Reduced Serum Triglyceride Levels Research Articles

Hepatocyte-specific Epidermal Growth Factor Receptor Deletion Promotes Fibrosis but has no Effect on Steatosis in Fast-food Diet Model of Metabolic Dysfunction-associated Steatotic Liver Disease

MASLD has become the most prevalent chronic liver disorder, with no approved treatment. Our previous work demonstrated the efficacy of a pan-ErbB inhibitor, Canertinib, in reducing steatosis and fibrosis in a murine fast-food diet (FFD) model of MASLD. The current study explores the effects of hepatocyte-specific ErbB1 (i.e. EGFR) deletion in the FFD model. EGFRflox/flox mice, treated with AAV8-TBG-CRE to delete EGFR specifically in hepatocytes (EGFR-KO), were fed either a chow-diet or FFD for 2 or 5-months. Hepatocyte-specific EGFR deletion reduced serum triglyceride levels but did not prevent steatosis. Surprisingly, hepatic fibrosis was increased in EGFR-KO mice in the long-term study, which correlated with activation of TGFβ1/fibrosis signaling pathways. Further, nuclear levels of some of the major MASLD regulating transcription factors (SREBP1, PPARγ, PPARα, and HNF4α) were altered in FFD-fed EGFR-KO mice. Transcriptomic analysis revealed significant alteration of lipid metabolism pathways in EGFR-KO mice with changes in several relevant genes, including downregulation of fatty-acid synthase and induction of lipolysis gene, Pnpla2, without impacting overall steatosis. Interestingly, EGFR downstream signaling mediators, including AKT, remain activated in EGFR-KO mice, which correlated with increased activity pattern of other receptor tyrosine kinases, including ErbB3/MET, in transcriptomic analysis. Lastly, Canertinib treatment in EGFR-KO mice, which inhibits all ErbB receptors, successfully reduced steatosis, suggesting the compensatory roles of other ErbB receptors in supporting MASLD without EGFR. Hepatocyte-specific EGFR-KO did not impact steatosis, but enhanced fibrosis in the FFD model of MASLD. Gene-networks associated with lipid metabolism were greatly altered in EGFR-KO, but phenotypic effects might be compensated by alternate signaling-pathways.

The Probiotic Kluyveromyces lactis JSA 18 Alleviates Obesity and Hyperlipidemia in High-Fat Diet C57BL/6J Mice.

Obesity poses a significant threat to various health conditions such as heart diseases, diabetes, high blood pressure, and heart attack, with the gut microbiota playing a crucial role in maintaining the body's energy balance. We identified a novel probiotic fungal strain, Kluyveromyces lactis JSA 18 (K. lactis), which was isolated from yak milk and was found to possess anti-obesity properties. Additionally, Lactobacillus plantarum CGMCC 8198 (LP8198) from our previous study was also included to evaluate its anti-obesity properties. The findings indicated that K. lactis caused a notable reduction in weight gain, liver and fat indexes, and hyperlipidemia in mice fed a high-fat diet (HFD). Administering K. lactis and LP8198 to mice on a high-fat diet resulted in a reduction of serum triglyceride levels. Furthermore, the supplements reduced ALT and AST activity, and inhibited the production of inflammatory cytokines such as TNF-α and IL-1β. In addition, lipid metabolism was enhanced by the downregulation of ACC1, PPAR-γ, SREBP-1, and Fasn. Moreover, this study found that K. lactis and LP8198 have little effect on gut bacteria. Additionally, K. lactis partially influenced intestinal fungi, while LP8198 had a minor influence on gut mycobiota. The main goal of this research was to show how effective K. lactis can be as a probiotic in combating obesity.

Therapeutic plasma exchange decreases serum triglyceride level rapidly and reduces early recurrence rate but no advantages in improving outcomes for patients with hyperlipidemic acute pancreatitis: a retrospective propensity score matching analysis based on twenty year’s experience

