Reduced Triglyceride Levels Research Articles

Isolation and stereospecific synthesis of indole alkaloids with lipid-lowering effects from the marine-derived fungus Colletotrichum gloeosporioides BB4

Seven undescribed compounds, colletotrichindoles A–E, colletotrichaniline A, and colletotrichdiol A, as well as three known compounds, (−)-isoalternatine A, (+)-alternatine A and 3-hydroxybutan-2-yl 2-phenylacetate were isolated from the marine-derived fungus Colletotrichu gloeosporioides BB4. The racemic mixtures colletotrichindole A，colletotrichindole C, and colletotrichdiol A were further separated by chiral chromatography to give three pairs of enantiomers (10S,11R,13S)/(10R,11S,13R)-colletotrichindole A, (10R,11R,13S)/(10S,11S,13R)-colletotrichindole C, and (9S,10S)/(9R,10R)-colletotrichdiol A, respectively. The chemical structures of seven undescribed compounds and the known compounds, (−)-isoalternatine A, and (+)-alternatine A were determined using a combination of NMR, MS, X-ray diffraction, ECD calculations, and/or chemical synthesis. All possible enantiomers of colletotrichindoles A–E were synthesized and used to determine the absolute configurations of the natural products by comparing their spectroscopic data and HPLC retention times on a chiral column. In addition, the X-ray crystal structures of the known compounds (−)-isoalternatine A and (+)-alternatine A were also obtained to confirm their absolute configurations. (10S,11R,13S)-Colletotrichindole A, colletotrichindole B, and (+)-alternatine A significantly reduced triglyceride levels in 3T3-L1 cells with EC50 values of 5.8, 9.0, and 1.3 μM, respectively.

Increased BAT Thermogenesis in Male Mouse Apolipoprotein A4 Transgenic Mice.

Dietary lipids induce apolipoprotein A4 (APOA4) production and brown adipose tissue (BAT) thermogenesis. Administration of exogenous APOA4 elevates BAT thermogenesis in chow-fed mice, but not high-fat diet (HFD)-fed mice. Chronic feeding of HFD attenuates plasma APOA4 production and BAT thermogenesis in wildtype (WT) mice. In light of these observations, we sought to determine whether steady production of APOA4 could keep BAT thermogenesis elevated, even in the presence of HFD consumption, with an aim toward eventual reduction of body weight, fat mass and plasma lipid levels. Transgenic mice with overexpression of mouse APOA4 in the small intestine (APOA4-Tg mice) produce greater plasma APOA4 than their WT controls, even when fed an atherogenic diet. Thus, we used these mice to investigate the correlation of levels of APOA4 and BAT thermogenesis during HFD consumption. The hypothesis of this study was that overexpression of mouse APOA4 in the small intestine and increased plasma APOA4 production would increase BAT thermogenesis and consequently reduce fat mass and plasma lipids of HFD-fed obese mice. To test this hypothesis, BAT thermogenic proteins, body weight, fat mass, caloric intake, and plasma lipids in male APOA4-Tg mice and WT mice fed either a chow diet or a HFD were measured. When fed a chow diet, APOA4 levels were elevated, plasma triglyceride (TG) levels were reduced, and BAT levels of UCP1 trended upward, while body weight, fat mass, caloric intake, and plasma lipids were comparable between APOA4-Tg and WT mice. After a four-week feeding of HFD, APOA4-Tg mice maintained elevated plasma APOA4 and reduced plasma TG, but UCP1 levels in BAT were significantly elevated in comparison to WT controls; body weight, fat mass and caloric intake were still comparable. After 10-week consumption of HFD, however, while APOA4-Tg mice still exhibited increased plasma APOA4, UCP1 levels and reduced TG levels, a reduction in body weight, fat mass and levels of plasma lipids and leptin were finally observed in comparison to their WT controls and independent of caloric intake. Additionally, APOA4-Tg mice exhibited increased energy expenditure at several time points when measured during the 10-week HFD feeding. Thus, overexpression of APOA4 in the small intestine and maintenance of elevated levels of plasma APOA4 appear to correlate with elevation of UCP1-dependent BAT thermogenesis and subsequent protection against HFD-induced obesity in mice.

