Serum Total Cholesterol Concentrations Research Articles

Taurine Improves Lipid Metabolism and Increases Resistance to Oxidative Stress.

Calorie restriction (CR) by 30-40% decreases morbidity of age-related diseases and prolongs the lifespan of various laboratory animal species. Taurine (2-aminoethanesulfonic acid) is an important nutrient for lipid metabolism as it conjugates bile acids. Here, we investigated how taurine supplementation induces effects similar to the CR beneficial effects. Sprague Dawley rats were fed a diet containing different taurine concentrations (0, 0.5, 1.0, 3.0, 5.0%) to analyze the effects on growth, blood, and hepatic parameters. Rats fed a 5% taurine-supplemented diet showed a significant decrease in visceral fat weight, compared with control rats. Moreover, there were significant decreases in the serum total cholesterol, hepatic cholesterol and triglyceride concentrations in the taurine-supplemented groups compared with the control group in a dose-dependent manner. These results were associated with decreased mRNA expression of fatty acid synthase, and increased mRNA expression of carnitine palmitoyltransferase 1α. C57BL/6 mice were fed a 5.0% taurine-supplemented diet, and their response to 3-nitropropionic acid-induced oxidative stress was analyzed. The rate of weight loss due to oxidative stress decreased and the survival rate significantly increased in the taurine-supplemented groups compared with the control group. Finally, cells were treated with 100 μM taurine and their resistance to UV-induced oxidative stress was analyzed. We found that the p53-Chk1 pathway was less activated in taurine-treated cells compared with control cells. Furthermore, damage to cells evaluated by oxidative stress indicators revealed a reduction in oxidative damage with taurine treatment. These findings suggest that taurine partially acts as a CR mimetic.

Perfluorooctanoic acid activates multiple nuclear receptor pathways and skews expression of genes regulating cholesterol homeostasis in liver of humanized PPARα mice fed an American diet

Humans are exposed to per- and polyfluoroalkyl substances (PFAS) in their drinking water, food, air, dust, and by direct use of consumer products. Increased concentrations of serum total cholesterol and low density lipoprotein cholesterol are among the endpoints best supported by epidemiology. The objectives of this study were to generate a new model for examining PFAS-induced dyslipidemia and to conduct molecular studies to better define mechanism(s) of action. We tested the hypothesis that perfluorooctanoic acid (PFOA) exposure at a human-relevant level dysregulates expression of genes controlling cholesterol homeostasis in livers of mice expressing human PPARα (hPPARα). Female and male hPPARα and PPARα null mice were fed a diet based on the “What we eat in America” analysis and exposed to PFOA in drinking water (8 μM) for 6 weeks. This resulted in a serum PFOA concentration of 48 μg/ml. PFOA increased liver mass, which was associated with histologically-evident lipid accumulation. Pooled analyses of serum lipoprotein cholesterol suggest that PFOA increased serum cholesterol, particularly in male mice. PFOA induced PPARα and constitutive androstane receptor target gene expression in liver. Expression of genes in four pathways regulating cholesterol homeostasis were also measured. PFOA decreased expression of Hmgcr in a PPARα-dependent manner. PFOA decreased expression of Ldlr and Cyp7a1 in a PPARα-independent manner. Apob expression was not changed. Sex differences were evident. This novel study design (hPPARα mice, American diet, long term exposure) generated new insight on the effects of PFOA on cholesterol regulation in the liver and the role of hPPARα.

Effects of cold temperature and fat supplementation on growth performance and rumen and blood parameters in early fattening stage of Korean cattle steers