BackgroundHyperlipidaemic acute pancreatitis (HLAP) has become the most common cause of acute pancreatitis (AP) not due to gallstones or alcohol (Mosztbacher et al, Pancreatology 20:608-616, 2020; Yin et al, Pancreas 46:504-509, 2017). Therapeutic plasma exchange (TPE) has been reported to be effective in reducing serum TG levels which is important in management of HLAP (World J Clin Cases 9:5794-803, 2021). However, studies on TPE are mostly focusing on cases reports, TPE remains poorly evaluated till date and need to be compared with conservative therapy with a well-designed study.MethodsA retrospectively cohort study on HLAP patients between January 2003 and July 2023 was conducted. Factors correlated with efficacy of TPE were included in a propensity model to balance the confounding factors and minimize selection bias. Patients with and without TPE were matched 1:2 based on the propensity score to generate the compared groups. Lipid profiles were detected on admission and consecutive 7 days. The triglyceride (TG) level decline rates, percentage of patients to reach the target TG levels, early recurrence rate, local complications and mortality were compared between groups.ResultsA total of 504 HLAP patients were identified. Since TPE was scarcely performed on patients with TG < 11.3 mmol/L, 152 patients with TG level 5.65 to 11.3 mmol/L were excluded while 352 with TG ≧11.3 mmol/L were enrolled. After excluding 25 cases with incomplete data or pregnancy, 327 patients, of whom 109 treated without TPE while 218 treated with TPE, were included in data analysis. One-to-two propensity-score matching generated 78 pairs, 194 patients with well-balanced baseline characteristics. Of 194 patients enrolled after matching done, 78 were treated without while 116 with TPE. In the matched cohort (n = 194), patients treated with TPE had a higher TG decline rate in 48 h than those without TPE (70.00% vs 54.00%, P = 0.001); the early recurrence rates were 8.96% vs 1.83%, p = 0.055. If only SAP patients were analyzed, the early recurrence rates were 14.81% vs 0.00% (p = 0.026) respectively. For patients with CT severity index (CTSI) rechecked within 14 days, early CTSI improment rate were 40.90% vs 31.91%. Local complications checked 6 months after discharge were 44.12% vs 38.30%. Mortality was 1.28% vs 1.72%. No differences were found in early stage CTSI improment rate (P = .589), local complications (P = .451) or motality between two groups.ConclusionsTPE reduces TG levels more quickly in 48 h compared with those with conservative treatment, but no difference in the consecutive days. TPE tends to reduce the early recurrence rate comparing with conventional therapy, but TPE has no advantages in improving CTSI in early stage, and no improvement for outcomes including local complications and mortalty.

PENGARUH PEMBERIAN EKSTRAK ETANOL DAUN TUMBUHAN AKAR KAIK-KAIK (Uncaria cordata (Lour.)Merr) TERHADAP KADAR TRIGLISERIDA SERUM TIKUS PUTIH (Rattus norvegicus) JANTAN

Hypertriglyceridemia is a condition when there is an increase in triglyceride levels in the blood. Hypertriglyceridemia can cause heart problems. One of the plants that can be used as medicine is the root plant kaik-kaik (Uncaria cordata (lour.) Merr). This study aims to determine the effect of giving ethanol extract of kaik-kaik (Uncaria cordata (lour.) Merr) leaves on serum triglyceride levels of male white rats (Rattus norvegicus). The parameters used were serum triglyceride levels of male white rats induced by high fat feed, namely quail egg yolk as much as 10 ml/kgBB. This study used 18 male white rats which were divided into 6 groups with 3 rats per group. The normal group was fed only with rats and Na CMC suspension, the negative group was given high-fat feed induction and Na CMC suspension. The positive group was given high-fat feed induction and 0.9 mg/kgBB of atorvastatin suspension. The treatment group was given high-fat feed and a suspension of ethanol extract of kaik-kaik root leaves at doses of 100, 200, and 400 mg/kgBB as much as 1% of body weight given orally. The method used was colorimetric enzymatic using a Mindray® photometer (BA-88A) at a wavelength of 510 nm. Triglyceride level data on days 0, 15, 22 and 29 were analyzed by one-way ANOVA test and repeated ANOVA. The results showed that the ethanol extract of kaik-kaik root (Uncaria cordata (Lour.) Merr) leaves at doses of 100, 200 and 400 mg/kgBB had an effect in reducing serum triglyceride levels of male white rats (Rattus norvegicus) indicated by differences. which was significant (p &lt;0.05) with negative control and showed activity to decrease triglyceride levels which was not significantly different (p&gt; 0.05) with atorvastatin.

Sertraline and Fluoxetine in Adult Patients with Comorbid Depression and Type II Diabetes Mellitus: A Randomized Controlled Trial

Background: Depressive disorders are more common in patients with diabetes mellitus (DM) compared to the general population. Objectives: Due to heterogeneous evidence on the impact of antidepressants on serum glucose profile, this study was conducted to examine the effects of sertraline and fluoxetine on serum glucose levels in patients with comorbid depression and diabetes. Methods: In this randomized controlled trial, 40 adult patients with DM and depression were randomly allocated into two groups (n = 20 per group). The first group received 50 - 200 mg/day of sertraline, and the second group received 20 - 60 mg/day of fluoxetine. The Beck Depression Inventory (BDI-II) was used to determine depression severity, and body mass index (BMI), blood pressure, serum lipid profile, fasting blood sugar (FBS), 2-hour post-prandial blood glucose, and HbA1c were measured at the baseline and 12 weeks after the intervention. Results: Body mass index (P = 0.40), systolic blood pressure (P = 0.41), FBS (P = 0.46), 2-hour post-prandial blood glucose (P = 0.53), HbA1c (P = 0.59), serum total cholesterol (P = 0.78), and LDL cholesterol (P = 0.62) insignificantly reduced in both groups after the intervention compared to the baseline; however, the reduction in serum triglyceride level was statistically significant (P = 0.04). Also, the depression severity score was reduced in both groups; however, the difference was not statistically significant (P = 0.27). Conclusions: In adult patients diagnosed with comorbid depression and type II diabetes mellitus, three months of treatment with sertraline or fluoxetine comparably mitigated depressive symptoms and reduced HbA1c, FBS, and 2-hour post-prandial blood glucose.

