Reduced Serum Triglyceride Research Articles

Analysis of Intravenous Insulin Dosing Requirements for Treatment of Severe Hypertriglyceridemia.

Purpose: Insulin infusion therapy is commonly utilized for treatment of severe hypertriglyceridemia, however, data supporting a standardized dosing approach is lacking. This study aimed to determine the average initial insulin dose utilized for treatment of hypertriglyceridemia and the associated reduction in serum triglycerides. Methods: This single-center, retrospective, descriptive analysis conducted at an academic medical center included adult hospitalized patients with serum triglyceride levels greater than 1000 mg/dL receiving treatment with an intravenous insulin infusion between November 2017 and August 2020. Data was extracted from the electronic medical record. The primary outcome was the mean weight-based intravenous insulin dose resulting in resolution of hypertriglyceridemia. Secondary outcomes included time to resolution of hypertriglyceridemia, adverse events associated with insulin treatment, incidence of rebound hypertriglyceridemia, and use of additional lipid-lowering therapies. Results: Data from 32 hospital encounters was analyzed. The mean initial triglyceride level was 3229 mg/dL. The average insulin doses observed on days 1 and 2 of therapy were 0.07 and 0.05 units/kg/hour, respectively. The mean percent triglyceride reduction at 48 hours was 40%. Mean time to resolution of hypertriglyceridemia, discontinuation of insulin infusion, or discharge was 5.7 days. Hypoglycemia and hypokalemia were observed in 9% and 29% of patients, respectively. Conclusion: The results of this study provide new guidance for insulin dosing for hypertriglyceridemia. Serum potassium levels and blood glucose should be monitored closely during therapy.

Plasmapheresis compared with conventional treatment for hypertriglyceridemia-induced acute pancreatitis: A systematic review and meta-analysis.

The treatment of acute pancreatitis (AP) induced by hypertriglyceridemia (HTG) remains controversial with regard to plasmapheresis vs conventional treatment. We reviewed relevant articles to explore the efficacy of plasmapheresis in the management of HTG-induced AP. We systematically reviewed studies that compared plasmapheresis with conventional treatment for HTG-induced AP using three databases: PubMed, Embase, and Cochrane Library, as well as relevant references. The primary outcomes were 24 h triglyceride reduction rate and in-hospital mortality. A total of 791 articles were retrieved. Finally, 15 observational studies (1080 participants) were included, most of which were historical cohort studies. Compared with conventional treatment, plasmapheresis assisted in the reduction of serum triglyceride (TG) levels in the first 24 h after hospital admission (standardized mean difference [SMD]: 0.58; 95% confidence interval [CI]: 0.17 to 0.99; P=0.005). However, it resulted in increased hospitalization costs (thousand yuan) (weighted mean difference [WMD]: 24.32; 95% CI: 12.96 to 35.68; P < 0.001). With regard to in-hospital mortality, although the mortality rate in the plasmapheresis group was higher than that in the conventional treatment group (relative risk [RR]: 1.74; 95% CI: 1.03 to 2.94; P=0.038), the result was disturbed by confounding factors as per the subgroup and sensitivity analysis, as well as trial sequential analysis (TSA). No significant differences were found in other outcomes, including systematic complications, local complications, the requirement for surgery, and hospitalization duration. The effect of plasmapheresis in HTG-induced AP is not superior to that of conventional treatment, even resulting in a greater economic burden to patients and health care system. High quality randomized control trials are required to obtain a more a definitive understanding of this issue.

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.

The effect of Xuezhikang capsule on gene expression profile in brown adipose tissue of obese spontaneously hypertensive rats

