Blood Triglyceride Levels Research Articles

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 4113300: Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis

Rationale: Low density cholesterol receptor (LDLR) in the liver is critical for the clearance of low-density lipoprotein cholesterol (LDL-C) in the blood. In atherogenic conditions, proprotein convertase subtilisin/kexin 9 (PCSK9) binds to LDLR on the surface of hepatocytes, preventing its recycling and enhancing its degradation in lysosomes, resulting in reduced LDL-C clearance. Our recent studies demonstrate that epsins, a family of ubiquitin-binding endocytic adaptors, are critical regulators of atherogenicity. Given the fundamental contribution of circulating LDL-C to atherosclerosis, we hypothesize that liver epsins promote atherosclerosis by controlling PCSK9-triggered LDLR endocytosis and degradation. Objective: We will determine the role of liver epsins in promoting PCSK9-mediated LDLR degradation and hindering LDL-C clearance to propel atherosclerosis. Methods and Results: We generated double knockout mice using albumin Cre in which both genes of epsin, namely, epsin 1 and epsin 2, are specifically deleted in the liver (Liver-DKO) on an ApoE -/- background. We discovered that western diet (WD)-induced atherogenesis was greatly inhibited, along with diminished blood cholesterol and triglyceride levels. Mechanistically, using scRNA-seq analysis on hepatocyte-derived data revealed elevated pathway involved in LDL particle clearance under WD treatment in ApoE -/- /Liver-DKO, which was coupled with diminished plasma LDL-C levels. Further analysis using the MEBOCOST algorithm revealed enhanced communication score between LDLR and cholesterol, suggesting elevated LDL-C clearance in the ApoE -/- Liver-DKO mice. In addition, we showed that loss of epsins in the liver upregulates of LDLR protein level. We further showed that epsins bind LDLR via the ubiquitin-interacting motif (UIM), and PCSK9-triggered LDLR degradation was abolished by depletion of epsins, preventing atheroma progression. Finally, our therapeutic strategy, which involved targeting liver epsins with nanoparticle-encapsulated siRNAs, was highly efficacious at inhibiting dyslipidemia and impeding atherosclerosis. Conclusions: Liver epsins promote atherogenesis by mediating PCSK9-triggered degradation of LDLR, thus raising the circulating LDL-C levels. Targeting epsins in the liver may serve as a novel therapeutic strategy to treat atherosclerosis by suppression of PCSK9-mediated LDLR degradation.

Ethnopharmacological Importance of Gymnema sylvestre

Gymnema sylvestre is one of the valuable medicinally important herbs that belong to family Apocynaceae. G. Sylvester is a woody climber mostly found in India, Srilanka, China, Indonesia, Malaysia and Tropical Africa. Traditionally the leaf of the herb is used as antidiabetic, antihelmentic, antiobesity, anti-inflammatory, hypolipidaemic, antivenom and antimicrobial. The herb is used by some ethnic community in constipation, haemorrhoids, jaundice, leucoderma, asthma, bronchitis, cardiac problems and dyspepsia. Most important phytochemicals of the plant are gymnemic acid, deacyl gymnemic acid and gymnemagenol which help in the controlling of blood cholesterol, triglyceride levels, inflammation and body weight. The present review aims to document the traditional and modern pharmacological uses of the plant to provide better scope for further experiments and future application. The botanical description, cultivation practices, phytochemical constituents and safety issues of the plant has also been described in the chapter.

Relationship between physical activity and abdominal obesity and metabolic markers in postmenopausal women

