Increased Plasma Total Cholesterol Research Articles

Attenuating effect of Polygala tenuifolia Willd. seed oil on progression of MAFLD.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs). Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses. Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level. Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD.

Effects of linseed oil supplementation duration on fatty acid profile and fatty acid metabolism-related genes in the muscles of Chinese crested white ducks

Meat rich in polyunsaturated fatty acids is considered beneficial to health. Supplementing the diet with linseed oil promotes the deposition of polyunsaturated fatty acids (PUFAs) in poultry, a conclusion that has been confirmed multiple times in chicken meat. However, fewer studies have focused on the effects of dietary fatty acids on duck meat. Therefore, this study aims to evaluate the effects of the feeding time of a linseed oil diet on duck meat performance and gene expression, including meat quality performance, plasma biochemical indicators, fatty acid profile, and gene expression. For this study, we selected 168 Chinese crested ducks at 28 days old and divided them into three groups, with 56 birds in each group. The linseed oil content in the different treatment groups was as follows: the control group (0% flaxseed oil), the 14d group (2% linseed oil), and the 28d group (2% linseed oil). Ducks in the two experimental groups were fed a linseed oil diet for 28 and 14 days at 28 and 42 days of age, respectively. The results showed that linseed oil had no negative effect on duck performance (slaughter rate, breast muscle weight, and leg muscle weight) or meat quality performance (pH, meat color, drip loss, and shear force) (P > 0.05). The addition of linseed oil in the diet increased plasma total cholesterol and high-density lipoprotein cholesterol levels (P < 0.05), while decreasing triglyceride content (P < 0.05). Furthermore, the supplementation of linseed oil for four weeks affected the composition of muscle fatty acids. Specifically, levels of α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid were increased (P < 0.05), while eicosatetraenoic acid content was negatively correlated with flaxseed oil intake (P < 0.05). qRT-PCR analysis further revealed that the expression of FATP1, FABP5, and ELOVL5 genes in the breast muscle, as well as FABP3 and FADS2 genes in the thigh muscle, increased after four weeks of linseed oil supplementation (P < 0.05). However, after two weeks of feeding, CPT1A gene expression inhibited fatty acid deposition, suggesting an increase in fatty acid oxidation (P < 0.05). Overall, the four-week feeding time may be a key factor in promoting the deposition of n-3 PUFAs in duck meat. However, the limitation of this study is that it remains unknown whether longer supplementation time will continue to affect the deposition of n-3 PUFAs. Further experiments are needed to explain how prolonged feeding of linseed oil will affect the meat quality traits and fatty acid profile of duck meat.

Protective Role of Herbal Plants in Hepatotoxicity

Purpose: The liver is largest metabolic organ involved in detoxification and synthesis of essential biomolecules in the human body. Liver damage occurs due to chronic alcohol abuse, viral infections (Hepatitis A, B, C) medicines, poor hygiene, smoking, dietary substances, chemicals (Carbon tetra chloride, thioacetamide, acetaminophen, D-Galactosamine) or herb induced hepatotoxicity. The liver filters all the blood from the digestive tract, before passing it to the rest of the body to avoid the entry of toxins in the other body system and prevent severe consequences. Hepatic insufficiency may increase plasma total cholesterol and triacylglycerols with high risk of atheroscelerosis and cardiovascular disease. Free radical formation in the alcohol use result in development of hepatitis leading to cirrhosis. Plants have been used to protect liver injury by various chemicals.&#x0D; Methodology: In this study we reviewed some popular herbal plants having hepatoprotective potential.&#x0D; Findings: Polyphenols, flavonoids, terpenoids are natural antioxidants and the consumption of foods that contain these compounds in large quantities seems to play an important role in prophylaxis against many diseases.&#x0D; Unique Contribution to Theory, Practice and Policy: Herbal drugs are safe and have potential to cure hepatotoxicity. In India many plants have been identified as hepatoprotective drugs and used to treat liver disorders.

Comparison of protective effects of hesperetin and pectolinarigenin on high-fat diet-induced hyperlipidemia and hepatic steatosis in Golden Syrian hamsters.