Ethnopharmacological relevanceObesity is a critical threat to global health, and brown adipose tissue (BAT) is a potential target for the treatment of obesity and comorbidities. Xuezhikang Capsule (XZK), an extract of red yeast rice, has remarkable clinical efficacy and is widely used for the treatment of hyperlipidemia and coronary heart disease. However, its modulatory effect on BAT remains unknown. Aim of this studyThe aim of this study was to investigate the protective mechanism of XZK in the obese spontaneously hypertensive rat (SHR) model by evaluating the regulatory effect of XZK on the BAT gene profile through transcriptome sequencing. Materials and methodsThe SHRs were randomly divided into four groups: the standard chow diet (STD) group, the STD supplemented with 126 mg/kg of XZK group, the high-fat diet (HFD) group, and the HFD supplemented with 126 mg/kg of XZK group. All SHRs were fed for 18 weeks. The metabolic phenotypes, including body weight, fat mass, oral glucose tolerance test (OGTT), and serum glucose and lipid levels, was evaluated, and hematoxylin and eosin staining (H&E) staining was performed to evaluate the adipose tissue histopathological phenotype. Transcriptome sequencing was performed to determine the mechanism by which XZK improves the metabolic phenotype and the expression of key differential expression genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR). ResultsXZK inhibited HFD-induced weight gain and adipose tissue remodeling in SHRs and prevented hypertrophy of epididymal adipocytes and maintained the brown fat phenotype. XZK intervention also improved glucose and lipid metabolism in SHRs, as suggested by a reduction in serum triglyceride (TG), low-density cholesterol (LDL-C), and fasting blood glucose (FBG) levels as well as increasing in serum high-density cholesterol (HDL-C) levels. Transcriptome sequencing analysis confirmed the regulatory effect of XZK on the gene expression profile of BAT, and the expression patterns of 45 genes were reversed by the XZK intervention. Additionally, the results of the transcriptome analysis of 10 genes that are important for brown fat function were in line with the results of qRT-PCR. ConclusionsXZK protected SHRs from HFD-induced obesity, inhibited fat accumulation and improved glucolipid metabolism. Additionally, the protective effect of XZK on the overall metabolism of obese SHRs might partly be related to its regulatory effect on the BAT gene expression profile. These findings might provide novel therapeutic strategies for obesity-related metabolic diseases in traditional Chinese medicine (TCM).

Amelioration of hyperglycemia and hyperlipidemia in a high-fat diet-fed mice by supplementation of a developed optimized polyherbal formulation.

This study evaluated in vivo anti-diabetic and anti-obesity activity of a polyherbal formulation's methanolic extract containing an optimized ratio of edible seeds (Salvia hispanica, Chenopodium quinoa, Nelumbo nucifera). Diet-induced obese mice model (C57BL/6) was developed by feeding the mice ahigh-fat diet for 10weeks resulting in hyperglycemia and obesity. Different doses (125, 250 and 500mg/kg of body weight) of formulation were administered orally daily for 6weeks. Fasting blood glucose and body weight were monitored throughout the study. At the end of the study, serum parameters were analyzed and histological examinations were performed. There was a significant reduction in fasting blood glucose levels and body weight in animal groups receiving polyherbal formulation. Lipid profile was improved as revealed by a reduction in serum triglycerides and total cholesterol. Histological study showed an improvement in liver, kidney and pancreatic sections of treated mice. High-performance thin layer chromatography was performed to identify the phytochemicals responsible for the above-mentioned bioactivities. The results revealed the presence of flavonoid (rutin) in seeds of N.nucifera and in the polyherbal formulation. For the first time, this study demonstrated the anti-diabetic and anti-obesity potential of the optimized formulation. The formulation can be used as a potential therapy for management of diabesity.

E4orf1 Prevents Progression of Fatty Liver Disease in Mice on High Fat Diet.

Non-alcoholic fatty liver disease (NAFLD) covers a broad spectrum of liver diseases ranging from steatosis to cirrhosis. There are limited data on prevention of hepatic steatosis or its progression to liver disease. Here, we tested if either transgenic (Tg) doxycycline-induced expression in adipose tissue of E4orf1 (E4), an adenoviral protein, or dietary fat restriction attenuated hepatic steatosis or its progression in mice. Twelve to fourteen-week-old TgE4 mice (E4 group) and control mice were exposed to a 60% (Kcal) high fat diet (HFD) for 20 weeks, while another group of mice on HFD for 10 weeks were switched to a chow diet (chow group) for another 10 weeks. Glycemic control was determined at weeks 10 and 20. Tissues were collected for gene and protein analysis at sacrifice. Compared to control, diet reversal significantly reduced body weight in the chow group, whereas E4 expression attenuated weight gain, despite HFD. E4 mice evinced significantly improved glucose clearance, lower endogenous insulin secretion, reduced serum triglycerides, attenuated hepatic steatosis and inflammation. Interestingly, in spite of weight loss and lower liver fat, chow mice showed significant upregulation of hepatic genes involved in lipid metabolism. Despite HFD, E4 prevents hepatic lipid accumulation and progression of hepatic steatosis, while diet reversal maintains hepatic health, but is unable to improve molecular changes.