Efficacy of pemafibrate in patients with dyslipidemia: A systematic review and meta-analysis of randomized controlled trials

This study aimed to evaluate the efficacy of pemafibrate in patients with hypertriglyceridemia compared to a placebo or fenofibrate through a rigorous systematic review process. To achieve this, we conducted comprehensive searches in the PubMed, Cochrane Library, and Embase databases. The data extraction process was based on published reports, and the assessment of study quality adhered to the PRISMA guidelines. A random-effects model was employed to calculate mean differences (MD) and 95% confidence intervals (CI). Statistical significance was established at P &lt; 0.05, with I&amp;sup2; values exceeding 25%, denoting a significant degree of heterogeneity. The primary outcomes of interest were MDs in triglycerides (TG) and non-high-density lipoprotein (HDL) cholesterol. The review protocol was registered with PROSPERO under the identifier CRD42022374852. Nine studies involving 12,644 patients were included, with 6699 (53%) patients receiving pemafibrate. The meta-analysis revealed a significant reduction in serum TG levels in the intervention group (0.4 mg/day) compared to the placebo group (MD: &amp;minus;48.29; 95% CI: &amp;minus;61.45 &amp;ndash; &amp;minus;35.13; P &lt; 0.0001; I&amp;sup2; = 93%). Pemafibrate (0.4 mg/day) also led to significantly lower non-HDL cholesterol levels compared to control (MD: &amp;minus;6.35; 95% CI: &amp;minus;10.62 &amp;ndash; &amp;minus;2.08; P &lt; 0.0001; I&amp;sup2; = 82%). There were no significant differences in TG reduction between pemafibrate (0.2 mg/day) and fenofibrate (200 mg/day) (MD: &amp;minus;2.90; 95% CI: &amp;minus;12.90 &amp;ndash; 7.11; P = 0.003; I2 = 83%), or between pemafibrate (0.1 mg/day and 0.2 mg/day) and placebo (TG and non-HDL cholesterol levels). In conclusion, pemafibrate demonstrated efficacy in decreasing TG and non-HDL cholesterol levels for dyslipidemia patients, especially at a dosage of 0.4 mg/day compared to a placebo.

Preventive and Therapeutic Effects of Silybum marianum Seed Extract Rich in Silydianin and Silychristin in a Rat Model of Metabolic Syndrome.

Metabolic syndrome (MetS) has become an increasing global health problem, which leads to cardiovascular diseases and type 2 diabetes. Silybum marianum extracts have been reported to possess several biological activities. In this study, an ethyl acetate extract prepared from S. marianum seeds of the Iraqi Kurdistan region was analyzed to identify its chemical constituents. Subsequently, its potential for the prevention and treatment of MetS was studied in a rat model induced by a high-fat/high-fructose diet (HFD/F). Silydianin and silychristin were the most abundant flavonolignan constituents (39.4%) identified in the S. marianum extract (SMEE). HFD/F-induced rats treated with SMEE exhibited preventive effects including reduced serum triglyceride levels (TG), decreased glucose levels in an oral glucose tolerance test (p < 0.001), attenuated weight gain, and reduced blood pressure compared to the untreated control group. Therapeutic application of SMEE after inducing MetS led to lowering of TG (p < 0.001) and glucose levels, in addition to reducing weight gain and normalizing blood pressure (p < 0.005). Thus, S. marianum extract rich in silydianin and silychristin may be useful for preventing and attenuating MetS, and further research and clinical trials are warranted.

Bile acids supplementation modulates lipid metabolism, intestinal function, and cecal microbiota in geese.