We investigated the effects of cold ambient temperatures and the supplementation of rumen-protected fat (RPF) on the growth performance, rumen fermentation parameters, and blood metabolic parameters of Korean cattle steers during the early fattening stage. Twenty Korean cattle steers (body weight = 356.5 ± 3.72 kg, age = 16.8 ± 0.34 months) were divided into two groups: 10 steers were fed a conventional concentrate (control), and 10 steers were fed a concentrate supplemented with 8 g/kg RPF (treatment). Steers were fed a concentrate at 1.6% body weight and 3 kg tall fescue hay daily for 12 weeks in 2016: January 8 to February 2 (P1), February 3 to March 3 (P2), and March 4 to April 1 (P3). Body weight was measured, and blood and rumen fluid were collected four times from each steer: at the start of the experiment, and then at 4-week intervals. The mean indoor temperatures during P1 (−7.37 ℃) and P2 (–2.96℃) were lower (P < 0.001) than the mean P3 temperature (6.22 ℃). These lower temperatures were within the range that causes mild to moderate cold stress (CS) in other cattle breeds. By contrast, the mean indoor temperature during P3 is considered thermoneutral. The average daily gain (P = 0.39 and P = 0.16) and gain-to-feed ratio (P = 0.26 and P = 0.57) were not affected by RPF supplementation or time-period. Total dry matter, crude protein, ether extract, neutral detergent fiber, and acid detergent fiber intakes per body weight were higher (all P < 0.001) in colder P1 or P2 compared to other time periods, but these variables were not affected (P ≥ 0.31) by RPF supplementation, except ether extract intake. Ruminal total VFA concentrations were higher (P = 0.001) in a colder January than in other months, but these were not affected (P = 0.26) by RPF supplementation. The ruminal propionate proportion was higher (P < 0.001) in a colder January than in other months, whereas the butyrate proportion was lower (P = 0.01). Serum triglyceride (P = 0.007), total cholesterol (P = 0.001), and high-density lipoprotein (P = 0.03) concentrations were lower during colder months. RPF supplementation increased (P = 0.008) serum cholesterol concentrations. Our results indicate that mild to moderate CS may not affect Korean cattle, as cattle growth performance was not affected by colder temperatures, although concentrate and forage intakes were increased, and some changes in blood metabolic and ruminal parameters were observed. The 8 g/kg RPF supplementation did not improve growth performance under cold conditions, although it did not decrease intake and ruminal total VFA concentration.

The Effects of Linoleic Acid Consumption on Lipid Risk Markers for Cardiovascular Disease in Healthy Individuals: A Review of Human Intervention Trials.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Risk factors for developing this disease include high serum concentrations of total cholesterol, triglycerides, low-density lipoproteins, very-low density lipoproteins, and low concentrations of high-density lipoproteins. One proposed dietary strategy for decreasing risk factors involves replacing a portion of dietary saturated fatty acids with mono- and polyunsaturated fatty acids (PUFAs). The essential omega-6 PUFA, linoleic acid (LA), is suggested to decrease the risk for CVD by affecting these lipid risk markers. Reviewing human intervention trials will provide further evidence of the effects of LA consumption on risk factors for CVD. PubMed was used to search for peer-reviewed articles. The purpose of this review was: (1) To summarize human intervention trials that studied the effects of LA consumption on lipid risk markers for CVD in healthy individuals, (2) to provide mechanistic details, and (3) to provide recommendations regarding the consumption of LA to decrease the lipid risk markers for CVD. The results from this review provided evidence that LA consumption decreases CVD lipid risk markers in healthy individuals.

Effects of Evolocumab on Carotid Intima-Media Thickness and Clinical Parameters in Patients Taking a Statin.

We determined the effects of evolocumab, a fully human monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9, on carotid intima-media thickness (IMT) and the factors associated with the change in carotid IMT in patients taking a statin. The change in carotid mean and maximum IMT before and after the initiation of evolocumab treatment was retrospectively analyzed in 229 statin-treated patients. The changes in clinical parameters, including serum lipid concentrations, were also evaluated. Evolocumab significantly reduced the increase in carotid mean and maximum IMT (0.09 ± 0.13 mm/year to −0.04 ± 0.16 mm/year, p < 0.001 and 0.17 ± 0.38 mm/year to 0.08 ± 0.47 mm/year, p = 0.02). Evolocumab reduced serum total cholesterol, low-density lipoprotein-cholesterol, triglyceride, and lipoprotein (a) concentrations (each p < 0.001), and increased serum high-density lipoprotein (HDL)-cholesterol concentrations (p = 0.01). Multiple linear regression analysis revealed that the change in HDL-cholesterol (standard coefficient (β) = −0.120, p = 0.04) and carotid mean IMT (β = −0.467, p < 0.001) were independently correlated with the change in carotid mean IMT during the administration of evolocumab, whereas the change in HDL-cholesterol (β = −0.208, p = 0.002) and log-triglyceride (β = −0.167, p = 0.01) independently correlated with the change in carotid maximum IMT. Evolocumab reduced the increase in carotid IMT in patients taking a statin. These results suggest that evolocumab is protective against carotid atherosclerosis in patients undergoing statin therapy.