Wax apple (Syzygiumsamarangense) fruit extract ameliorates endothelial dysfunction and liver damage in high cholesterol diet-fed rats

Background and aimWax apple fruit (Syzygium samarangense) is one of the most popular tropical fruit in Asia, and contains several essential nutrients. Therefore, this study explored the effects of the wax apple fruit extract on a high-cholesterol diet-induced vascular endothelial dysfunction and fatty liver in rats. Experimental procedureMale Sprague Dawley rats were fed a diet with 1.5% cholesterol (HCD) for 8 weeks, and were given wax apple fruit extract (50 and 100 mg/kg/day) orally for the last 4 weeks. After 8 weeks, blood sample, thoracic aorta, and liver were collected and processed for biochemical and histological analysis. Additionally, vascular endothelial function and the protein expression of oxidative stress markers in aortae were evaluated. Results and conclusionWax apple reduced serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), but increased high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, the liver levels of TG and TC were reduced in wax apple-treated hypercholesterolemic rats. Histological studies revealed that wax apple ameliorated HCD-induced morphologic changes of aortic and liver tissues of rats. In aortic tissues, the impaired endothelium-dependent responses to acetylcholine, the reduced nitric oxide (NO) contents, the elevated endothelin (ET)-1 contents, and the increased expression of NADPH oxidase subunit p47phox and 4-hydroxynonenal in HCD-fed rats were reversed by wax apple treatment. These results suggest that oral administration of wax apple improves vascular dysfunction and damage in hypercholesterolemic rats possibly through increasing NO bioavailability, decreasing ET-1 levels and reducing oxidative stress. Furthermore, wax apple ameliorates the HCD-induced fatty liver in rats.

Incidence and clinical characteristics of hypertriglyceridemic acute pancreatitis: A retrospective single-center study.

BACKGROUNDThe incidence of hypertriglyceridemic acute pancreatitis (HTG-AP) has increased yearly, but updated population-based estimates on the incidence of HTG-AP are lacking. Reducing serum triglyceride (TG) levels quickly is crucial in the early treatment of HTG-AP. Decreased serum TG levels are treated by non-invasive methods, which include anti-lipidemic agents, heparin, low-molecular weight heparin, and insulin, and invasive methods, such as blood purification including hemoperfusion (HP), plasmapheresis, and continuous renal replacement therapy. However, authoritative guidelines have not been established. Early selection of appropriate treatment is important and beneficial in controlling the development of HTG-AP.AIMTo evaluate the effect between patients treated with intravenous insulin (INS) and HP to guide clinical treatment.METHODSWe retrospectively reviewed 371 patients with HTG-AP enrolled in the Department of Fujian Provincial Hospital form April 2012 to March 2021. The inpatient medical and radiologic records were reviewed to determine clinical features, severity, complications, mortality, recurrence rate, and treatment. Multivariate logistic regression analyses were used to analyze risk factors for severe HTG-AP. Propensity score matching was used to compare the clinical outcomes of INS and HP.RESULTSA total of 371 patients met the HTG-AP criteria. The incidence of HTG-AP was increased by approximately 2.6 times during the 10 years (8.4% in April 2012-March 2013 and 22.3% in April 2020-March 2021). The highest incidence rate of acute pancreatitis was observed for men in the age group of 30-39 years. The amylase level was elevated in 80.1% of patients but was only three times the normal value in 46.9% of patients. The frequency of severe acute pancreatitis (26.9%), organ failure (31.5%), rate of recurrence (32.9%), and mortality (3.0%) of HTG-AP was high. Improved Marshall score, modified computed tomography severity index score, baseline TG, baseline amylase, C-reactive protein (CRP), albumin, aspartate aminotransferase, low-density lipoprotein cholesterol, urea nitrogen, creatinine, calcium, hemoglobin, free triiodothyronine, admission to intensive care unit, and mortality were significantly different between patients with different grades of severity (P < 0.050). Multivariate logistic regression analysis confirmed that high CRP [P = 0.005, odds ratio (OR) = 1.011, 95%CI: 1.003-1.019], low calcium (P = 0.003, OR = 0.016, 95%CI: 0.001-0.239), and low albumin (P = 0.023, OR = 0.821, 95%CI: 0.693-0.973) were risk factors of severe HTG-AP. After propensity score matching adjusted by sex, age, severity of HTG-AP, and baseline TG, the serum TG significantly decreased in patients treated with INS (P < 0.000) and HP (P < 0.000) within 48 h. However, the clearance rate of TG (57.24 ± 33.70% vs 56.38 ± 33.61%, P = 0.927) and length of stay (13.04 ± 7.92 d vs 12.35 ± 6.40 d, P = 0.730) did not differ between the two groups.CONCLUSIONThe incidence of HTG-AP exhibited a significant increase, remarkable severity, and recurrent trend. Patients with mild and moderately severe acute pancreatitis can be treated effectively with INS safely and effectively without HP.