This study aimed to investigate the impact of physical activity indicators monitored by the POLAR accelerometer on body obesity indicators, metabolic syndrome parameters, and energy metabolism hormones in postmenopausal women. Was included 71 participants from this study program (68.8 ± 4.3 years). We divided participants into LPA and MVPA groups based on their level of moderate to vigorous physical activity per week; Physical activity levels over 7 days were assessed using a POLAR accelerometer, with daily step counts and sedentary time recorded. Measurements included waist circumference, visceral fat volume, body fat percentage, blood pressure, fasting blood glucose, triglyceride levels, HDL cholesterol, and energy metabolism hormone levels (leptin, resistin, adiponectin). The MVPA group displayed lower waist circumference, body fat percentage, abdominal fat, and BMI compared to the LPA group (p < 0.05). A significant negative correlation was observed between daily step count and obesity indicators, including waist circumference (r = -0.301), body fat percentage (r = -0.295), abdominal fat (r = -0.318), and BMI (r = -0.238). Conversely, sedentary time showed a positive correlation with obesity indicators such as waist circumference (r = 0.258), body fat percentage (r = 0.239), and abdominal fat (r = 0.244). Moreover, daily step count exhibited a significant negative correlation with leptin levels (r = -0.245), while sedentary time was positively correlated with the energy metabolic factor leptin (r = 0.279). Waist circumference demonstrated significant positive correlations with triglycerides, blood glucose, adiponectin, resistin, and leptin levels. Postmenopausal women who engage in at least 150 min of MVPA weekly show lower obesity indices. There is a significant correlation between physical activity levels and obesity indicators, which relate to metabolic syndrome and energy metabolism factors. Thus, increased physical activity may help prevent metabolic syndrome and cardiovascular diseases in this population.

Relationship Between The Incidence Of Hypertension And Triglyceride Levels In Bus Drivers At Arjosari Terminal, Malang City

Hypertension is a health problem that is widely encountered in the community and correlates with other diseases. There are many factors that cause hypertension, one of which is abnormal triglyceride levels or hypertriglycerides. Higher levels of triglycerides will inhibit the occurrence of lipogenesis. Lipogenesis is a factor that causes hypertension from food intake, this is because food has a significant role in increasing blood pressure, especially protein and fat. This study aims to determine the relationship between triglyceride levels and hypertension. This type of research is an analytical research with the crosssectional method, statistical data analysis using correlation regression, the number of population as many as 50 respondents and the sample used as many as 21 respondents. Data collection using questionnaires, blood pressure measurements and triglyceride level checks. Blood pressure measurement is done manually and then for the examination of triglyceride levels using the GPO-PAP method is carried out in the laboratory of the Bareng Health Center using a spectrophotometer. The statistical analysis used is the correlation Pearson test. The results of the study on bus drivers with high blood pressure showed that some respondents had high triglyceride levels because they often ate fatty foods. Based on the examination that has been carried out on 21 bus driver respondents at the Arjosari Terminal, Malang City, it shows that triglyceride levels and high blood pressure have no relationship, with the test results using the Pearson correlation statistical test obtained a result of P=0.0766 0.05 with a Pearson value of P=-0.069 correlation meaning that it does not have a relationship with the degree of very weak relationship.

Cardiometabolic characteristics of weight cycling: results from a mid-South regional comprehensive health care system.

The objective of this study was to determine the unique clinical and cardiometabolic risk characteristics of weight-cyclers and identify differences between weight-cyclers and individuals with other weight-change trajectories. A deidentified database of 1,428,204 Vanderbilt University Medical Center patients from 1997 to 2020 was included based on having ≥5 years of recorded weights. Patients with a history of malignant neoplasm, bariatric surgery, implausible BMI (e.g., <15 or >80 kg/m2), or missing documented height were excluded, yielding 83,261 participants categorized by weight trajectory, i.e., weight-stable, weight-gainer, weight-loser, or weight-cycler, based on criteria of ≥5% weight-change thresholds. Additionally, quartiles of average successive weight variability were evaluated to determine the effect of absolute differences among successive weight values. Over half (55%) of participants were weight-cyclers, 23% were weight-gainers, 12% were weight-losers, and 10% were weight-stable over 5 years. Although baseline BMI did not differ among groups, weight-cyclers were more likely to have lower high-density lipoprotein cholesterol and higher blood glucose and triglyceride levels and to have been prescribed antihypertensive, dyslipidemia, and/or antidiabetic therapies. They were also younger and more likely to be smokers. Participants with the greatest weight variability (i.e., highest quartile of average successive weight variability) had higher cardiometabolic risk scores. Weight cycling was highly prevalent but yielded no meaningful overall change in body weight after 5 years. These findings support a paradigm shift in weight management in individuals with overweight/obesity toward reducing cardiometabolic risk with or without weight loss.

Effects of Phenolic Acids Produced from Food-Derived Flavonoids and Amino Acids by the Gut Microbiota on Health and Disease.