THE EFFECT OF DIET SHOF (SIXTEEN HOUR OF FASTING) ON TRIGLYCERIDE LEVELS IN OVERWEIGHT ADOLESCENTS

Body weight exceeding normal body weight (Overweight) is a cause of increased triglyceride levels. High triglyceride levels (hypertriglyceridemia) are a risk for coronary heart disease and diabetes mellitus. Efforts that can be made to reduce hypertriglyceridemia is to reduce the number of meals with the shof diet (sixteen hours of fasting). During fasting triglycerides will be mobilized to produce energy or synthesized into glucose. The aim of this study was to determine the effect of the shof diet on reducing triglyceride levels in overweight adolescents. The research design used the Pre-Experiment One Group Pretest-Postest Design with a population of all female students of the Faculty of Health Sciences who experienced overwight as much as 25. The number of samples was 20 with a sampling technique using purposive sampling. The research instrument uses an observation sheet. Data were analyzed using the Wilcoxon test with a P value ≤ α (α = 0.05). The results showed that the value of P = 0.646, which means that there was no effect of the shof diet on reducing triglyceride levels. However, in terms of quantity, there was a decrease in triglyceride levels in most of the respondents. The shof diet can reduce triglyceride levels by controlling food consumption during the fasting window.

Efficacy and adverse effects of insulin versus plasmapheresis in patients with hypertriglyceridemia-3-induced acute pancreatitis: a systematic review and meta-analysis.

Hypertriglyceridemia is a common cause of acute pancreatitis (AP). This literature review compared the effectiveness and adverse events of insulin therapy, with or without heparin, and plasmapheresis, in reducing triglyceride levels in patients with hypertriglyceridemia-induced AP. Systematic reviews, meta-analyses, evidence syntheses, editorials, commentaries, protocols, abstracts, theses and preprints were excluded. Review Manager was used to conduct the meta-analysis. The literature search yielded 2765 articles, but only 5 were included in the systematic review and meta-analysis and the total number of participants in the review was 269. From this study's analysis, insulin ± heparin was more successful in reducing triglyceride levels than plasmapheresis (standardized mean difference -0.37, 95% confidence interval [CI] 0.99 to 0.25; P=0.25). Insulin ± heparin therapy had a lower mortality rate than plasmapheresis (risk ratio [RR] 0.70, 95%CI 0.25-1.95). Hypotension, hypoglycemia, and acute renal failure were less common in the plasmapheresis therapy group than in insulin ± heparin therapy (RR 1.13, 95%CI 0.46-2.81, RR 3.90, 95%CI 0.45-33.78, and RR 0.48, 95%CI 0.02-13.98 for hypotension, hypoglycemia, and acute renal failure, respectively). This study found no significant difference in mortality between insulin ± heparin therapy and plasmapheresis used for the reduction in triglyceride levels. It is notable that no substantial differences were observed in the most common side-effects encountered during these therapies, thus indicating non-inferiority.

Synthesis of microwave-assisted carboxamides in Triton WR-1339-induced hyperlipidemic rats: possible hypolipidemic heterocyclic compounds.

The hypolipidemic effect of furan carboxamide derivatives was investigated using the Triton WR-1339 rat model. Nineteen compounds were synthesized, including furan-2-carboxamides of benzophenones and acetophenones (a(1-4)), anilines and amine derivatives (a(5-9)), picolinic-2-carboxamide derivatives of benzophenones and acetophenone (a(10-12)) and furan-2-carboxylate esters of benzophenones and acetophenones, substituted phenols and alcohols (b(1-7)). All the necessary steps were taken to synthesize, purify, and characterize these compounds. They were synthesized by reacting acyl chlorides of the heterocycles with their corresponding amines in the presence of pyridine and tert-butyl acetate. While the conventional heating method yielded acceptable yields for some of the reactions under reflux, the microwave synthesis reactor achieved significantly higher yields for others. Rats with hyperlipidemia were induced with Triton WR-1339 and then subjected to in vivo testing via an intraperitoneal injection of 200 mg kg-1 Triton WR-1339. The model was tested using an oral dose of bezafibrate (100 mg kg-1). After 7 hours of treatment with Triton, the new derivatives represented by compounds a(1-2), a(4-5), a7, and a(10-12) showed significant activity against the complete lipid profile, including a decrease in triglyceride, total cholesterol, and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol plasma levels. At 20 mg kg-1 dose, these compounds were superior to other lipid-lowering agents in reducing triglyceride levels and slightly increased high-density lipoprotein cholesterol levels. These results indicate a mutual mechanism of action of novel compounds with fibrates, where they have a marked effect on triglyceride and high-density lipoprotein cholesterol levels; for example, a5 causes a significant reduction (p 0.0001) of triglyceride levels by 86%, and a remarkable increase (p 0.0001) in high-density lipoprotein cholesterol plasma levels by 65% as compared to hyperlipidemic rats.