Bile acids(BAs) are important components of bile and play a significant role in fat metabolism. However, there is currently no systematic evaluation of the use of BAs as feed additives for geese.This study aimed to investigate the effects of adding BAs to goose feed on growth performance, lipid metabolism, intestinal morphology, mucosal barrier function, and cecal microbiota. A total of 168 28-day-old geese were randomly assigned to four treatment groups and fed diets supplemented with 0, 75, 150, or 300 mg/kg of BAs for 28 days. The addition of 75 and 150 mg/kg of BAs significantly improved the feed/gain (F/G) (p < 0.05).The addition of BAs decreased abdominal fat percentage and serum total cholesterol (TC) levels, with 150 mg/kg of BAs significantly reducing serum triglyceride levels and increased expression of Farnesoid X Receptor (FXR) mRNA in the liver(p < 0.05), 300 mg/kg of BAs significantly increasing the expression level of liver peroxisome proliferator-activated receptor α (PPARα) (p < 0.05). In terms of intestinal morphology and mucosal barrier function, 150 mg/kg of BAs significantly increased villus height (VH) and VH/crypt depth (CD) in the jejunum (p < 0.05). The addition of 150 and 300 mg/kg of BAs significantly reduced the CD in the ileum, while increasing VH and VH/CD (p<0.05). Additionally, the addition of 150 and 300 mg/kg of BAs significantly increased the expression levels of zonula occludens-1 (ZO-1) and occludin in the jejunum. Simultaneously 150mg/kg and 300mg/kg BAs increased the total short-chain fatty acids (SCFA) concentrations in the jejunum and cecum(p < 0.05).Supplementation with BAs resulted in a significant increase in the ɑ-diversity of cecal microbiota and a decrease in the abundance of Proteobacteria in the cecum. The addition of 150 mg/kg of BAs significantly reduced the abundance of Bacteroidetes and increased the abundance of Firmicutes. Moreover,Linear discriminant analysis Effect Size analysis (LEfSe) showed that the abundances of bacteria producing SCFA and bile salt hydrolases (BSH) were increased in the BAs-treated group. Furthermore, Spearman's analysis showed that the genus Balutia, which is negatively correlated with visceral fat area, was positively correlated with serum high-density lipoprotein cholesterol (HDL-C), while Clostridium was positively correlated with intestinal VH and VH/CD. In conclusion, BAs can be considered an effective feed additive for geese, as they increased SCFA concentration, improve lipid metabolism and intestinal health by enhancing the intestinal mucosal barrier, improving intestinal morphology, and altering the cecal microbiota structure.

Effect of Plasma Exchange Treatment in Patients with Hypertriglyceridemia-Induced Acute Pancreatitis.

Background and Objectives: To describe the clinical and biological characteristics of patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) and to evaluate the effectiveness of therapeutic plasma exchange (TPE) in the management of HTG-AP. Materials and Methods: A cross-sectional study was conducted on 81 HTG-AP patients (30 treated with TPE and 51 treated conventionally). The main outcome was a decrease in serum triglyceride levels (<11.3 mmol/L) within 48 h of hospitalization. Results: The mean age of participants was 45.3 ± 8.7 years, and 82.7% were male. Abdominal pain was the most frequent clinical sign (100%), followed by dyspepsia (87.7%), nausea or vomiting (72.8%), and a bloated stomach (61.7%). The HTG-AP patients treated with TPE had significantly lower calcemia and creatinemia levels but higher triglyceride levels than those who received conservative treatment. They also had more severe diseases than those treated conservatively. All patients in the TPE group were admitted to the ICU, whereas the ICU admission rate in the non-TPE group was 5.9%. The TPE patients were more likely to experience a rapid decrease in triglyceride levels within 48 h of treatment than those treated conventionally (73.3% vs. 49.0%, p = 0.03, respectively). The decrease in triglyceride levels did not depend on the age, gender, or comorbidities of the HTG-AP patients or the severity of disease. However, TPE and early treatment in the first 12 h of disease onset were effective in rapidly reducing serum triglyceride levels (adjusted OR = 3.00, p = 0.04 and aOR = 7.98, p = 0.02, respectively). Conclusions: This report demonstrates the effectiveness of early TPE in reducing triglyceride levels among HTG-AP patients. More randomized clinical trials studies with a large sample size and post-discharge follow-up are needed to confirm the effectiveness of TPE methods in managing HTG-AP.

Clinical results and mechanism of action of icosapent ethyl.

Serum triglyceride concentration is considered as an additional component that often contributes to residual cardiovascular risk in patients already at high risk; these considerations have led to several clinical studies aimed at evaluating the efficacy of supplements based on omega-3 fatty acids in reducing serum triglyceride levels and consequently cardiovascular risk. Although partially inconclusive and contradictory, these clinical trials laid the foundations for the implementation of the REDUCE-IT and EVAPORATE studies, in which the use of a purified derivative of eicosapentaenoic acid, icosapent ethyl, resulted in a significant reduction both of the composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke and of the reduction in the volumetric progression up to the induction of a real regression of the coronary atheromatous plaques detected by computerized coronary angiography tomography. Surprisingly, these brilliant results seem to be, at least in part, not related to the reduction of triglyceride concentration. The purpose of this article is to examine the latest evidence regarding icosapent ethyl therapy, describing the results of the main clinical trials performed to date and formulating hypotheses on the potential mechanisms of action of this fascinating molecule.