The gut microbiota metabolizes flavonoids, amino acids, dietary fiber, and other components of foods to produce a variety of gut microbiota-derived metabolites. Flavonoids are the largest group of polyphenols, and approximately 7000 flavonoids have been identified. A variety of phenolic acids are produced from flavonoids and amino acids through metabolic processes by the gut microbiota. Furthermore, these phenolic acids are easily absorbed. Phenolic acids generally represent phenolic compounds with one carboxylic acid group. Gut microbiota-derived phenolic acids have antiviral effects against several viruses, such as SARS-CoV-2 and influenza. Furthermore, phenolic acids influence the immune system by inhibiting the secretion of proinflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α. In the nervous systems, phenolic acids may have protective effects against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Moreover, phenolic acids can improve levels of blood glucose, cholesterols, and triglycerides. Phenolic acids also improve cardiovascular functions, such as blood pressure and atherosclerotic lesions. This review focuses on the current knowledge of the effects of phenolic acids produced from food-derived flavonoids and amino acids by the gut microbiota on health and disease.

The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer

Abstract Introduction The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies. Objectives The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer. Methods The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters. Results A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002). Conclusion Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.

Anti-plasmodial activity of artemether-lumefantrine-tinidazole on plasmodium falciparum infected humans

Background: The emergence of multi-drug resistant strains of Plasmodium falciparum has intensified the search for effective compounds. This study aimed to evaluates the combined effects of tinidazole and artemether/lumefantrine on human participants infected with P. falciparum. Methods: The study involved 25 non-infected adults as controls and 75 infected adults, divided into three groups of 25. The groups were treated orally with 1g of Tinidazole (T) twice daily for 3 days, an 8-hourly initial dose followed by 12-hourly 80mg/480mg doses of Artemether/Lumefantrine (AL) for 3 days, and a combination of 1g tinidazole and artemether/lumefantrine (80mg/480mg) for 3 days. Venous blood samples were taken on days 0, 4, and 14 to evaluate renal function, parasitemia, hematological parameters, lipid profiles, and antioxidant measures (catalase, SOD, glutathione peroxidase, and malondialdehyde). Results: The percentage recovery with AL, T, and the combination of T and AL was 88%, 92%, and 100%, respectively. Malaria patients exhibited significantly lower levels of red blood cells, hemoglobin, packed cell volume, low-density lipoprotein, high-density lipoprotein, total cholesterol, catalase, superoxide dismutase, and glutathione peroxidase, and higher levels of white blood cells, triglycerides, and malondialdehyde compared to the control group. Post-treatment, there was a modest reversal on day 4 and a significant return to normal ranges by day 14. Malaria infection did not affect urea or creatinine levels. Conclusions: Tinidazole shows potential as a treatment for P. falciparum, with enhanced efficacy when combined with artemether/lumefantrine.

Relationship with Nut Consumption for Breakfast and Postprandial Glucose, Insulin, Triglyceride Responses: A Preliminary Study from Türkiye.

This study aimed to determine the effect of adding nuts to a regular breakfast on blood glucose, insulin, and triglyceride levels, and to evaluate participants' opinions by sex as a preliminary study for future studies. Data and biochemical parameters were collected through face-to-face interviews with Acibadem Hospital employees (n = 12) between April and September 2023. Participants consumed 30 g of nut-supplemented breakfasts for 4 weeks while maintaining their regular lifestyle. Blood tests and visual analog scale (VAS) parameters were assessed on intervention days. VAS scores indicated differences in meal taste, post-breakfast well-being, satiety, and meal adequacy, and for "feeling better after breakfast", and "providing better satiety", were significantly higher for the nut-supplemented breakfasts (p < 0.05), especially walnut-supplemented. Under the control of age, sex, and BMI variables in the participants, women responded better to peanut butter consumption than men in terms of blood insulin and triglyceride regulation (p < 0.05). However, triglyceride regulation in men was better managed by walnut consumption than in women. Understanding how nut-supplemented breakfasts impact blood glucose, insulin, and triglyceride levels, as well as consumer perceptions, is crucial for promoting healthier dietary choices.

Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice.

The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi's protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.