The Role of Gynostemma pentaphyllum in Regulating Hyperlipidemia.

Developing effective and safe lipid-lowering drugs is highly urgent. This study aims to investigate the effectiveness and underlying mechanisms of Gynostemma pentaphyllum (GP) in the treatment of hyperlipidemia. First, a meta-analysis was performed to determine the lipid-lowering effects of GP. Thereafter, hyperlipidemia was induced in mice using a high-fat diet (HFD) and was subsequently treated with Gynostemma pentaphyllum extract (GPE) by daily gavage for 12 weeks. The body weight, tissue weight, blood lipid level, and liver lipid level were determined. Additionally, mouse serum samples were subjected to metabolomic profiling and feces were collected at different time points for metagenomic analysis via 16S rDNA sequencing. A total of 15 out of 1520 studies were retrieved from six databases. The pooled results of the meta-analysis showed that GP effectively reduced triglyceride levels and increased high-density lipoprotein cholesterol (both [Formula: see text]). Animal experiments revealed that GPE administration significantly reduced body weight, ameliorated high blood lipid levels, limited lipid deposition, and improved insulin resistance. Furthermore, GPE treatment markedly changed the intestinal microbiota structure and constitution of tryptophan metabolites. In conclusion, our results confirm the lipid-lowering effect of GP, which may be partly attributable to regulation of the intestinal microbiota and tryptophan metabolism.

Safety and efficacy of oil palm phenolic supplementation in improving lipid profile among hyperlipidemic adults: a phase 2, randomized, double-blind, placebo-controlled clinical trial.

Introduction: Oil palm phenolic (OPP) is an antioxidant aqueous palm oil by-product and contains a high amount of phenolics. OPP has been proven to have many therapeutical benefits, and one of them is as an antihyperlipidemic agent. The previous phase 1 clinical trial proved OPP was safe to be orally consumed by healthy volunteers and yielded a good lipid profile. Thus, this phase 2 clinical trial was conducted to determine the effectiveness of OPP in improving the lipid profile among hyperlipidemic subjects. Methods: A parallel, placebo-controlled, randomized, double-blinded clinical trial was conducted for 2months on 50 hyperlipidemic subjects aged 20-50years old. The subjects were randomly distributed to two treatment arms with 25 participants each: control/placebo (11 males and 14 females) and 250mg of OPP (10 males and 15 females). The subjects were required to consume one capsule per day for 60days. Fasting blood sampling for routine blood profile (hematology, liver function, renal function, and lipid) analysis and a medical examination were conducted at baseline, day 30, and day 60. t-test analysis was used to compare the difference between two test groups. Results: The baseline lipid profile between control group (TC, 5.78 ± 0.52mmol/L; LDL, 3.88 ± 0.51mmol/L; HDL, 1.30 ± 0.25; TG, 1.30 ± 0.82), and 250mg OPP (TC, 5.76 ± 0.54mmol/L; LDL, 3.82 ± 0.59mmol/L; HDL, 1.37 ± 0.34; TG, 1.25 ± 0.54) is insignificant. No serious adverse events (SAEs) were reported. No abnormality in fasting blood parameters in all groups was found. Compared to the control group among male participants, the 250mg OPP group showed an improved serum triglyceride level. There were no statistically significant changes in all blood parameters from day 1 to day 60 with the exception of triglyceride level. Conclusion: The absence of SAEs reported and no abnormal findings in biochemistry and hematology results suggested that the 250mg OPP was safe to be taken by hyperlipidemic patients with a high probability of reducing triglyceride level in hyperlipidemic male patients The outcomes from this phase II trial suggest that by incorporating OPP supplements into the diet may be a promising strategy for individuals with hyperlipidemia to improve their lipid profiles and reduce cardiovascular risk. However, more research is needed to fully understand the mechanisms of action and establish the long-term efficacy and safety of OPP supplementation in larger scale. Limitation: Small samples size hence lack of diversity (25 subjects per groups) and early sharing of treatment-response results. Clinical Trial Registration: clinicaltrials.gov, identifier NCT04573218.

