nonalcoholic Fatty Liver Disease by Enhancing Autophagy.

Sodium orthovanadate (SOV) has been investigated in recent research for its therapeutic efficacy in treating metabolic disorders. Considering the rising prevalence of non-alcoholic fatty liver disease (NAFLD), the effects of SOV on NAFLD remain to be further investigated. The aim of this study was to investigate the role and mechanism of SOV in NAFLD. Two mouse models were established by induction with high fat diet (HFD) and Western diet supplemented with the sugar in drinking water (WDS), respectively. We searched for the downstream molecules of SOV by RNA sequencing, followed by rescue experiments with an autophagy inhibitor (3-MA) in HepG2 cells as well as in animal models. The results showed that in HFD and WDS-induced NAFLD models, SOV significantly reduced body weight, inhibited lipid deposition, lowered serum triglyceride and cholesterol levels. Then RNA sequencing and RT-PCR found that the effect of SOV might be related to the activation of autophagy coregulated by hypoxia-inducible factor 1 and autophagy-related gene 5. The protective effects of SOV-activated autophagy were blocked by 3-MA, leading to the restoration of lipid deposition in vitro and in vivo. We conclude that SOV could activate liver cell autophagy, thereby improving lipid deposition and metabolism during the course of NAFLD. Our findings revealed the potential of SOV for controlling NAFLD.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Growth performance, serum metabolites, plasma protein fraction, meat lipid profile and antioxidant activities of breast meat of broiler chicken fed diets containing Cinnamomum ceylon powder, Zingiber officinale powder and Moringa oleifera leafmeal supplem

An experiment was conducted to determine growth performance, serum metabolites, plasma protein fraction, meat lipid profile and antioxidant activities of meat of broilers as affected by Cinnamomium ceylon, Zingiber officinale and Moringa oleifera supplementation. A total of 112 day old chicks were allotted into four treatments replicated four times with seven birds per replicate in a completely randomized design (CRD). Basal diets were formulated for broiler starters (0-28days) and finisher phase (29-56) days. The basal diets were divided into 4 diets : diet 1- control diet without supplementation; diet 2- contained 0.2% Cinnamomum ceylon supplementation (CCS); diet 3- contained 0.2% Zingiber officinale supplementation (ZOS), diet 4-contained 0.2% Moringa oleifera leafmeal (MOLM) supplementation. The experiment lasted for 56 days. Results showed an improvement in final liveweight, weight gain, feed intake and feed conversion ratio of birds on 0.2% MOLM. Birds on phytogenic feed additives have lower values of urea, cholesterol, glucose, high density lipoprotein and low density lipoprotein. Birds administered phytogenic supplements exhibited much greater plasma albumin levels. Low levels of meat cholesterol, triglycerides and low density lipoprotein were found in birds fed phytogenic feed additives while high levels of high density lipoprotein were recorded for birds on phytogenic feed additives. The supplementation of broilers diets with phytogenic feed additives increased the glutathione peroxidase and superoxide dismutase and decreased lipid peroxidation. It was concluded that supplementation of broiler diets with Moringa oleifera leaf meal enhanced body weight gain, antioxidant activities also reduced cholesterol level in both serum metabolites and meat.

Impact of Triglyceride Levels on the Long-term Clinical Outcomes in Patients With Acute Myocardial Infarction.

Hypertriglyceridemia is a known cardiovascular risk factor. However, the relationship between serum triglyceride (TG) levels and the clinical outcomes in patients with acute myocardial infarction (AMI) is unclear. We conducted a single-center, retrospective observational study involving 538 consecutive patients with AMI who underwent emergent percutaneous coronary intervention within 12 hours of onset. Patients were categorized into three groups based on their serum TG levels at admission as follows: T1 group (TG <78 mg/dl, n=172), T2 group (78≤TG<141 mg/dl, n=177), and T3 group (141 mg/dl ≤TG, n=176). The primary endpoint was major adverse cardiovascular events (MACEs) defined as a composite of cardiovascular death, non-fatal MI, and non-fatal stroke. The median follow-up period was 2.4 (1.5-4.2) years. Patients in the T1 group were older, had a higher proportion of females, and had fewer cardiovascular risk factors. However, they also had a higher prevalence of multi-vessel coronary artery disease and severely calcified culprit lesions. The T1 group had a significantly higher rate of MACEs (20.4% in T1, 12.4% in T2 and 8.5% in T3, p<0.05 by Log-rank test, respectively). Multivariate analysis revealed that T1 was an independent predictor of MACEs (hazard ratio=2.19, 95% confidence interval=1.16-4.14, p<0.05). Although patients with AMI with low TG levels at admission had fewer coronary risk factors, they had more severe calcified culprit lesions and worse clinical outcomes.

Efficacy and severity of side-effects of rosuvastatin compared to other statins post-heart-transplantation

Abstract Introduction The International Society of Heart and Lung Transplantation (ISHLT) 2022 guideline recommends statin therapy in heart transplantation (HTx) patients, with the therapeutic low-density lipoprotein (LDL) target being &amp;lt;2.5 mmol/L. Particularly pravastatin is recommended, given proven beneficial effects on long-term clinical outcome and the low prevalence of side effects. Yet, in the general population, rosuvastatin has been shown to be even more potent. Purpose We investigated the lipid-lowering effect and severity of side-effects of rosuvastatin compared to less potent statins in HTx patients. Methods In this before-after study, we included all HTx patients whom were prescribed a change from the statin they were using to rosuvastatin, for better cardiovascular risk management and/or because of side-effects, between February 2018 and February 2023. We evaluated the weight, lipid profile and side-effects (including myalgia, cramps, stiffness and weakness) of these patients up to one year prior to and after the statin change. At the same time, side-effects were measured in a visual analogue scale (VAS) ranging from 0-10, with the average score of side-effects utilized for analysis. We compared the differences using a Wilcoxon signed rank test. Results Out of 299 HTx patients, we included 114 patients, with a median age of 58 [IQR 50-67] years at switch of whom 31 (27%) were females. Median time since HTx was 9 [IQR 5-15] years. The distribution and dosage of prescribed statins before and after switch can be found in Table 1. Compared to statins used prior to therapy change, rosuvastatin was associated with lower total cholesterol, LDL- and triglyceride levels, with high density lipoprotein (HDL) levels remaining the same (Table 2). No difference in bodyweight was found (Table 2). Before switch, 41 (36%) patients achieved the target of LDL-levels below 2.5 mmol/L. After switch, 86 (75%) patients achieved the target of LDL levels below 2.5 mmol/L. Rosuvastatin shows a trend towards a lower prevalence of side-effects (Table 2). Conclusion In HTx patients that were prescribed a change of statin due to better cardiovascular risk management and/or complaints of side-effects, rosuvastatin is related to a more favorable lipid profile, without additional side-effects, compared to other statins. Furthermore, many more patients achieve the guideline recommended LDL-target. Ongoing research should determine whether this translates to a better clinical outcome.