Clinical effectiveness of α-lipoic acid, myo-inositol and propolis supplementation on metabolic profiles and liver function in obese patients with NAFLD: A randomized controlled clinical trial

To compare the effects of α-lipoic acid (ALA), myo-inositol (MI) and propolis supplementation on metabolic parameters and liver function in obese patients with non-alcoholic fatty liver disease (NAFLD) METHODS: Ninety-two obese patients with NAFLD were randomly allocated into one of the four groups (ALA, MI, propolis, and control groups) for 8 weeks. At pre-and post-intervention, anthropometric measures, metabolic parameters and liver function were assessed. Clinical effectiveness was assessed using Absolute Risk Reduction (ARR) and Number Needed to Treat (NNT). After 8 weeks, apart from waist-to-hip ratio, all studied anthropometric measures decreased significantly in each of the groups over the trial. Although the greatest improvements in glycemic indices were observed in MI group (p<0.05), the differences among the groups were not significant. Control group showed the greatest reduction in serum triglyceride level (p=0.026) while the greatest improvements in serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were observed in MI group (p=0.043, p=0.019 and p=0.041, respectively). Alanine aminotransferase (ALT) levels reduced significantly in all groups, particularly in propolis group (p=0.012). The greatest reduction in serum aspartate transaminase (AST) level was observed in control group (p<0.001), however, the difference among the groups was statistically marginal (p=0.058). The estimated NNTs for one grade reduction in liver steatosis for MI, ALA and propolis supplementation compared with control group were 1.5, 2.2 and 3, respectively. Dietary recommendation for weight loss accompanied by MI and then ALA supplementation improved metabolic parameters and liver steatosis. "Registered under ClinicalTrials.gov Identifier no: IRCT20100209003320N22".

Chaperonin counteracts diet-induced non-alcoholic fatty liver disease by aiding sirtuin 3 in the control of fatty acid oxidation.

The mitochondrial chaperonin heat shock protein (HSP) 60 is indispensable in protein folding and the mitochondrial stress response; however, its role in nutrient metabolism remains uncertain. This study investigated the role of HSP60 in diet-induced non-alcoholic fatty liver disease (NAFLD). We studied human biopsies from individuals with NAFLD, murine high-fat-diet (HFD; a diet with 60% energy from fat)-induced obesity (DIO), transgenic (Tg) mice overexpressing Hsp60 (Hsp60-Tg), and human HepG2 cells transfected with HSP60 cDNA or with HSP60 siRNA. Histomorphometry was used to assess hepatic steatosis, biochemistry kits were used to measure insulin resistance and glucose tolerance, and an automated home cage phenotyping system was used to assess energy expenditure. Body fat was assessed using MRI. Macrophage infiltration, the lipid oxidation marker 4-hydroxy-2-nonenal (4-HNE) and the oxidative damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected using immunohistochemistry. Intracellular lipid droplets were evaluated by Nile red staining. Expression of HSP60, and markers of lipogenesis and fatty acid oxidation were quantified using RT-PCR and immunoblotting. Investigations were analysed using the two-way ANOVA test. Decreased HSP60 expression correlated with severe steatosis in human NAFLD biopsies and murine DIO. Hsp60-Tg mice developed less body fat, had reduced serum triglyceride levels, lower levels of insulin resistance and higher serum adiponectin levels than wild-type mice upon HFD feeding. Respiratory quotient profile indicated that fat in Hsp60-Tg mice may be metabolised to meet energy demands. Hsp60-Tg mice showed amelioration of HFD-mediated hepatic steatosis, M1/M2 macrophage dysregulation, and 4-HNE and 8-OHdG overproduction. Forced HSP60 expression reduced the mitochondrial unfolded protein response, while preserving mitochondrial respiratory complex activity and enhancing fatty acid oxidation. Furthermore, HSP60 knockdown enhanced intracellular lipid formation and loss of sirtuin 3 (SIRT3) signalling in HepG2 cells upon incubation with palmitic acid (PA). Forced HSP60 expression improved SIRT3 signalling and repressed PA-mediated intracellular lipid formation. SIRT3 inhibition compromised HSP60-induced promotion of AMP-activated protein kinase (AMPK) phosphorylation and peroxisome proliferator-activated receptor α (PPARα levels), while also decreasing levels of fatty acid oxidation markers. Mitochondrial HSP60 promotes fatty acid oxidation while repressing mitochondrial stress and inflammation to ameliorate the development of NAFLD by preserving SIRT3 signalling. This study reveals the hepatoprotective effects of HSP60 and indicates that HSP60 could play a fundamental role in the development of therapeutics for NAFLD or type 2 diabetes.

Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: Results of the BROADEN study: Volanesorsen in FPLD; The BROADEN Study

BackgroundVolanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations. ObjectiveThe present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes. MethodsBROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open-label extension and post-treatment follow-up periods. Patients received weekly subcutaneous volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides at 3 months. Secondary endpoints included relative percent change in hepatic fat fraction (HFF), visceral adiposity, and glycated hemoglobin levels. ResultsForty patients (11 men, 29 women) were enrolled, majority of whom were aged <65 years (mean, 47 years) and White. Least squares mean (LSM) percent change in triglycerides from baseline to 3 months was −88% (95% CI, −134 to −43) in the volanesorsen group versus –22% (95% CI, −61 to 18) in the placebo group, with a difference in LSM of −67% (95% CI, –104 to –30; P=0.0009). Volanesorsen induced a significant LSM relative reduction in HFF of 53% at month 12 versus placebo (observed mean [SD]: 9.7 [7.65] vs. 18.0 [8.89]; P=0.0039). No statistically significant changes were noted in body volume measurements (fat, liver, spleen, visceral/subcutaneous adipose tissue) or glycated hemoglobin. Serious adverse events in patients assigned to volanesorsen included 1 case each of sarcoidosis, anaphylactic reaction, and systemic inflammatory response syndrome. ConclusionIn BROADEN, volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD.

Therapeutic plasma exchange for the management of hypertriglyceridemia-induced acute pancreatitis

<b>BACKGROUND:</b> Hypertriglyceridemia (HTG) is the third-most important cause of acute pancreatitis (AP) and its early diagnosis is essential to prevent AP-associated morbidity and mortality. Therapeutic plasma exchange (TPE) is a promising treatment option for improving patient outcomes and prognosis in HTG-induced AP (HTG-AP). <b>OBJECTIVE:</b> This study assessed the severity of disease in patients with HTG-AP and evaluated the therapeutic effects, safety, and procedural challenges of TPE in its management. <b>METHODS:</b> Patients with HTG-AP, diagnosed according to the Atlanta classification, and exhibiting serum triglyceride (TG) concentrations ≥11.3 mmol/L were included in the study. Consenting patients received TPE using the PRISMAFLEX^® system (TPE group), and the remaining were treated in accordance with the guidelines of Vietnam's Ministry of Health, 2015 (non-TPE group). The duration of hospital or intensive care unit (ICU) stay in patients and mortality rates were compared between the TPE and non-TPE groups. The reduction in serum TG levels was also evaluated in the TPE group. <b>RESULTS:</b> This prospective study included 165 patients with HTG-AP (<i>n</i> = 83, TPE group; <i>n</i> = 82, non-TPE group). The mean age of the patients was 41.0 ± 9.3 years. The duration of hospital and ICU stay was significantly lower in the TPE group compared to that of the non-TPE group (<i>P</i> < 0.05). A significant reduction in TG levels over baseline was noted in patients who received TPE (77%; <i>P</i> < 0.05), which was observed after the first TPE session (70.81%; <i>P</i> < 0.05). <b>CONCLUSION:</b> TPE using the PRISMAFLEX^® system is safe and well-tolerated in patients with HTG-AP and is associated with minimal technical constraints.

Hypertriglyceridemia-Induced Acute Pancreatitis - Course, Outcome, and Comparison with Non-Hypertriglyceridemia Associated Pancreatitis.

Although hypertriglyceridemia (HTG) is a well-established cause of acute pancreatitis (AP), there are no definitive management guidelines. Studies comparing clinical severity and outcome of hypertriglyceridemia-induced acute pancreatitis (HTGAP) and non- HTGAP are scarce. Hence, the present study was undertaken. All consecutive patients admitted with AP from January 2017 to August 2021 at university teaching hospital were included in this study. Data with regards to patient demographics; clinical, laboratory, and radiologic parameters; management strategies; and outcome were collected and compared between HTGAP and non-HTGAP patients. Overall, 550 patients with AP were admitted during the study period, of which 21 (3.8%) were HTG related. Mean age of HTGAP patients was 34.3 years (M: F = 14:7), and the mean serum triglyceride (TG) levels on admission were 3,718.9 mg/dL (range 1,094-11,991). Insulin infusion therapy was used in 18 patients with HTGAP and the target TG levels of ≤500 mg/dL was achieved in 4.2 days (mean). Compared to non-HTGAP patients, HTGAP patients had higher body mass index (29.2 vs. 25.6), higher clinical (BISAP 2.6 vs. 2.06) and radiologic severity scores (CT severity score 7.5 v/s 4.8), and required prolonged hospital stay (12.9 vs. 6.5 days). HTGAP occurred in young patients with high BMI and was associated with more severe disease, that required prolonged hospitalization than patients with non-HTGAP. Insulin infusion therapy was effective in reducing serum TG levels.