Clinically Relevant Dose of Pemafibrate, a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator (SPPARMα), Lowers Serum Triglyceride Levels by Targeting Hepatic PPARα in Mice.

Pemafibrate (PEM) is a novel lipid-lowering drug classified as a selective peroxisome proliferator-activated receptor α (PPARα) modulator whose binding efficiency to PPARα is superior to that of fibrates. This agent is also useful for non-alcoholic fatty liver disease and primary biliary cholangitis with dyslipidemia. The dose of PEM used in some previous mouse experiments is often much higher than the clinical dose in humans; however, the precise mechanism of reduced serum triglyceride (TG) for the clinical dose of PEM has not been fully evaluated. To address this issue, PEM at a clinically relevant dose (0.1 mg/kg/day) or relatively high dose (0.3 mg/kg/day) was administered to male C57BL/6J mice for 14 days. Clinical dose PEM sufficiently lowered circulating TG levels without apparent hepatotoxicity in mice, likely due to hepatic PPARα stimulation and the enhancement of fatty acid uptake and β-oxidation. Interestingly, PPARα was activated only in the liver by PEM and not in other tissues. The clinical dose of PEM also increased serum/hepatic fibroblast growth factor 21 (FGF21) without enhancing hepatic lipid peroxide 4-hydroxynonenal or inflammatory signaling. In conclusion, a clinically relevant dose of PEM in mice efficiently and safely reduced serum TG and increased FGF21 targeting hepatic PPARα. These findings may help explain the multiple beneficial effects of PEM observed in the clinical setting.

Effect of simvastatin on osteogenesis of the extremity bones in aging rats

ABSTRACT Purpose Simvastatin is a prodrug of the potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The main purpose of the current study is to assess the accurate function of simvastatin on osteoporosis of extremity bones in aging rats. Materials and methods Fifty 15-month-old SD rats were divided into five groups (four simvastatin groups and one control group). The rats in four simvastatin groups were fed with different doses of simvastatin (5, 10, 20, and 40 mg/kg/d, respectively) for 3 months, whereas the rats in control group were fed the equal physiological saline. Calcium (Ca), phosphorus (P), and the lipid spectrum in serum were measured. Biochemical markers of bone metabolism, osteocalcin (OC), and tartrate-resistant acid phosphatase (Trap-5b), were analyzed using ELISA. The content of adipocytes in bone marrow was analyzed by histological staining. Finally, the bone quality of the femur and tibia were evaluated using dual-energy X-ray absorptiometry (DEXA), peri-quantity CT (pQCT), and the 3-point bending biomechanical test. Results Simvastatin reduced serum triglycerides (TG), and 10 mg/kg/d of simvastatin significantly reduced the content of adipocytes in bone marrow compared to the control group. However, statistically significant differences between the simvastatin groups and the control group were not found in the CA, P, OC, Trap-5b, or the evaluation indexes of bone quality from DEXA, pQCT, and biomechanical tests. Conclusion Simvastatin could not prevent osteoporosis of the extremity bones in aging rats.