Nanoparticles Fueled by Enzyme for the Treatment of Hyperlipidemic Acute Pancreatitis.

Hyperlipidemic acute pancreatitis (HAP) is a serious inflammatory pancreatic disease commonly seen in patients with disorders of lipid metabolism. Decreasing blood triglyceride levels and proinflammatory factors can alleviate hyperlipidemic pancreatitis. The lipase that enhanced the Brownian motion of mesoporous silica in triglyceride solutions could accelerate decomposition of the lipid and improve the efficiency of absorption. In this study, we developed a mesoporous silica nanoparticle with dual modification of IL-6 aptamer and lipase for the treatment of HAP. The nanoparticle could increase the ability of particles to absorb inflammatory factor IL-6 and decompose triglycerides. For every 10 mg of the dual-modified nanoparticles, the efficiency of capturing IL-6 was approximately 9.67 pg/mL and of decomposing triglycerides was approximately 3.88 mg/mL in the plasma of HAP patients within 2 h. In summary, the mesoporous silica nanoparticle could absorb the IL-6 inflammatory factor through IL-6 aptamers and decompose triglycerides through lipase. Furthermore, based on clinically available plasma exchange technology, combined with our developed dual-modified nanoparticles, we designed an absorption device for the treatment of hyperlipidemic pancreatitis; it works to promote the treatment of hyperlipidemic pancreatitis.

Hypomagnesaemia and Relationship Lipid Profile in Type 2 Diabetes Patients at Janzur Hospital in Libya.

Type 2 diabetes mellitus (T2DM) is associated with increased morbidity and mortality due to the development of complications, especially due to poor glycemic control. Magnesium (Mg) is a crucial element in human health, and its deficiency plays a critical role in the development of lipid abnormalities and the initiation of diabetic complications. The study aimed to evaluate the correlation of hypomagnesemia (Mg) with the alteration of lipid profile patterns and investigate the adverse effects of glycemic control and body mass index (BMI) on magnesium levels among patients with T2DM. A total of 163 subjects whose ages ranged between 35-60 years for both sexes (males and females) were included in this study: 90 type II diabetic patients (40 males and 50 females) and 73 healthy individuals (34 males and 39 females) in Tripoli region, Western Libya. Blood glucose, HbA1c, Magnesium, and lipid profile parameters were biochemically estimated in the study along with the measurement of BMI. All the results were statistically analyzed using SPSS version 25 for applying one-way ANOVA and Person's correlation coefficient tests. The study revealed a significant decrease in serum magnesium levels (1.59 ± 0.47 mg/dL) in T2DM patients compared to the control group (2.21 ± 0.70 mg/dL) (p &lt; 0.01). Significantly elevated levels of blood glucose (140.6 ± 30.95 mg/dL vs. 89.80 ± 12.62 mg/dL, p &lt; 0.01), HbA1c (7.27 ± 2.62% vs. 5.32 ± 0.65%, p &lt; 0.01), cholesterol, triglycerides and LDL cholesterol also observed in T2DM patients compared to healthy individuals. Conversely, HDL cholesterol levels were significantly lower in the T2DM group than in controls (24.44 ± 8.88 mg/dL vs. 47.06 ± 8.75 mg/dL, p &lt; 0.01). There is a relationship between hypomagnesemia, glycemic control, and changed lipid profile in T2DM patients. Further, our results revealed a strong relationship between increased BMI and unfavorable alterations in all biochemical parameters examined.

Development, validation, and visualization of a web-based nomogram for predicting chronic kidney disease incidence at health examination centers