Acute pancreatitis due to hypertriglyceridemia: Plasmapheresis versus medical treatment

OBJECTIVE: Hypertriglyceridemia (HTG) is the third-most common cause of acute pancreatitis. Plasmapheresis is an extracorporeal treatment method used for treatment. This study aimed to investigate the efficacy of medical treatment and plasmapheresis in patients with acute pancreatitis due to HTG. METHODS: This was a retrospective cross-sectional study. The patients were divided into two groups according to the treatment they received as those who received only medical treatment and those who performed plasmapheresis with medical treatment. According to the treatment received by the patients; clinical, demographic, and laboratory data, Ranson scores, and bedside index of severity in acute pancreatitis (BISAP) scores, decrease in triglyceride levels in 24 h, length of hospital stay, and outcomes were recorded. RESULTS: Forty-seven patients were included in the study. The level of triglyceride decreases at the 24th h was 59.7% ±17.3% in those who received medical treatment and was 70.4% ±15.1% in those who received plasmapheresis (P = 0.032). Receiver operating characteristic curve analysis was performed to predict the need for plasmapheresis treatment, area under the curve (AUC) value of the triglyceride level was the highest (AUC: 0.822, 95% confidence interval: [0.703–0.940]; P < 0.001), the sensitivity and specificity were 83.3% and 72.4%, respectively, and the cut-off value of triglyceride was accepted as 3079.5 mg/dL. CONCLUSION: Plasma triglyceride levels and BISAP score on admission may help physicians to predict the need for plasmapheresis. Plasmapheresis helps to rapidly reduce triglyceride levels in patients with HTG-associated acute pancreatitis.

Berberine alleviates non-alcoholic hepatic steatosis partially by promoting SIRT1 deacetylation of CPT1A in mice.

Berberine effectively alleviates non-alcoholic fatty liver disease (NAFLD). Nevertheless, the mechanism is incompletely comprehended. It has been reported that SIRT1 mediates lipid metabolism in liver and berberine promotes the expression of SIRT1 in hepatocytes. We hypothesized that SIRT1 mediated the effect of berberine on NAFLD. The effects of berberine on NAFLD were evaluated in C57BL/6J mice fed a high-fat diet (HFD) and in mouse primary hepatocytes and cell lines exposed to palmitate. The change of fatty acid oxidation (FAO) and the activity of CPT1A were observed in HepG2 cells. Quantitative real-time polymerase chain reaction and Western blot were employed to observe the expression of SIRT1 and lipid metabolism-related molecules. The interaction between SIRT1 and CPT1A was investigated by using co-immunoprecipitation assay in HEK293T cells. Berberine treatment attenuated hepatic steatosis, reduced triglyceride (190.1 ± 11.2 μmol/g liver vs 113.6 ± 7.6 μmol/g liver, P < 0.001) and cholesterol (11.3 ± 2.5 μmol/g liver vs 6.3 ± 0.4 μmol/g liver, P < 0.001) concentration in the liver, and improved lipid and glucose metabolism disorders compared with the HFD group. The expression of SIRT1 was reduced in the liver of NAFLD patients and mouse models. Berberine increased the expression of SIRT1 and promoted the protein level of CPT1A and its activity in HepG2 cells. SIRT1 overexpression mimicked the effect of berberine on reducing triglyceride levels in HepG2 cells, whereas SIRT1 knock-down attenuated the effect of berberine. Mechanistically, berberine increased the expression of SIRT1. SIRT1 deacetylated CPT1A at the Lys675 site, which suppressed its ubiquitin-dependent degradation, thereby promoting FAO and alleviating non-alcoholic liver steatosis. Berberine promoted SIRT1 deacetylation of CPT1A at the Lys675 site, which reduced the ubiquitin-dependent degradation of CPT1A and ameliorated non-alcoholic liver steatosis.