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo

Ethnopharmacological relevanceAlthough Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. Aim of the studyAssess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. Materials and methodsEnzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. ResultsBoth extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 μg/μL for O-E and 1.8 μg/μL for O-A) than the positive control (Orlistat) (0.07 μg/μL). The IC50 of α-amylase was higher (41.8 μg/μL for O-E and 25.2 μg/μL for O-A) than the Acarbose (2.5 μg/μL); while α-glucosidase results showed not statistically differences between groups (∼1.7 μg/μL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 μg/μL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 μg/μL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. ConclusionsBoth extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

A Comparative Study on Clinical Evaluation of the Hypolipidemic Effects of Allium sativum, Trigonella foenum-graecum, Commiphora mukul, Picrorhiza kurroa, and Piper nigrum: A Pilot Study.

BackgroundCardiovascular disease is a leading cause of morbidity and mortality. Therefore, it is essential to prevent cardiovascular diseases by correcting modifiable risk factors such as lowering lipid levels, lowering blood pressure, improving eating habits, giving up smoking, etc. The present study assessed the efficacy of herbal preparation containing Allium sativum (A. sativum), Commiphora mukul (C. mukul), and Trigonella foenum-graecum (T. foenum-graecum) in patients with hyperlipidemia.MethodologyPatients were given extracts of A. sativum 350 mg, T. foenum-graecum 350 mg, C. mukul 200 mg, Picrorhiza kurroa (P. kurroa) 200 mg, and Piper nigrum (P. nigrum) 5 mg. Unichem Laboratories, Mumbai, provided placebo tablets similar in shape and size to herbal tablets. Patients were assessed for compliance, and a complete lipid profile was done at DO, D15, D46, D76, and D106. In addition, total cholesterol and high-density lipoprotein-cholesterol (HDL-C) serum triglyceride were estimated by the respective methods throughout the study.ResultsThe weight of the patients remained stable, the mean weight before being 65.42 ± 8.35 kg and after completion of the study being 65.42 ± 8.35 kg. There were no changes in the ECG during or after the drug therapy in any of the patients. Group A comprised nine patients, and group B had ten patients. Serum creatinine (mg %) was 0.94 and 0.95, fasting blood sugar mg (%) was 111.05 and 99.63, and postprandial blood sugar (mg %) was 150.89 and 147.94 on pre-treatment and post-treatment, respectively. The mean serum triglyceride levels in group A were 271.11, 261.11, 293.89, 167.22, and 128.89, and serum HDL- C levels were 46.11, 46.11, 54.44, 52.22, and 54.44. Serum triglyceride levels in group B were 268, 268.5, 202, 171, and 116, and serum HDL- C levels were 48.5, 48, 50, 50, and 53.5 on day 0, 15, 46, 76, and 106, respectively. A significant reduction in total cholesterol levels was observed on D46, D76, and D106, with a maximum reduction on D76 (25.36%). Similarly, a reduction in serum triglyceride was also observed on D46, D76, and D106, with a maximum reduction on D106 (52.02%). A significant difference was observed (P <0.05). There was also a significant reduction of low-density lipoprotein cholesterol (LDL-C) on D46, D76, and D106, with the maximum reduction on D76 (28.79%). There was a significant rise of HDL-C on D46 and D106, with a maximum rise on D106 (15.41%). A significant difference was observed (P <0.05).ConclusionThe study drugs are safe and efficacious in reducing the total cholesterol, serum triglycerides, LDL-C levels, and increasing HDL-C levels.

Cardioprotective Effects and in-silico Antioxidant Mechanism of L-Ergothioneine in Experimental Type-2 Diabetic Rats.