Purpose To develop and validate a web-based nomogram for predicting new incident chronic kidney disease (CKD) within 4 years in a cohort undergoing routine physical examination from two health examination centers. Methods One center was utilized for training and internal validation of a nomogram model involving 6515 patients, while a separate center was employed for external validation with 3152 patients. Sixteen candidate predictors, including patient demographics, medical histories, physical examination, and laboratory test data, were included in this study to ascertain factors linked to new incident CKD. A nomogram was created to predict CKD risks using a logistic model. The nomogram’s performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis. Results Out of the 9667 healthy individuals included in the study with mean age of 46 years, sex ratio (male/female) of 1.69 (6075/3592), 118 (2.59%), 51 (2.61%), and 60 (1.90%) individuals developed CKD in the training (n = 4563), internal validation (n = 1952), and external validation (n = 3152) datasets, respectively. Age, history of diabetes mellitus, systolic blood pressure, serum creatinine, albumin, and triglyceride levels were used to build the nomogram, which yielded excellent discrimination ability (training cohort, AUC = 0.8806, 95% confidence interval [CI] 0.8472–0.9141; internal validation cohort, AUC = 0.8506, 95% CI 0.7856–0.9156; external validation cohort, AUC = 0.9183, 95% CI 0.8698–0.9669). We further developed a web-based calculator for convenient application (https://luochuxuan.shinyapps.io/dynnomapp/). Conclusion Our web-based nomogram accurately predicted CKD risks in Chinese health individuals and can be easily used in clinical settings.

Evaluation of Comparative Efficacy of Kutaki (Picrorhiza kurroa Royle ex. Benth) versus Atorvastatin in the Management of Dyslipidemia - A Randomised Controlled Trial

Introduction: Dyslipidemia is a lipoprotein metabolism condition marked by elevated blood levels of triglycerides, total cholesterol, and low-density lipoprotein (LDL) cholesterol as well as decreased levels of high-density lipoprotein (HDL) cholesterol. It can be correlated with (Medoroga) Medodushti Aim and objectives: To evaluate comparative effectiveness of Kutaki (Picrorhiza kurroa Royle ex. Benth) and Atorvastatin in the management of Dyslipidemia. Methodology: Total 160 patients were randomly divided into two equal groups. Patients in Study Group A were treated with Kutaki Vati and patients in Control Group B were treated with Atorvastatin for 60 days. Data was collected by assessment of Objective parameters like body weight, BMI, lipid levels (TCH-Total serum cholesterol , HDL-High-density lipoproteins, LDL-Low-density lipoproteins, TG- Serum Triglycerides, VLDL-Serum Very Low-density lipoproteins, AST, ALT, S.Urea, S.Creatinine, Fasting blood sugar on the day 0, 30 and 60. The analysis was done with the help of inferential and descriptive statistics. Observation and Result-Kutaki and Atorvastatin both showed significant improvement in lipid levels but Kutaki showed reduction in body weight and BMI with correction in deranged Agni and bowel habit( constipation) which was not seen in Atorvastatin group. Kutaki showed no rise in AST, ALT, S Creatinin and S.urea indicating its hepatoprotective and nephroprotective properties. Conclusion-Both groups are equally effective in the management of Dyslipidemia (Medoroga).But Kutaki is effective in reducing bodyweight and BMI and safe as it showed no rise in AST, ALT, S Creatinin and S.urea.