Emphasis on Icosapent Ethyl for Cardiovascular Risk Reduction: A Systematic Review.

Despite the widespread use of lipid-lowering agents such as statins, cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Icosapent ethyl (IPE) (Vascepa), an ethyl ester of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA), has gained widespread popularity as an adjunctive agent that targets multiple and additional mechanisms linked to the incidence of cardiovascular (CV) events and the causative pathway of atherosclerosis. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 standards were used to conduct this systematic review. In this review, we assessed various studies from PubMed, PubMed Central (PMC), and Google Scholar to evaluate the mechanisms of action and beneficial effects of IPEin the reduction ofCVDoutcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) has demonstrated a significant reduction in CV mortality with 4 g/day IPE as compared to placebo. All other trials and observational studies have supported the role of Vascepa in hypertriglyceridemia and CV risk reduction. In conclusion, the use of IPE has been shown to significantly reduce triglyceride levels and reduce CV risks in patients receiving optimal statin therapy.

The Effect of Edamame milk on Triglyceride Levels in Diabetes Wistar Rats

Type 2 diabetes is a hyperglycemic disease caused by cell insensitivity due to increasing blood glucose levels due to reduced insulin secretion. Hyperglycemia conditions have the risk to increase triglyceride levels in type 2 diabetes. Edamame milk contained isoflavones that had potential to reduce triglyceride level. To find out the effect of given edamame milk on triglyceride levels in type 2 diabetes wistar rats. A true experimental with pre-post randomized control group design towards 24 type 2 diabetes wistar rats in 4 groups. Groups K(+), P1 and P2 were induced Streptozotocin 45 mg/kgBW and Nicotinamide 110 mg/kgBW. P1 and P2 groups were given edamame milk at a dose of 1,8 ml/200grBW and 3,6 ml/200grBW for 28 days. Blood samples were taken through a retro-orbitalis plexus. Triglyceride levels were tested pre and post intervention using the GPO-PAP method. Data analysis had used Paired T test and One Way ANOVA test with Post hoc follow-up test. Triglyceride levels in P1 and P2 groups had significant differences (p&lt;0,05) against the control groups. Edamame milk could reduce triglyceride levels of groups P1 and P2 at dose 1,8 ml/200grBW and 3,6 ml/200grBW. P2 was the highest group reduced in triglyceride levels up to 29,41±3,55 mg/dL. Edamame milk could reduced triglycerides levels in 28 days. Given an edamame milk at a dose 3,6 ml/200grBW more efficient to reduce triglyceride levels in type 2 diabestes rats significantly

Association of maternal triglyceride responses to thyroid function in early pregnancy with gestational diabetes mellitus.

The prevalence of Gestational Diabetes Mellitus (GDM) is increasing globally, and high levels of triglyceride (TG) and low levels of free thyroxine (FT4) in early pregnancy are associated with an increased risk of GDM; however, the interaction and mediation effects remain unknown. The aim of the present study is to examine the impact of FT4 and TG combined effects on the prevalence of GDM and the corresponding casual paths among women in early pregnancy. This study comprised 40,156 pregnant women for whom early pregnancy thyroid hormones, fasting blood glucose as well as triglyceride were available. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines, and the pregnant women were grouped and compared according to the results. An L-shaped association between FT4 and GDM was observed. The prevalence of GDM increased with increasing TG levels. After accounting for multiple covariables, the highest risk for GDM was found among pregnant women of lower FT4 with the highest TG concentrations (odds ratio, 2.44, 95% CI, 2.14 to 2.80; P<0.001) compared with mothers of higher FT4 with the TG levels in the lowest quartile (Q1). There was a significant interaction effect of maternal FT4 and TG levels on the risk for GDM (P for interaction = 0.036). The estimated proportion of the mediating effect of maternal TG levels was 21.3% (95% CI, 15.6% to 36.0%; P < 0.001). In the sensitivity analysis, the mediating effect of TG levels was stable across subgroups. This study demonstrated an L-shaped association between maternal FT4 levels and GDM and the benefit of low TG levels, in which maternal TG levels act as an important mediator in this association. Our findings suggested that pregnant women who treat hypothyroidism should also reduce triglycerides levels in early pregnancy to prevent GDM development.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk

BackgroundHigh triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator–activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.MethodsIn a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes.ResultsAmong 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were −26.2% for triglycerides, −25.8% for very-low-density lipoprotein (VLDL) cholesterol, −25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), −27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease.ConclusionsAmong patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.)