Comparison of protective effects between oat β-glucan and phenol-rich extracts in hyperlipidemic ICR mice

β-Glucan in oat is widely considered as the main ingredient for the anti-hypercholesterol effects; however, phenolic compounds in oat are also regarded to possess potential activities against dyslipidemia. In order to understand the underlying mechanisms thoroughly, it is of great significance to evaluate and compare the hypolipidemic properties exerted by oat phenol-rich extract (PE) and β-glucan extract (GE) in hyperlipidemic ICR mice induced by high-fat diet. The study was conducted for 12 weeks. Both PE and GE showed a significant hypocholesterolemic action by reducing the concentration of serum total cholesterol (TC), low density lipoprotein cholesterol and hepatic TC. Only PE reduced the hepatic triacylglycerol (TG), inhibited hepatic 3-hydroxy-3-methylglutary CoA reductase activities and improved the hepatic antioxidant defense system. However, GE significantly increased fecal excretion of neutral cholesterol and bile acids. This study demonstrated that not only β-glucan but also oat phenolic acids contributed to a preventive effect on hyperlipidemia. Based on the cholesterol metabolism and antioxidant defense system, the effects of the two functional components of oat were exerted in different ways.

Defects in High Density Lipoprotein metabolism and hepatic steatosis in mice with liver-specific ablation of Hepatocyte Nuclear Factor 4A

BackgroundAberrant concentration, structure and functionality of High Density Lipoprotein (HDL) are associated with many prevalent diseases, including cardiovascular disease and non-alcoholic fatty liver disease (NAFLD). Mice with liver-specific ablation of Hnf4α (H4LivKO) present steatosis and dyslipidemia by mechanisms that are not completely understood. The aim of this study was to explore the role of liver HNF4A in HDL metabolism and the development of steatosis. Methods and resultsSerum and tissue samples were obtained from 6-weeks old H4LivKO mice and their littermate controls. Liver and serum lipids were measured and HDL structure and functionality were assessed. Global gene expression changes in the liver were analyzed by expression arrays, validations were performed by RT-qPCR and DNA-protein interactions were studied by chromatin immunoprecipitation (ChIP). H4LivKO mice presented liver steatosis, increased liver triglyceride content and decreased concentration of serum total cholesterol, HDL cholesterol, triglycerides, phospholipids and cholesteryl esters. Most classes of phospholipids showed significant changes in species ratio and sphingosine-1-phosphate (S1P) levels were reduced. H4LivKO serum was enriched in the smaller, denser HDL particles, devoid of APOA2 and APOM apolipoproteins, exhibiting decreased activity of paraoxonase-1 but retaining macrophage cholesterol efflux capacity and phospho-AKT activation in endothelial cells. Global gene expression analysis revealed the association of liver HNF4A with known and novel regulators of HDL metabolism as well as NAFLD-susceptibility genes. ConclusionsHNF4A ablation in mouse liver causes hepatic steatosis, perturbations in HDL structure and function and significant global changes in gene expression. This study reveals new targets of HNF4A involved in HDL metabolism and the development of steatosis and enriches our knowledge on HDL functionality in NAFLD.

Therapeutic Effects of Garlic on Hepatic Steatosis in Nonalcoholic Fatty Liver Disease Patients: A Randomized Clinical Trial.

Background and AimsEmerging evidence suggests that garlic (Allium sativum L.) and its bioactive components can mitigate hepatic steatosis by the modulation of hepatic lipid metabolism. We aimed to assess the efficacy of the garlic administration on hepatic steatosis in patients with NAFLD.Patients and MethodsThis clinical trial was conducted on adult patients with ultrasound-diagnosed NAFLD. Eligible participants were randomly assigned, with the use of the stratified blocked procedure, to receive 800 mg garlic or placebo for 15 weeks. The primary outcome was the improvement in the hepatic steatosis diagnosed by ultrasound technique after 15 weeks of intervention.ResultsA total of 110 patients underwent randomization, and 98 patients completed the trial. Twenty-four (51.1%) patients in the garlic group achieved improvement in the hepatic steatosis compared to eight (15.7%) patients in the placebo group with the relative risk of 5.6 (95% CI: 2.17 to 14.5; P=0.001), which remained significant after adjusting for baseline value of hepatic steatosis. There were significant reductions in weight and serum ALT, AST, FBS, Hb A1C, total cholesterol, LDL-cholesterol, and TG concentration with the garlic intake compared to placebo (P<0.05). The results were also significant after adjusting for weight change, energy intake, and physical activity. No serious adverse effects were observed with the garlic intake.ConclusionThe intake of garlic powder was accompanied by a significant improvement in the hepatic steatosis and comorbidity related to this condition among subjects with NAFLD.