Diabetic cardiotoxicity is commonly associated with oxidative injury, inflammation, and endothelial dysfunction. L-ergothioneine (L-egt), a diet-derived amino acid, has been reported to decrease mortality and risk of cardiovascular injury, provides cytoprotection to tissues exposed to oxidative damage, and prevents diabetes-induced perturbation. This study investigated the cardioprotective effects of L-egt on diabetes-induced cardiovascular injuries and its probable mechanism of action. Twenty-four male Sprague-Dawley rats were divided into non-diabetic (n = 6) and diabetic groups (n = 18). Six weeks after the induction of diabetes, the diabetic rats were divided into three groups (n = 6) and administered distilled water, L-egt (35mg/kg), and losartan (20mg/kg) by oral gavage for six weeks. Blood glucose and mean arterial pressure (MAP) were recorded pre-and post-treatment, while biochemical, ELISA, and RT-qPCR analyses were conducted to determine inflammatory, injury-related and antioxidant biomarkers in cardiac tissue after euthanasia. Also, an in-silico study, including docking and molecular dynamic simulations of L-egt toward the Keap1- Nrf2 protein complex, was done to provide a basis for the molecular antioxidant mechanism of Legt. Administration of L-egt to diabetic animals reduced serum triglyceride, water intake, MAP, biomarkers of cardiac injury (CK-MB, CRP), lipid peroxidation, and inflammation. Also, Legt increased body weight, antioxidant enzymes, upregulated Nrf2, HO-1, NQO1 expression, and decreased Keap1 expression. The in-silico study showed that L-egt inhibits the Keap1-Nrf2 complex by binding to the active site of Nrf2 protein, thereby preventing its degradation. L-egt protects against diabetes-induced cardiovascular injury via the upregulation of the Keap1-Nrf2 pathway and its downstream cytoprotective antioxidants.

Fecal microbiota and metabolomics revealed the effect of long-term consumption of gallic acid on canine lipid metabolism and gut health.

Gallic acid (GA) is a natural polyphenolic compound with many health benefits. To assess the potential risk of long-term consumption of GA to gut health, healthy dogs were fed a basal diet supplemented with GA (0%, 0.02%, 0.04%, and 0.08%) for 45 d, and fecal microbiota and metabolomics were evaluated. This study demonstrated that GA supplementation regulated serum lipid metabolism by reducing serum triglyceride, fat digestibility, and Bacteroidetes/Firmicutes ratio. In addition, the relative abundance of Parasutterella was significantly lower, and the SCFAs-producing bacteria were increased along with fecal acetate and total SCFAs contents accumulation in the 0.08% GA group. Metabolomics data further elucidated that 0.08% GA significantly affected carbohydrate metabolism by downregulating succinic acid in fece, thereby alleviating inflammation and oxidative stress. Overall, this study confirmed the beneficial effects of long-term consumption of GA on lipid metabolism and gut health, and the optimal level of GA supplementation was 0.08%.

Hypolipidemic activity of lactic acid bacteria: Adjunct therapy for potential probiotics.

BackgroundIndividuals with hyperlipidemia are two times more likely to develop atherosclerotic cardiovascular disease (ASCVD) as opposed to those with controlled serum total cholesterol (TC) levels. Considering the documented adverse events of the current lipid-lowering medications which ultimately affect patient’s compliance, substantial efforts have been made to develop new therapeutic strategies. Probiotics, on the other hand, are reported to have lipid-lowering activity with the added benefit of being generally well-tolerated making it an appealing adjuvant therapy.MethodsA total of fifty Lactic acid bacteria (LAB) were isolated from raw milk (human and animal) and dairy products. Isolates demonstrating promising in vitro cholesterol removal capabilities were morphologically and biochemically characterized. Lastly, two bacterial candidates were selected for evaluation of their potential hypolipidemic activity using a laboratory animal model. Statistical differences between the means were analyzed by one-way analysis of variance (ANOVA) followed by Tukey’s post-hoc test. A p-value < 0.05 was considered statistically significant.ResultsMost of the isolates demonstrated an in vitro cholesterol removal activity. The six LAB isolates showing the highest cholesterol removal activity (36.5–55.6%) were morphologically and biochemically identified as Lactobacillus, Pediococcus, and Lactococcus species. The results demonstrated two promising antihyperlipidemic candidates, a Lactococcus lactis ssp. lactis with an in vivo significant reduction of serum triglycerides (TG) levels by 34.3%, and a Pediococcus sp. that was able to significantly reduce both the serum TC and TG levels by 17.3% and 47.0%, respectively, as compared to the diet-induced hyperlipidemic animal group.ConclusionThis study further supports the growing evidence regarding the antihyperlipidemic activity among probiotics, presenting them as a promising therapeutic approach for the management of hyperlipidemia.