Abstract 13889: Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Noncalcified Coronary Plaque and Coronary Artery Calcium Score in Subjects With Coronary Artery Disease According to Hypertension Status

Introduction: Higher amounts of noncalcified plaque and higher coronary artery calcium (CAC) scores are associated with increased cardiovascular events and mortality. The effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on noncalcified coronary plaque and more advanced calcified plaque as measured by the CAC score according to hypertensive (HTN) status is unknown. Methods: A total of 242 subjects with coronary artery disease (CAD) on statin were randomized to 3.36 g of EPA+DHA or none (control) for 30 months. Coronary plaque composition and CAC scores were measured with computed tomographic coronary angiography at baseline and 30-month follow-up. Results: Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3) and median [IQR] triglyceride (TG): 117.5 mg/dL [81.3,166.8]. Despite a significantly higher CAC score at baseline in HTN subjects, both HTN and normotensive (NTN) subjects had similar CAC progression over 30 months with no difference between EPA+DHA and control groups (Figure B). NTN subjects on EPA+DHA had a 20.7% reduction in TG level and 36.6% lower neutrophil count, a marker of inflammation, and lack of progression of noncalcified plaque compared to control who had progression (median % change: -7.6 vs 13.2 mm 3 /mm, P=0.008) (Figure A). In contrast, HTN subjects on EPA+DHA and control had progression of noncalcified coronary plaque with no significant difference between the two groups (Figure A) Conclusions: EPA+DHA prevented progression of noncalcified plaque in NTN subjects but not HTN subjects with no effect on more advanced plaque which has calcified in the setting of low LDL-C and TG levels. The benefit of EPA+DHA in CAD patients on statin therapy appears limited to noncalcified coronary plaque in NTN subjects. Whether this benefit is related to more favorable effects on inflammation based on blood pressure status should be examined further.

Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway

It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid, 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting. Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas, as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor, compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.

ODP135 A New Life-Saving Treatment not yet Included in Guidelines for Recurrent Severe Hypertriglyceridemia-Induced Pancreatitis

Abstract Severe hypertriglyceridemia is a rare cause of acute pancreatitis especially in non-alcoholic, non- gallstones, non-obese, non-diabetic patients and has a few options for its management. Hypertriglyceridemia-induced pancreatitis causes 1 to 14 percent of all cases of acute pancreatitis. The risk of developing acute pancreatitis is approximately 5 percent with serum triglycerides &amp;gt;1000 mg/dL and 10 to 20 percent with triglycerides &amp;gt;2000 mg/dL. This is the case of a 63-year-old female who came to the Emergency Department with acute onset of abdominal pain, located at the mid-epigastric region, radiating to back, 10/10 in a scale of severity, no alleviating or aggravating factor, accompanied by nausea, 5 episodes of bilious emesis. Past medical history includes recurrent acute pancreatitis induced by hypertriglyceridemia (3 episodes last year), arterial hypertension, and dyslipidemia treated with Fenofibrate and Atorvastatin. Denies toxic habits. Physical examination showed abdominal tenderness with positive bowel sounds. Laboratories report cholesterol: 44mg/dl, triglycerides: 5,831mg/dl, LDL: -735 mg/dl, and HDL: 13 mg/dl. The patient condition warranted admission to the intensive care unit with the diagnosis of severe hypertriglyceridemia induced pancreatitis. Initially managed with insulin drip, bowel rest, and conservative management, which did not result in any improvement in her symptoms. A successful method of treatment relies on plasmapheresis for the lowering of triglyceride levels. This was first reported in 1978 by Betteridge and can result in a rapid decrease in triglyceride levels over a short period of time compared to the other treatment options. In this case, vascular surgery was consulted for apheresis catheter placement, with triglyceride improvement from 5,831mg/dl to 973 mg/dl after initial and single apheresis intervention, as the patient's symptoms resolved. Triglyceride levels decreased to 113 mg/dl after a week of therapy with plasmapheresis. The patient continues evaluation at the outpatient clinic and currently has been without recurrence of pancreatitis for the last year. Finally, the use of insulin infusion in conjunction with plasmapheresis has been demonstrated to be a viable option for rapid improvement in symptoms associated with acute pancreatitis associated with elevated triglycerides. Plasmapheresis rapidly removes triglycerides from the circulation removing the inciting factor, decreasing inflammation, and damage to the pancreas. The patient's triglyceride level decreased to 973 mg/dl the next day from 5,831mg/dl initially and the patient's symptoms resolved. Plasmapheresis is not an established guideline for the management of hypertriglyceridemia -induced pancreatitis. Plasmapheresis lowers the lipid levels drastically within hours compared to conservative therapy that usually takes several days to achieve the same reduction in triglycerides levels. Presentation: No date and time listed