Association of Dietary Phytosterols with Cardiovascular Disease Biomarkers in Humans.

Cardiovascular disease (CVD) is a leading cause of death worldwide. Elevated concentrations of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are major lipid biomarkers that contribute to the risk of CVD. Phytosterols well known for their cholesterol-lowering ability, are non-nutritive compounds that are naturally found in plant-based foods and can be classified into plant sterols and plant stanols. Numerous clinical trials demonstrated that 2 g phytosterols per day have LDL-C lowering efficacy ranges of 8-10%. Some observational studies also showed an inverse association between phytosterols and LDL-C reduction. Beyond the cholesterol-lowering beneficial effects of phytosterols, the association of phytosterols with CVD risk events such as coronary artery disease and premature atherosclerosis in sitosterolemia patients have also been reported. Furthermore, there is an increasing demand to determine the association of circulating phytosterols with vascular health biomarkers such as arterial stiffness biomarkers. Therefore, this review aims to examine the ability of phytosterols for CVD risk prevention by reviewing the current data that looks at the association between dietary phytosterols intake and serum lipid biomarkers, and the impact of circulating phytosterols level on vascular health biomarkers. The clinical studies in which the impact of phytosterols on vascular function is investigated show minor but beneficial phytosterols effects over vascular health. The aforementioned vascular health biomarkers are pulse wave velocity, augmentation index, and arterial blood pressure. The current review will serve to begin to address the research gap that exists between the association of dietary phytosterols with CVD risk biomarkers.

Association between apolipoprotein E gene polymorphism and the risk of coronary artery disease in Hakka postmenopausal women in southern China

BackgroundApolipoprotein E (APOE) is involved in the pathogenesis of atherosclerosis and conveys a higher risk of coronary artery disease (CAD). The aim of the present study was to investigate the possible association between APOE gene polymorphism and the risk of CAD in postmenopausal Hakka women in southern China.MethodsThe APOE genotypes of 653 CAD patients and 646 control participants were determined by the polymerase chain reaction (PCR) and hybridization to a Sinochip.ResultsThe prevalence of each APOE genotype differed between CAD patients and control participants (P = 0.011). The E3/E3 genotype was the most common and the E2/E2 genotype was the least common in the study sample. Moreover, the presence of ε4 allele was associated with higher serum concentrations of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C), and lower concentration of high-density lipoprotein-cholesterol (HDL-C). Multiple logistic regression analysis revealed that participants with ε4 allele have a significantly higher risk of CAD after adjustment for the presence of diabetes mellitus and hypertension, and their serum uric acid, TC, and LDL-C concentrations (adjusted odds ratio (OR) 1.50, 95% confidence interval (CI) 1.10–2.05, P = 0.010).ConclusionsThe present results suggest that APOE polymorphism is associated with a higher risk of CAD in postmenopausal Hakka women in southern China.

Do different bariatric surgical procedures influence plasma levels of matrix metalloproteinase-2, -7, and -9 among patients with type 2 diabetes mellitus?

BACKGROUNDBariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus (T2DM) management. Abnormal lipid deposition in visceral organs, especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix (ECM) remodeling allows adipose expansion, and matrix metalloproteinases (MMPs) play essential roles in ECM construction. MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2, -7, and -9 increase in patients with obesity and metabolic syndromes or T2DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass (GB) and sleeve gastrectomy (SG).METHODSWe performed GB in 23 and SG in 19 obese patients with T2DM. We measured body weight, waist circumference, body mass index (BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar (FBS), hemoglobin A1c (HbA1c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTSTwenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged 40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to 24.4 ± 2.4 kg/m2, HbA1c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/dL to 117.7 ± 37.5 mg/dL 2 years post-operation (P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre- and post-GB were similar even 2 years post-operation (P = 0.107, 0.258, and 0.466, respectively). The SG group revealed similar results: BMI decreased from 36.2 ± 5.1 to 26.9 ± 4.7 kg/m2, HbA1c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/dL to 95.1 ± 3.1 mg/dL (P < 0.001). The serum MMP-2, -7, and -9 levels pre- and post-SG were not different (P = 0.083, 0.869, and 0.1, respectively).CONCLUSIONImprovements in obesity and T2DM induced by bariatric surgery might be the result of MMP-2, -7, or -9 independent pathways.