Effect of unripe fruit extract of Momordica charantia on total cholesterol, total triglyceride and blood lipoproteins in the blood of rats with hyperlipidemia

Hyperlipidemia is a major risk factor for the development of cardiovascular disease. In this study, the effects of an unripe fruit extract of Momordica charantia on total cholesterol, total triglyceride and lipoproteins in the blood of mice with hyperlipidemia were investigated. In this study, 28 adult male Wistar rats weighing 210 to 250 g were selected and randomly divided into four groups of seven. One group was on a normal diet and the other groups were fed a high-fat diet for 8 weeks to develop hyperlipidemia. Experimental groups in this study were included group 1: control, oral administration of normal food without any drugs or extracts. Group 2: hyperlipidemia mice, feeding with normal food. Group 3: hyperlipidemia mice with a diet containing 4%. Group 4: hyperlipidemia mice with a diet containing 8%. The animals were fed by gavage at a dose of 4% and 8% of M. charantia powder solution for 15 days. Blood samples were taken and the level of total cholesterol, total triglyceride, and high-density lipoproteins (HDL) were measured enzymatically. The amount of low-density lipoproteins was calculated by Friedewald's formula. Data were analyzed using the analysis of variance. Experimental results showed that immature fruit powder of M. charantia quarantine significantly reduced serum triglycerides in group 8% mice fed rats fed a high-fat diet. Moreover, immature fruit powder of M. charantia increased the level of high-density lipoproteins. There was a statistically significant difference between the level of cholesterol and the level of low-density proteins (LDL). The highest reduction belonged to the group receiving immature powder. The results of the experiment showed that the unripe fruit extract of M. charantia has strong antilipidemic effects on rats fed with a high-fat diet.

Management of hypertriglyceridemia-induced pancreatitis – A review of updates from the past decade

Hypertriglyceridemia-induced acute-pancreatitis (HTG-AP) is an important etiology of acute pancreatitis (AP). The treatment includes general management of AP with bowel rest, analgesia, and venous thromboembolism prophylaxis. Specific treatment of HTG-AP focuses on reducing serum triglyceride (TG) levels. Various modalities have been used, including heparin infusion, insulin infusion, plasmapheresis, and double filtration plasmapheresis (DFPP). However, the extent to which TG reduction translates into a clinical response remains unclear. This review highlights the emerging evidence on the management of HTG-AP. Insulin therapy and plasmapheresis remain treatment options to reduce TG. DFPP is an emerging treatment modality to reduce TG levels in patients with AP. However, to what extent this translates into a better clinical response is yet to be answered in large and prospective study designs.

Association between Pemafibrate Therapy and Triglyceride to HDL-Cholesterol Ratio.

Background: Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator, which was demonstrated to reduce serum triglyceride level with few drug-related adverse events in phase II and III clinical trials. However, its clinical implication in real-world practice remains unknown. Triglyceride/HDL-cholesterol ratio is a surrogate of small dense LDL-cholesterol, which is a newly proposed cardiovascular risk factor independent of LDL-cholesterol levels. Methods: Consecutive patients who received pemafibrate between April 2020 and September 2021 and continued therapy for at least 3 months were included in this retrospective analysis. The primary outcome was the trend in triglyceride/HDL-cholesterol ratio during the 3-month treatment period. The change in cardiovascular event rate between the one-year pre-treatment period and the on-treatment period was also analyzed. Results: A total of 19 patients (median age 63 years, 74% men) were included and continued pemafibrate therapy for 3 months without any drug-related adverse events. Sixteen were add-on and three were conversions from other fibrates. Triglyceride/HDL-cholesterol ratio decreased significantly from 5.85 (4.19, 16.1) to 3.14 (2.39, 4.62) (p < 0.001). The cardiovascular event rate decreased significantly from 0.632 events/year to 0.080 events/year (p < 0.001). Conclusions: Pemafibrate therapy might have the potential to lower triglyceride/HDL-cholesterol ratio and decrease cardiovascular events.