RF34 | PMON263 Study of Testosterone Replacement in Hypogonadal Men With Uncontrolled Type 2 Diabetes – a Randomised Double Blinded Placebo Controlled Trial (STRIDE Study)

Abstract Objective This RCT set out to test the effect of testosterone on glycaemic control, parameters of metabolic control and quality of life(QoL) in a cohort of people with poorly-controlled type 2 diabetes and hypogonadism. Research design and methods: This is a randomised double-blinded placebo-controlled add-on trial of intramuscular testosterone undecanoate (Nebido®) administered every 12 weeks in 65 hypogonadal men with poorly-controlled type 2 diabetes. Phase 1 patients were randomly assigned to either treatment or placebo arm for 6 months of TRT. Phase 2 was an open-labelled phase for 6 months and patients on placebo moved on to the treatment group wherein patients in the treatment group continued. Anthropometric measurements, questionnaires and biochemical parameters were recorded at baseline and every three months for a year. Results Mean age of the cohort was 59±8.98 years(mean±SD). Mean duration since diagnosis of diabetes was 8.6 years. 17(26%) were on insulin. Baseline cohorts were comparable. There was no improvement in mean HbA1c or fasting plasma glucose(FBG) between the active and placebo groups after 6 months of TRT. No difference was found in HbA1c or FBG at 12 months compared to baseline in the active group either. Our study also showed a significant decrease in serum triglycerides (-0.497±0.213mmol/l, p=0.023) and improvement in left hand grip strength (p=0.025) at 6 months post treatment in the active group compared to placebo group. There was no significant difference in the mean weight, BMI, WC, WHR, fat mass, fat percentage or fat free mass between the groups. Our study is the first ever RCT to show a significant improvement in total AMS (aging male symptom) scores from baseline after 6 months of TU treatment compared to placebo group (p&amp;lt;0.05) in a cohort with poorly-controlled type 2 diabetes and hypogonadism. Another key finding from our study substantiating the clinical argument of treatment of patients with hypogonadism in diabetes cohort is that the proportion of patients with severe symptoms moving to a less severe category (low/mild/moderate severity) was 46% in the active vs only 28% in placebo group(p=0.0024). Conclusions Our study concludes that testosterone therapy did not have a significant improvement in glycaemic control at 6 months between the active and placebo groups and at 12 months within the in the active group and may need longer duration to see the positive effects especially in cohort of people who have had long duration of diabetes. There was a significant reduction in triglyceride levels and increase muscular strength after 6 months of TRT. STRIDE study is the first ever RCT to show a significant improvement in clinical symptoms and symptom severity following testosterone treatment in patients with hypogonadism and type 2 diabetes after 6 months of testosterone treatment. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.

Early Time-Restricted Eating Reduces Weight and Improves Glycemic Response in Young Adults: A Pre-Post Single-Arm Intervention Study