The Effects of the Dietary Supplement Cardioflex on Reducing Cardiovascular Disease Risk Factors in Adults

Abstract Objectives The overall objective was to determine the effects of the multi-nutrient dietary supplement Cardioflex, independent of diet or lifestyle changes, to reduce cardiovascular disease (CVD) risk factors in adults. Methods A 90-day, randomized, double-blind, parallel design clinical study was performed from February to June 2019. Participants received one serving (10 g) of Cardioflex or an isocaloric maltodextrin placebo daily. Blood pressure was measured using an automatic sphygmomanometer. A 1-min arterial test (accelerated plethysmography; APG) and a 5-min heart-rate-variability (HRV) test were conducted using a Meridian digital pulse wave analyzer. Serum concentrations of total cholesterol (TC), triglycerides (TG) and high-density lipoprotein (HDL) were measured using Vitros-350 chemistry analyzer. Analysis of covariance was used to compare the post treatment biomarkers of the two groups using IBM SPSS Statistics (v.25). Results A total of 67 participants (placebo = 33, Cardioflex = 34) with a mean age of 48.3 ± 8.8 years, completed the study. Cardioflex improved HRV (+5%; P = 0.04) compared to the placebo (−9%). Although both groups saw improvements in blood pressure, heart rate, APG age, body mass index, waist circumference, TC, low-density lipoprotein (LDL), and TG, there was no significant difference (P &amp;gt; 0.05) between groups. Interestingly, the placebo significantly (P = 0.04) lowered (−18.7%) TC compared to Cardioflex (−15%). Conclusions Cardioflex supplement may benefit HRV; a parameter associated with CVD. However, more research is needed to understand its effects on CVD. Also, our study also highlights the ‘placebo effect’ that can occur in parallel design clinical trials. Funding Sources Funding was provided by MITACs and Innotech Nutrition.

Serum Non-esterified Fatty Acids and Risk of Incident Stroke in Older Adults: The Cardiovascular Health Study

Abstract Objectives Significant associations between plasma total non-esterified fatty acid (NEFA) concentrations and incident ischemic stroke have been reported in some but not all prospective cohort studies. Given the functional and structural diversity among circulating NEFA, the association of individual or sub-groups of circulating NEFAs may provide additional insight into their relationship with incident stroke. We hypothesized fasting serum monounsaturated, n-6 polyunsaturated (PUFA) and n-3 PUFA NEFA are inversely associated, and saturated and trans NEFA are positively associated with incident stroke. Methods We analyzed the incidence of stroke among Cardiovascular Health Study (CHS) participants who were free of stroke in 1996–1997 (baseline) and had an archived fasting serum sample (N = 2028). At baseline, mean age was 77.8 ± 4.5, body mass index (BMI) was 26.7 ± 4.4 and 61% were female. A total of 38 individual NEFAs were measured using gas chromatography. Cox regression was used to evaluate the association of individual and 5 sub-group (saturated, monounsaturated, n-6 PUFA, n-3 PUFA and trans) NEFAs with incident stroke, adjusting for age, sex, race and field center (model 1); model 1 covariates plus serum albumin, smoking, education, physical activity, alcohol consumption, eGFR, BMI, aspirin use, waist circumference, hypertension, prevalent diabetes and total serum cholesterol concentration (model 2). Results A total of 338 cases of incident stroke occurred during median follow-up of 10.5 years. In the fully adjusted model 2, individuals in the highest quartile of serum 16:1n-7 had a 56% higher risk of stroke (quartiles 4 versus 1, hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.08–2.25; P-trend = 0.02); highest quartile of total n-6 PUFA NEFA had a 40% higher risk (HR, 1.40; 95% CI, 0.99–1.98; P-trend = 0.03); and highest quartile of 20:3n-6 had a 53% higher risk (HR, 1.53; 95% CI, 1.09–2.14; P-trend = 0.01). No significant associations were observed between saturated, n-3 PUFA, and trans NEFAs with incident stroke. Conclusions These data suggest a positive association between fasting serum 16:1n-7, 20:3n-6 and total n-6 PUFA NEFAs with incident stroke in CHS participants. No significant associations were observed for the other individual or sub-groups of NEFAs. Funding Sources NIH and USDA.