Meta-analysis of the effects of quinoa (Chenopodium quinoa) interventions on blood lipids

ObjectiveThe purpose of the current study is to conduct a meta-analysis of published randomized controlled trials to explore the quantitative effect of quinoa supplementation on serum lipid concentrations. MethodsOnline databases, including Web of Science, Scopus, and PubMed, were systematically searched. A comprehensive literature review was performed based on English reports of randomized controlled trials of quinoa on lipid profiles in adults, which were published up to July 2020. Weighted mean differences (WMD) with a 95% confidence interval (CI) were assigned as the ultimate effects of using random models. Study quality was assessed by using the Cochran score, and a meta-analysis was conducted. ResultsFive RCTs with eight intervention arms, including 291 participants, were selected for the present meta-analysis. The intervention period was between 4 and 12 weeks. The results showed doses higher than 50 g of quinoa consumption and duration more than six weeks of intervention significantly reduced serum triglyceride (TG) levels (WMD: −0.864 mg/dl; 95% CI: −1.286, −0.442, P < 0.001) and (WMD: −0.623 mg/dl; 95% CI: −1.015, −0.232, P = 0.002), respectively. In general, quinoa supplementation did not have a significant effect on concentrations of high-density lipoprotein cholesterol (HDL-C) levels (WMD: −0.145 mg/dl; 95% CI: −0.377, 0.086, P = 0.218), low-density lipoprotein cholesterol (LDL-C) levels, (WMD: 0.082 mg/dl; 95% CI: −0.150, 0.314, P = 0.489), and total cholesterol (TC) levels)WMD: − 0.036 mg/dl; 95% CI: − 0.267, 0.195, P = 0.759(. ConclusionThis study reveals quinoa supplementation in doses higher than 50 g/day and the duration more than six weeks significantly reduced TG levels. However, further studies in this area are recommended to understand the potential mechanisms of quinoa on blood lipids.

Abstract 112: Sars-cov-2 Infection Promotes Dyslipidemia And Non-alcoholic Steatohepatitis In Diet-induced Obese Golden Syrian Hamsters

Background: Obesity, non-alcoholic steatohepatitis (NASH) and dyslipidemia have been associated with severe forms of COVID-19. To better understand the impact of SARS-CoV-2 infection on dyslipidemia and NASH, we investigated the impact of infection with the beta variant of the SARS-CoV-2 in lean and high fat/cholesterol/fructose diet-induced obese Golden Syrian hamsters. Methods: Lean (chow diet fed) or diet-induced obese hamsters were infected intranasally with the beta variant of the SARS-CoV-2. At baseline (before infection) and at 4-, 7-, 10- and 25-days post-infection (dpi), blood and organs were collected for biochemistry and histology analyses. Results: Early after SARS-CoV-2 infection, lung viral load and pulmonary inflammation were not different between lean and obese hamsters. However, compared to lean hamsters, obese hamsters showed significantly higher MCP-1 serum levels at baseline and after infection, had impaired recovery (lower resolution of lung lesions at 10 dpi, lower body weight regain at 25 dpi), and exhibited higher pulmonary fibrosis at 25 dpi. In both lean and obese hamsters, SARS-CoV-2 infection led to reduction in serum triglycerides and HDL-cholesterol levels at 4 and 7 dpi. However, obese hamsters remained hypertriglyceridemic and hypercholesterolemic, while SARS-CoV-2 infection led to significant elevation of serum free fatty acids and LDL-cholesterol levels at 4 and 7 dpi in those obese individuals, as compared to baseline levels. Despite the substantial weight loss induced by SARS-CoV-2 infection, the NASH phenotype of obese hamsters was maintained, with significantly higher liver steatosis, inflammation, hepatocyte ballooning and fibrosis scores from day 0 to 25 dpi. Additionally, obese hamsters showed significantly higher liver fibrosis at 25 dpi, as compared to lean hamsters. Conclusion: Our data indicate that SARS-CoV-2 infection promotes dyslipidemia and non-alcoholic steatohepatitis in diet-induced obese Golden Syrian hamsters. This model will be useful to investigate the mechanisms leading to severe forms of COVID-19 seen in obese patients with dyslipidemia and NASH.