Introduction: Time-restricted eating (TRE) has cardiometabolic health benefits by optimizing circadian rhythms. However, limited data are available on the effect of early TRE in young adults. The objective of this pre-post single-arm trial was to test the effect of TRE on body composition and cardiometabolic risk factors and to evaluate changes in meal and sleep timing by TRE among young adults with typically late bedtime. Methods: This 4-week intervention was conducted in healthy young adults aged 18–39 years. Dietary records with time logs were collected before and during the intervention, and nutrient intake and meal timing were evaluated. Snack packages containing 20 g of protein per day were provided weekly. Body composition was measured weekly using bioelectrical impedance analysis. Blood samples were collected before and after the intervention, and cardiometabolic parameters were evaluated. Results: Of the 36 screened participants, 34 completed the study (completion rate 94.4%). The average age was 23.4 ± 2.9 years with 64.7% female. The mean wake-up time and bedtime were 09:16 ± 01:26 and 01:51 ± 01:39 with average sleep duration of 7.4 ± 1.4 h. Body weight and fat mass, excluding muscle mass, were significantly reduced over 4 weeks compared to baseline only in the early TRE group starting before noon. The early TRE group also showed significantly reduced fasting glucose, fasting insulin, and serum triglyceride (TG) levels after 4 weeks. However, the late TRE group starting after noon showed no significant changes except a reduced TG level. The meal timing was changed by TRE, where the first meal was delayed and the last meal was shifted. Neither sleep duration nor timing was significantly changed by TRE. Energy intakes were not different, but protein intake increased from 19.2% to 22.6% due to snack packages during intervention. However, no significant correlation between nutrient intakes and body composition changes was found. There were no adverse events related to study participation. Conclusions: An early TRE regimen may be a feasible and effective strategy to manage body composition and cardiometabolic risk factors in young adults without altering the sleep-wake cycle.

ANTIOXIDANT AND ANTIDIABETIC EFFECTS OF VERNONIA AMYGDALINA DEL. ETHANOLIC LEAF EXTRACT ON DROSOPHILA MELANOGASTER

Diabetes mellitus (DM) is a significant global public health concern. Vernonia amygdalina Del. is a medicinal herb reported to have multiple biological activities, including antidiabetic properties. This work investigated the in vitro and in vivo antioxidant and antidiabetic properties of Vernonia amygdalina Del. ethanolic leaf extract (VAE). Total phenolic content (TPC) and total flavonoid (TFC) content of VAE were assessed using Folin-Ciocalteu and aluminum chloride colorimetric methods, respectively. The antioxidant activities of VAE were assessed by the DPPH and FRAP methods. The effects of the VAE on the gustatory, toxicity, body weight, and triglycerides were determined in wild-type Drosophila melanogaster. The results showed that VAE had high levels of TPC (57.45±0.45 mg GAE/g DW), TFC 79.55±0.88 mg QE/g DW), and in vitro antioxidant activities (0.11±0.02 mg/mL).VAE exhibited the in vitro inhibitory activities against α-glucosidase and α-amylase with the IC50 values of 267.69±11.51 µg mL-1 and 331.56±26.47 µg mL-1. Treatment with VAE at 5 and 15 mg/mL did not affect the fruit fly survival, indicating that VAE was not toxic to the insects. In D. melanogaster supplemented with 15 mg/mL VAE, significant increases in survival time after exposure to H2O2 and paraquat were observed. VAE also reduced triglyceride levels in fruit flies fed with a high-sugar diet. These findings suggest that VAE, which is derived from natural sources, possesses antioxidant and antidiabetic properties and may also be used as a potential source of bioactive compounds for managing hyperglycemia.

Walking Exercise Reduces Postprandial Lipemia but Does Not Influence Postprandial Hemorheological Properties and Oxidative Stress.

A higher postprandial triglycerides response and hemorheological abnormalities may increase the incidence of metabolic disorders and negatively interfere with the aging process. A single session of preprandial endurance exercise was found to be effective in reducing triglyceride levels after a high-fat diet. However, whether the exercise-induced reduction in postprandial triglyceride levels influences hemorheological indicators remains unknown. This study aims to investigate the effects of postprandial lipemia on hemorheological properties and oxidative stress. Eight healthy young male participants completed two experimental trials. On day 1, the participants were randomly assigned to walk for 1 h at 50% VO2max (EE trial) or rest (CON trial). On day 2, participants rested and consumed a high-fat meal in the morning. Results: The postprandial area under the curve (AUC) of plasma TG concentration was significantly lower in EE compared to CON (EE: 9.2 ± 1.9; CON: 10.9 ± 1.7 mmol/L·h−1; p = 0.013; Cohen’s d = 0.036). No significant difference was observed in hemorheological properties and MDA (p > 0.05). Endurance exercise effectively decreased postprandial TG concentration but did not influence the postprandial hemorheological properties and oxidative stress indicators.