Mulberry Fruit Hot Water Extract Attenuates Adipose Tissue Inflammation with the Regulation of Macrophage Infiltration and M1/M2 Type Switching in Rats Fed a High-Fat Diet

Abstract Objectives This study aimed to investigate the effects of mulberry fruit extract (ME) on adipose tissue inflammation in rats fed a high-fat diet. Methods Male, Sprague-Dawley rats were divided into 4 groups and fed either a low-fat diet (LF, 10% kcal fat), high-fat diet (HF, 45% kcal fat), HF with 0.5% mulberry fruit extract (HF + LME), or HF with 1% mulberry fruit extract (HF + HME) for 14 weeks. Results The serum triglyceride (TG) and total cholesterol (TC) concentrations were significantly lower in the ME supplemented groups. In white adipose tissue (WAT), the HF + HME significantly down-regulated the mRNA expression of adipogenic genes, such as sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ), and adipocyte protein2 (aP2). The HF + HME significantly decreased both levels of mRNA and protein of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein 1 (MCP1). The crown-like structure (CLS) and the mRNA expression of F4/80, a pan-macrophage marker, tended to be reduced in the ME supplemented groups. The ME supplemented groups down-regulated the mRNA expression of pro-inflammatory M1 macrophage markers, such as a cluster of differentiation (CD) 68, CD11c, and nitric oxide synthase 2 (NOS2). On the other hand, the mRNA expression of CD163 and arginase1 (ARG1), an anti-inflammatory M2 macrophage marker, was up-regulated by the HF + HME. Conclusions From these results, it is suggested that the ME might modulate the macrophage infiltration and phenotypic switching and alleviate adipose tissue inflammation in rats fed a high-fat diet. Funding Sources None.

Prophylactic and Therapeutic Effect of Aqueous Stem Extract of Costus afer on Lipids and Atherogenic Profile of Albino Rats in Acetaminophen Induced Liver Toxicity

Background: Medicinal plants are widely used in Nigeria because they are believed to be effective in the treatment of various medical conditions and are also easily accessable with minimal side effect.&#x0D; Aim: This study evaluates the prophylactic and therapeutic effects of different doses (200 mg/kg, 400 mg/kg and 800 mg/kg body weight) of Costus afer on lipid profile of 50 male albino rats.&#x0D; Methodology: The research study was divided into 2 phases with 25 rats used for each phases. The 25 rats used for each phase were randomly selected into 5 groups with each group containing 5 rats. The rats used for the prophylactic phase were induced with 800 mg/kg body weight paracetamol for liver toxicity after administration of the various concentrations of aqueous stem extract of C. afer for 28 days while those used during the therapeutic phase were administered with the various concentrations of aqueous stem extract of C. afer following confirmation of liver toxicity using 800 mg/kg body weight acetaminophen. The effect of the aqueous extract was assessed by measuring the serum concentration of total cholesterol, triglycerides and high density lipoprotein using Randox reagent, while low density lipoprotein was calculated from the other parameters. Atherogenic ratios were also computed. The result obtained from the experiment was subjected to statistical analysis using Graph pad prism version 5.3 and values were considered significant at p&lt;0.05.&#x0D; Results: Total cholesterol, triglycerides and LDL levels were significantly (p&lt;0.05) reduced and HDL significantly increased in the treatment groups (prophylactic and therapeutic phases) compared to the positive control. When both phases were compared, total cholesterol and triglycerides showed significant (p&lt;0.05) difference in concentration in groups fed with 400 mg/kg, 200 mgkg while LDL-C showed significant (p&lt;0.05) variation between the two phases only at 400 mg/kg body weight. The extracts were also found to significantly (p&lt;0.05) reduce the atherogenic status of the albino rats in both phases of treatment and between each treatment phase.&#x0D; Conclusion: Findings from this study suggest that Costus afer possesses the ability to regulate paracetamol induced dyslipidaemia and improve the anti-atherogenic status of treated albino rats.

A Dose-Dependent Effect of Carnipure® Tartrate Supplementation on Endurance Capacity, Recovery, and Body Composition in an Exercise Rat Model.