Pharmacological Evaluation of Beta‐Hydroxifosphocarnitine in No‐Alcoholic Steatohepatitis Induced in Rats

Aim Evaluate the pharmacological effect of Β-Hydroxyphosphocarnitine (β-HFC) on non-alcoholic steatohepatitis induced in rats. Introduction Non-alcoholic steatohepatitis (NASH) is a disease with high prevalence, usually accompanied on metabolic syndrome. Currently the treatment to NASH is pioglitazone. However, it is reported that pioglitazone causes several side effects reason to stop treatment. L-carnitine has pharmacological effect in the metabolic syndrome, but it is poorly absorbed. The β-HFC is an analogue of L-carnitine that has shown effect on metabolic syndrome and maintaining its pharmacological properties. Method The NASH model was developed in male Wistar rats by ingesting carbonated drink as a source of fructose, coconut oil and carbon tetrachloride. 3 groups were formed with NASH (n = 8); NASH, NASH -β-HFC and NASH-pioglitazone. Another 3 groups of healthy rats (n = 8); control, control-β-HFC and control-pioglitazone. The effect of β-HFC in NASH rats was evaluated by histological sections of the liver with Masson's hematoxylin eosin and trichromic staining. Quantification of liver enzymes, triglycerides, cholesterol and glucose in serum by spectrophotometric kit. Insulin levels were determined by Elisa. Results We previously reported that β-HFC reduced serum triglyceride levels in NASH rats. The levels of glucose, insulin and nitric oxide (NO) were quantified and are the ones that we will report on this occasion. Insulin levels were low in the NASH rats even with the β-HFC treatment compared to the control rats, (25.9 ± 6, 30.0 ± 10 and 121.1 ± 69.5 ng / ml respectively). The pancreas can be damaged by excess fatty acids (FA), altering insulin production. No significant difference was observed in glucose levels between the control and NASH groups (123.2 ± 50.6 and 134.3 ± 19.1 mg/dL respectively). High glucose levels would be expected in NASH rats, however, since insulin resistance is not observed, it could justify that glucose is not elevated. NO is a source of production of reactive species. The rats with NASH showed higher levels of NO than those of the control group (0.054, 0.01 µM / µl respectively). β-HFC was shown to reduce NO levels in rats with NASH (0.03µM / µl). β-HFC enhances the fatty acid oxidation process which can result in decreased production of reactive species. Conclusion: β-HFC enhances key alterations for NASH progression such as DNL and NO production. Conclusion: β-HFC promises to be effective for the treatment of NAHS by improving key alterations for the progression of NASH such as DNL and NO production.

Chemical Constituents of the Bulbs of Scilla peruviana and Their Pancreatic Lipase Inhibitory Activity.

Scilla species are used as medicinal plants and contain lanosterol-type triterpene glycosides. The phytochemical investigation of the bulbs of Scilla peruviana led to the isolation of 17 compounds, including three new rearranged pentacyclic-lanosterol glycosides (1–3) and two new homoisoflavanone glycosides (12 and 13). The structures of the undescribed compounds were determined by extensive spectroscopic analyses, including two-dimensional (2D) NMR. Among the triterpene glycosides, 2, 3, and 6 showed significant pancreatic lipase inhibitory activity in a concentration-dependent manner in vitro. The oral administration of scillascilloside D-2 (6) reduced serum triglyceride levels in a dose-dependent manner in soybean oil-loaded mice.

Effects of ingested nanomaterials on tissue distribution of co-ingested zinc and iron in normal and zinc-deficient mice

Cellulose nanofibers (CNF) reduced serum triglyceride levels in rats when co-administered with heavy cream by gavage. Do CNF and other nanomaterials (NMs) alter the tissue distribution and retention of co-administered metal ions? We evaluated whether 5 different NMs affected tissue distribution of co-ingested 65Zn++ and 59Fe+++ in zinc-replete versus zinc-deficient mice. Male C57BL/6J mice were fed either zinc-replete or zinc-deficient diets for 3 weeks, followed by gavage with NM suspensions in water containing both 65ZnCl2 and 59FeCl3. Urine and feces were measured for 48 h post-gavage. Mice were euthanized and samples of 22 tissues were collected and analyzed for 65Zn and 59Fe in a gamma counter. Our data show that zinc deficiency alters the tissue distribution of 65Zn but not of 59Fe, indicating that zinc and iron homeostasis are regulated by distinct mechanisms. Among the tested NMs, soluble starch-coated chitosan nanoparticles, cellulose nanocrystals, and TiO2 reduced Zn and Fe tissue retention in zinc-deficient but not in zinc-replete animals.