8599 Development of an androgen receptor transgenic mouse that displays the complete attributes of Metabolic Syndrome

Abstract Disclosure: C. Alvarado: None. L.K. Beitel: None. M. Paliouras: None. M.A. Trifiro: None. The mouse androgen receptor (AR) shares over 90% homology with the human ortholog, but it lacks the CAG encoded poly-Q tract; instead, it contains a mixed glutamine/histidine tract. To study AR functionality in a more structured fashion, we created a knock-in mouse model that has only the equivalent of human poly-Q tract while maintaining the remaining mouse receptor sequence intact. Our humanized androgen receptor mouse (AR-19Q) displays a phenotype that is best described as Metabolic Syndrome (MetS). The mice gain excess weight, have hypertension, hyperglycemia, pancreatic islet cell abnormalities, and progressive non-alcoholic fatty liver disease (NAFLD). Features of MetS begin at approximately 4 months and progress till 12-14 months. Obesity: AR-19Q mice are significantly heavier, with a 35% gain of weight vs C57BL/6 mice. However, these mice are not hyperphagic at any time and eat identical quantities of chow. To assess obesity status, and found AR-19Q mice to have a significantly higher depositions of total white adipose visceral, lingual and subcutaneous vs age-matched controls. NAFLD: The progression of NAFLD is observed in AR-19Q mice. AR-19Q Histological analysis and immunohistochemistry reveal microvesicular steatosis, superseded by macrovesicular steatosis with hepatocyte balloon degeneration, scattered lobular inflammation (macrophages and lymphocytes) (6-9 months) and further superseded by perisinusoidal fibrosis (12 months). Biochemical blood analysis confirms. that there is a significant increase in alanine aminotransferase (ALT) levels, indicative of liver damage. With time classical NASH hepatitis and subsequent NASH fibrosis ensues; with several mice developing hepatocellular carcinoma (overall 20% of mice). Gene expression profiling AR-19Q mice for fatty liver genes, we observe an upregulation of inflammation genes Il-6, Il-10 and Tnf. In addition, increased Lpl (lipoprotein lipase) is indicative of increased blood triglyceride levels. On the other hand, down-regulation of G6pc (glucose-6-phosphatase) could be linked to glycogen storage disease. Down-regulation of Slc2a2 and Slc2a4, that encode GLUT2 and GLUT4, should have an influence on glucose levels, glucose homeostasis and insulin sensitivity, as insulin promotes glucose uptake through GLUT4. Type 2 Diabetes: Glucose intolerance is observed by 3-4 months followed by fasting hyperglycemia. Pancreases show advanced islet hyperplasia, concurrent with insulin resistance and type 2 diabetes. Pancreases of middle-age AR-19Q mice present with a significant islet hyperplasia, suggesting peripheral insulin resistance. We propose the use of the AR-19Q mice as a model to study the metabolic dysfunction/ deficiency leading to the MetS. The model will allow us to a better understanding into the mechanisms responsible for T2D and NAFLD-related disorders. Presentation: 6/2/2024

9285 Development of an androgen receptor transgenic mouse that displays the complete attributes of Metabolic Syndrome

Abstract Disclosure: C. Alvarado: None. L.K. Beitel: None. M. Paliouras: None. M.A. Trifiro: None. The mouse androgen receptor (AR) shares over 90% homology with the human ortholog, but it lacks the CAG encoded poly-Q tract; instead, it contains a mixed glutamine/histidine tract. To study AR functionality in a more structured fashion, we created a knock-in mouse model that has only the equivalent of human poly-Q tract while maintaining the remaining mouse receptor sequence intact. Our humanized androgen receptor mouse (AR-19Q) displays a phenotype that is best described as Metabolic Syndrome (MetS). The mice gain excess weight, have hypertension, hyperglycemia, pancreatic islet cell abnormalities, and progressive non-alcoholic fatty liver disease (NAFLD). Features of MetS begin at approximately 4 months and progress till 12-14 months. Obesity: AR-19Q mice are significantly heavier, with a 35% gain of weight vs C57BL/6 mice. However, these mice are not hyperphagic at any time and eat identical quantities of chow. To assess obesity status, and found AR-19Q mice to have a significantly higher depositions of total white adipose visceral, lingual and subcutaneous vs age-matched controls. NAFLD: The progression of NAFLD is observed in AR-19Q mice. AR-19Q Histological analysis and immunohistochemistry reveal microvesicular steatosis, superseded by macrovesicular steatosis with hepatocyte balloon degeneration, scattered lobular inflammation (macrophages and lymphocytes) (6-9 months) and further superseded by perisinusoidal fibrosis (12 months). Biochemical blood analysis confirms. that there is a significant increase in alanine aminotransferase (ALT) levels, indicative of liver damage. With time classical NASH hepatitis and subsequent NASH fibrosis ensues; with several mice developing hepatocellular carcinoma (overall 20% of mice). Gene expression profiling AR-19Q mice for fatty liver genes, we observe an upregulation of inflammation genes Il-6, Il-10 and Tnf. In addition, increased Lpl (lipoprotein lipase) is indicative of increased blood triglyceride levels. On the other hand, down-regulation of G6pc (glucose-6-phosphatase) could be linked to glycogen storage disease. Down-regulation of Slc2a2 and Slc2a4, that encode GLUT2 and GLUT4, should have an influence on glucose levels, glucose homeostasis and insulin sensitivity, as insulin promotes glucose uptake through GLUT4. Type 2 Diabetes: Glucose intolerance is observed by 3-4 months followed by fasting hyperglycemia. Pancreases show advanced islet hyperplasia, concurrent with insulin resistance and type 2 diabetes. Pancreases of middle-age AR-19Q mice present with a significant islet hyperplasia, suggesting peripheral insulin resistance. We propose the use of the AR-19Q mice as a model to study the metabolic dysfunction/ deficiency leading to the MetS. The model will allow us to a better understanding into the mechanisms responsible for T2D and NAFLD-related disorders. Presentation: 6/2/2024