The objective of this work is to investigate the effects of Carnipure® Tartrate (CT) supplementation with or without exercise on endurance capacity, recovery, and fatigue by assessing time to exhaustion as well as body weight and composition in rats. In addition, antioxidant capacity has been evaluated by measuring malondialdehyde (MDA) levels and antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathioneperoxidase; GSHPx) activities. Fifty-six male Wistar rats were divided into eight groups including seven rats each. A control group did not receive CT nor exercise. Another control group received 200 mg/kg CT without exercise. The other six groups of rats went through an exercise regimen consisting of a 5-day training period with incremental exercise capacity, which was followed by 6 weeks of the run at 25 m/min for 45 min every day. CT was supplemented at 0, 25, 50, 100, 200, and 400 mg/kg per day during the 6 weeks. Rats submitted to exercise and supplemented with CT had a significant and dose-dependent increase in time to exhaustion and this effect seems to be independent of exercise (p < 0.05). Additionally, recovery and fatigue were improved, as shown by a significant and dose-dependent decrease in myoglobin and lactic acid plasma levels, which are two markers of muscle recovery. CT supplementation led to a dose-response decrease in body weight and visceral fat. These effects become significant at 200 and 400 mg/kg doses (p < 0.05). Additionally, the antioxidant capacity was improved, as shown by a significant and dose-dependent increase in SOD, CAT, and GSHPx. Serum MDA concentrations decreased in exercising rats with CT supplementation. CT supplementation led to a decrease in serum glucose, triglycerides, and total cholesterol concentrations with the lowest levels observed at 400 mg/kg dose (p < 0.05). These effects correlated with a significant dose-dependent increase in serum total L-carnitine, free L-carnitine, and acetyl-carnitine, which linked the observed efficacy to CT supplementation. These results demonstrate that CT supplementation during exercise provides benefits on exercise performance, recovery, and fatigue as well as improved the lipid profile and antioxidant capacity. The lowest dose leads to some of these effects seen in rats where 25 mg/kg corresponds to 250 mg/day as a human equivalent.

SUN-548 Ketone Bodies in Critical Illness Alter Cholesterol Synthesis in Skeletal Muscle, Interlinked with Protection Against Weakness

Background: Critically ill patients often develop muscle weakness, which hampers recovery. In septic mice, supplementing parenteral nutrition (PN) with ketone body 3-hydroxybutyrate (3HB) attenuated muscle weakness, but also normalized sepsis-induced low cholesterol1. As 3HB can be metabolized into cholesterol, we hypothesized that improved muscle function with 3HB was related to altered cholesterol metabolism. Methods: In a catheterized, fluid-resuscitated, antibiotics-treated mouse model of prolonged sepsis (cecal ligation and puncture), septic mice received PN supplemented with either D,L-3HB sodium salt (PN+3HB; 150 mg/day) or isocaloric glucose (PN+gluc) and healthy pair-fed mice served as controls (n=15-17 mice/group). After 5 days, ex vivo muscle force and markers of cholesterol metabolism were assessed. In 600 weak and non-weak human critically ill patients (weakness assessed on day 8±1 in ICU by MRC sum score), serum total cholesterol concentration was measured on ICU day 3 or last day for shorter stayers. Results: In mice, PN+3HB counteracted the sepsis-induced lowering of plasma cholesterol (p=0.04), which correlated positively with absolute muscle force (R2=0.19, p=0.002). Plasma mevalonate concentration, a surrogate marker of cholesterol synthesis, was reduced by sepsis (p=0.03 vs. controls), but normalized by PN+3HB (p=0.001 vs. PN+gluc). Skeletal muscle expression of cholesterol synthesis genes Srebf2, Hmgcr and Hmgcs1 was higher in PN+3HB than in PN+gluc septic mice (p≤0.01). Expression of cholesterol uptake receptor Ldlr was also increased in PN+3HB septic mice (p=0.02 vs. PN+gluc), whereas PN+3HB did not affect cholesterol efflux transporters. In contrast, PN+3HB did not alter sepsis-induced alterations in markers of hepatic cholesterol metabolism. Plasma concentration of ubiquinone, a central co-factor of the mitochondrial respiratory chain derived from mevalonate, was increased by sepsis, irrespective of PN+3HB (p<0.0001 vs. controls) and PN+3HB could not counteract sepsis-induced muscular mitochondrial dysfunction (p≤0.0009 vs. controls). This excludes the involvement of ubiquinone in muscle weakness attenuation by 3HB supplementation. However, higher muscular Nceh1 expression was observed with PN+3HB (p≤0.04 vs. controls and PN+gluc), suggesting enhanced shuttling of newly formed free cholesterol to the membranes. In human ICU patients, lower serum cholesterol concentration was observed in weak vs. non-weak patients (p=0.0002). In a multivariate model adjusted for baseline risk factors, low serum cholesterol concentrations were independently associated with muscle weakness (p=0.05). Conclusion: 3HB supplementation of PN enhanced muscle cholesterol synthesis and increased plasma cholesterol, which appeared to independently protect against sepsis-induced muscle weakness. 1 Goossens et al. (2019). Crit Care. 23: 236.