Cost-Effectiveness of Passion Fruit Albedo versus Turmeric in the Glycemic and Lipaemic Control of People with Type 2 Diabetes: Randomized Clinical Trial

Background Robust evidence has related yellow passion fruit albedo and long turmeric to the metabolic and glycemic control of diabetes. Aim To analyze the incremental cost-effectiveness of the flour made from yellow passion fruit albedo versus long turmeric merged with piperine in the glycemic and lipid control of individuals with type 2 diabetes. Method Eighty-nine patients were enrolled in this randomized, placebo-controlled, clinical trial for 120 days. The first group was prescribed 500 mg capsules, three times a day, of yellow passion fruit albedo flour (FAMA). The second group was prescribed long turmeric capsules (500 mg), merged with piperine (5 mg) (CURPI), at fasting. The third group followed the standard advice recommendations, and ingested a placebo of carboxymethyl cellulose (500 mg) at fasting. Results The group using FAMA showed a higher reduction (−5.9%) of glycemia after fasting, compared to placebo (+9%), and CURPI (−3.2%) (p < 0.05). Regarding HbA1c, the study observed a significant and similar statistical reduction (−0.8%) in the intervention groups, in contrast with the placebo group (p < 0.05). The reduction in HOMA-IR in the CURPI group (−9.4%) was higher than the other groups (p < 0.05). The CURPI group also showed a higher reduction of serum triglyceride levels (−20.8%) compared to the placebo (−0.09%) and FAMA (+1.8%) (p < 0.05) groups. Conclusion It was concluded that turmeric is the most cost-effective in comparison with yellow passion fruit albedo, because of its decrease in the levels of triglycerides and HOMA-IR, even when adjusted for confounding variables. On the other hand, HbA1c cost-effectiveness relation was similar.

EFFICACY AND SAFETY OF IV INSULIN INFUSION FOR MANAGEMENT OF HYPERTRIGLYCERIDEMIC PANCREATITIS

SESSION TITLE: Critical Care Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Hypertriglyceridemic pancreatitis (HTGP) portends significant morbidity and mortality, and management involves rapid lowering of serum triglycerides (TG). Both plasmapheresis (PL) and intravenous (IV) insulin infusions are effective for this purpose, although comparative analyses of these interventions have not been performed. Furthermore, the role of IV insulin in patients with HTGP without diabetes remains unknown. We aimed to investigate these questions in a cohort of patients hospitalized for HTGP at a tertiary care center. METHODS: A retrospective chart review of patients hospitalized for acute HTGP between January 1, 2001 and December 31, 2018 was performed. Patients were stratified according to treatment modality: IV insulin infusion, PL+/- IV insulin, or conservative management. Efficacy of TG-lowering and clinical outcomes were compared between groups. RESULTS: One hundred and four patients with HTGP were identified. Seventy-eight patients (75 %) were treated with IV insulin, 6 (5.8%) were treated with PL, and 20 (19.2%) received conservative management. Admission TG levels were significantly higher in the IV insulin and PL vs. conservative group (p = 0.009). The percent decline in TG levels from admission to hospital discharge was 80.8% ±13.2%, 90.0% ± 5.6%, 63.9% ± 30.5% among the IV insulin, PL, and conservative groups, respectively (p=0.0214), with no statistically significant differences seen between IV insulin and PL groups. Eighty (80.0%) patients had diabetes mellitus, the majority of whom received IV insulin (81.3%). Among patients without diabetes, 54.2% received IV insulin only. Hospital complications, hypoglycemic events, and LOS did not differ between patients with and without diabetes who received IV insulin. CONCLUSIONS: Intravenous insulin infusion is a safe and effective method for reducing serum triglyceride levels in both diabetic and non-diabetic patients diagnosed with acute HTGP. CLINICAL IMPLICATIONS: IV insulin infusion is effective and safe for management of acute HTPG when compared to conservative management or plasmapheresis. Given the challenges associated with use of plasmapheresis and its limited clinical utility, IV insulin infusion should be considered as a first line therapy for treatment of this entity in both diabetic and non-diabetic individuals. DISCLOSURES: No relevant relationships by Hasan Ahmad Hasan Albitar, source=Web Response No relevant relationships by Adham Alkurashi, source=Web Response No relevant relationships by Yahya Almodallal, source=Web Response no disclosure on file for Tiffany Cortes; No relevant relationships by Kristen Gonzales, source=Web Response No relevant relationships by Sumedh Hoskote, source=Web Response No relevant relationships by Maria Hurtado, source=Web Response No relevant relationships by vivek iyer, source=Web Response no disclosure on file for Prashant Jagtap; No relevant relationships by Vinaya Simha, source=Web Response