Effect of Mediterranean Diet Composition on Metabolic Syndrome Marker Parameters Based on NCEP-ATP III Criteria

Metabolic syndrome refers to a cluster of metabolic abnormalities in the body, including central obesity, elevated blood pressure, high glucose, and triglyceride levels, as well as low HDL levels. The Mediterranean diet, known for its specific composition, is believed to mitigate metabolic syndrome. This study aims to assess the impact of adhering to the Mediterranean diet on individuals with metabolic syndrome. It employs an observational analytic approach, utilizing a prospective cohort of 30 participants who followed the Mediterranean diet regimen as part of their treatment at a clinic in Bandung City. Systematic Random Sampling was used to select participants, and blood pressure was measured at the beginning (T1) and end (T2) of the study. Data on dietary intake were collected using the Relative Mediterranean Diet (rMED) scale via a Food Frequency Questionnaire (FFQ). Statistical analyses, including ANOVA and Tukey’s post-hoc test, were conducted to compare dietary compositions across adherence groups and to assess the impact of the Mediterranean diet on metabolic syndrome components. The findings revealed that participants, with an average age of 57.94 years and 69.44% female, experienced significant improvements in certain metabolic syndrome components, such as waist circumference (fruit and nut intake), triglycerides (vegetable intake), HDL (meat intake), and blood glucose (dairy product intake). However, no significant effects were observed for legumes, seeds, fish, and olive oil components on MetS. Keywords: components, Mediterranean diet, MetS, NCEP-ATP III

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.

Correlation between prognosis and peripheral blood levels of NLRP3 and triglyceride-glucose index after myocardial ischemia-reperfusion injury

ObjectiveWe aim to investigate the association between prognosis and outcomes following myocardial ischemia-reperfusion injury, as well as peripheral blood levels of NLRP3 and the triglyceride-glucose index (TyG).MethodsA total of 100 patients who underwent emergency coronary intervention following myocardial infarction confirmed by coronary angiography at our hospital between October 2021 and May 2023 were included in this study. Patients were stratified into two groups based on their prognoses: the control group (n = 73), which did not experience new myocardial infarctions or require hospitalization for heart failure or suffer sudden cardiac death post-interventional treatment; and the observation group (n = 27), which experienced one or more cardiovascular events post-treatment. Patient demographics were obtained from clinical records while biochemical analyses assessed peripheral blood triglycerides, blood glucose levels, and TyG index. Additionally, ELISA measurements determined levels of NLRP3 as well as inflammatory factors IL-6, TNF-α, and CRP in peripheral blood samples. Cardiac function was evaluated according to NYHA standards. Univariable Cox regression analysis identified factors influencing patient prognosis while Pearson correlation analysis examined relationships among prognosis, outcomes following myocardial ischemia-reperfusion injury, TyG index, and peripheral blood NLRP3.ResultsNo significant differences were observed in the general characteristics between the two patient groups (P > 0.05). However, the observation group exhibited higher levels of peripheral blood triglycerides, blood glucose, and TyG index compared to the control group (P < 0.05). Additionally, levels of NLRP3 and inflammatory factors IL-6, TNF-α, and CRP were elevated in the observation group compared to the control group (P < 0.05). Cardiac function impairment was more pronounced in the observation group (P < 0.05). Notably, TyG index and peripheral blood NLRP3 demonstrated higher risk ratios compared to other biomarkers (P < 0.05), indicating their significance in prognosis and outcomes. Elevated levels of NLRP3 and TyG index were associated with poorer recovery of cardiac function, increased rehospitalization rates, and higher mortality (P < 0.05).ConclusionElevated NLRP3 levels and an increased TyG index are strongly associated with impaired cardiac function and heightened risk of cardiovascular events. These findings suggest that these biomarkers may serve as crucial prognostic indicators following myocardial ischemia-reperfusion injury.