Swimming exercise activates aortic autophagy and limits atherosclerosis in ApoE−/− mice

BackgroundThe aim of this study was to investigate the beneficial effect of swimming exercise on autophagy and atherosclerosis in mice aorta, so as to clarify the possible causal relationship between autophagy activation and atherosclerosis. MethodsThe body weight was monitored regularly. Hematoxylin-eosin staining and Oil Red O staining was conducted to observe vascular morphology and plaque burden respectively. The levels of serum total cholesterol (TC), triglyceride (TG), soluble intercellular adhesion molecule-1 (sICAM-1), matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6) was examined via Enzyme-linked immu-nosorbent assays (ELISA). The mRNA expression level of autophagy markers, including LC3 and Beclin-1, was examined by real-time quantitative polymerase chain reaction (RT-PCR). The expressions of LC3-II/LC3-I and Beclin-1 are detected by Western blotting and immunohistochemistry. ResultsCompared with the model group, long-term swimming exercise decreased the weight gain of ApoE−/− mice, improved the structural disorder of artery, reduced the load of atherosclerotic lesion, and attenuated the concentrations of serum TC, TG, sICAM-1, MMP-9, and IL-6. In addition, the expression of autophagy markers LC3 and Beclin-1 increased significantly at the mRNA and protein levels. ConclusionLong-term swimming exercise could activate the autophagy and reduce atherosclerotic lesion in the aorta of ApoE−/− mice. Autophagy activation may be one of the mechanisms by which atherosclerosis is improved through exercise.

Development of omega-3 rich eggs through dietary flaxseed and bio-evaluation in metabolic syndrome.

An egg is a nutrient‐dense food that contains protein, fats, vitamins, and minerals. It is proven that the consumption of eggs influences serum lipid concentration. Therefore, a study was conducted to investigate the effect of normal and omega‐3 eggs on serum lipids profiles. Lipids were extracted from egg yolks and analyzed for fatty acids content. The present research is a crossover study design in which 20 participants were recruited randomly, and all subjects received three treatments: no eggs, omega‐3 eggs, and normal eggs. However, fasting blood was drawn at baseline and the end of each diet period and analyzed for serum lipids, blood glucose, and insulin level. Omega‐3 egg treatment showed reduction in the serum total cholesterol by 16.57 mg/dl (p < .001), triglyceride by 17.48 mg/dl, and increase in HDL cholesterol concentration by 0.48 mg/dl (p < .001) as compared to no‐egg. A significant (p < .05) reduction in blood pressure by 8.34/8.67 mm/Hg and insulin level was observed due to omega‐3 egg consumption which indicates that omega‐3 fatty acids improve insulin sensitivity. On the other hand, regular egg intake elevates serum total cholesterol and triglycerides concentration but decreases blood pressure. It was concluded that omega‐3‐enriched egg consumption had a positive effect on the serum lipid profile and blood pressure of patients with metabolic syndrome as compared to normal eggs.

Effect of High Fructose-Induced Metabolic Syndrome on Tissue Vitamin E and Lipid Peroxide Levels in Rats.

In the present study, we examined the effect of high fructose-induced metabolic syndrome (MetS) on tissue vitamin E and lipid peroxide (LPO) levels in rats. Feeding of a diet containing 60% fructose (HFD) to Wistar rats for 2, 4, and 6 wk caused week-dependent increases in HOMA-IR score and serum insulin, triglyceride, total cholesterol, and free fatty acid concentrations. Each week HFD feeding increased serum vitamin E concentration. Six-week HFD feeding reduced vitamin E status (the serum ratio of vitamin E/triglyceride+total cholesterol). Four- and 6-wk HFD feeding increased serum LPO concentration. Two-week HFD feeding increased liver, heart, kidney, and skeletal muscle (SM) vitamin E contents and decreased white adipose tissue (WAT) vitamin E content. Four- and 6-wk HFD feeding further reduced WAT vitamin E content without affecting the increased kidney and SM vitamin E contents. Six-week HFD feeding reduced the increased liver and heart vitamin E contents below the level of non-HFD feeding. Four-week HFD feeding increased heart and WAT LPO contents. Six-week HFD feeding increased liver LPO content and further increased heart and WAT LPO contents. Kidney and SM LPO contents remained unchanged. These results indicate that HFD-rats with early MetS have increased liver, kidney, heart, and SM vitamin E contents and decreased WAT vitamin E content under unchanged tissue LPO content and vitamin E status, while HFD-fed rats with progressed MetS have both decreased liver, heart, and WAT vitamin E contents under increased tissue LPO content and disrupted vitamin E status.