A comparative study was conducted to determine whether hesperetin and pectolinarigenin could lower total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) in a high-fat diet (HFD)-induced high lipid model in Golden Syrian hamsters. 48 Golden Syrian hamsters (8 weeks old) were fed with a HFD for 15 days. HFD induced significant increases in plasma TC, TG, LDL, and HDL. Then, these high lipid hamsters were divided into four groups and were administered with 0.5% sodium carboxymethyl cellulose (CMC-Na), hesperetin (100 mg/kg/day), pectolinarigenin (100 mg/kg/day) or atorvastatin (1.0 mg/kg/day), for 7 weeks. It was found that pectolinarigenin treatment resulted in significant reductions in body weight, adiposity index, serum levels of TC, TG and hepatic TC, TG and free fatty acid compared to those in control hamsters with hyperlipidemia (P<0.05). However, hesperetin treatment only caused reductions in plasma TC and hepatic TG levels. Besides, the hamsters treated with pectolinarigenin showed a relatively normal hepatic architecture compared to the hepatic steatosis shown in the control group. Moreover, the expressions of fatty-acid synthase (Fasn) and solute carrier family 27 member 1 (Slc27a1) involved in lipid biosynthesis, were suppressed in the pectolinarigenin-treated groups, and the expression of carnitine palmitoyltransferase 1A (Cpt1a) involved in fatty acid oxidation was increased in the pectolinarigenin-treated group. Taken together, these results suggest pectolinarigenin exerts stronger protective effects against hyperlipidemia and hepatic steatosis than hesperetin, which may involve the inhibition of lipid uptake and biosynthesis.

Conjugated linoleic acid isomers induced dyslipidemia and lipoatrophy are exacerbated by rosiglitazone in ApoE null mice fed a Western diet

BACKGROUND: Insulin sensitizers have been used to treat Type 2 diabetes. However, their non-negligible side effects have led to cardiovascular concerns and the withdrawal of a member, rosiglitazone. OBJECTIVE: We combined conjugated linoleic acid (CLA) with rosiglitazone to test for amelioration of side effects posed by rosiglitazone in vivo. METHODS: We utilized ApoE null mice fed with Western diet (WD) to test our hypothesis. Mice were fed WD, with or without CLA administration, for 12 weeks. CLA utilized in our study consisted of a 1:1 ratio of 95% pure c9,t11, and t10,c12 isomers at a concentration of 0.1% w/v in fat-free milk. Starting from Week 12, select mice received rosiglitazone. RESULTS: It was found that mice receiving CLA from Week 0 and rosiglitazone from Week 12 had the lowest body weight and exacerbated hepatomegaly. Although these mice had attenuated insulin resistance compared to mice receiving only Western diet, they display a marked increase in total plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Mice receiving early CLA administration developed hyperleptinemia, which was not restored by rosiglitazone. CONCLUSION: Taken together, against the background of ApoE null genotype and WD feeding, simultaneous administration of 1:1 CLA and rosiglitazone led to dyslipidemic lipoatrophy.

AFM-based nanoindentation indicates an impaired cortical stiffness in the AAV-PCSK9DY atherosclerosis mouse model

Investigating atherosclerosis and endothelial dysfunction has mainly become established in genetically modified ApoE−/− or LDL-R−/− mice transgenic models. A new AAV-PCSK9DYDY mouse model with no genetic modification has now been reported as an alternative atherosclerosis model. Here, we aimed to employ this AAV-PCSK9DY mouse model to quantify the mechanical stiffness of the endothelial surface, an accepted hallmark for endothelial dysfunction and forerunner for atherosclerosis. Ten-week-old male C57BL/6 N mice were injected with AAV-PCSK9DY (0.5, 1 or 5 × 1011 VG) or saline as controls and fed with Western diet (1.25% cholesterol) for 3 months. Total cholesterol (TC) and triglycerides (TG) were measured after 6 and 12 weeks. Aortic sections were used for atomic force microscopy (AFM) measurements or histological analysis using Oil-Red-O staining. Mechanical properties of in situ endothelial cells derived from ex vivo aorta preparations were quantified using AFM-based nanoindentation. Compared to controls, an increase in plasma TC and TG and extent of atherosclerosis was demonstrated in all groups of mice in a viral load-dependent manner. Cortical stiffness of controls was 1.305 pN/nm and increased (10%) in response to viral load (≥ 0.5 × 1011 VG) and positively correlated with the aortic plaque content and plasma TC and TG. For the first time, we show changes in the mechanical properties of the endothelial surface and thus the development of endothelial dysfunction in the AAV-PCSK9DY mouse model. Our results demonstrate that this model is highly suitable and represents a good alternative to the commonly used transgenic mouse models for studying atherosclerosis and other vascular pathologies.

Abstract 438: The CETP/ApoB100 Transgenic Mouse As A Model For Metabolic Syndrome

Background: Metabolic syndrome (MetS) is a cluster of risk factors that predisposes individuals to develop atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and nonalcoholic fatty liver disease. Dyslipidemia is an essential element of MetS. Mice lack cholesterol ester transfer protein (CETP) and rapidly clear ApoB-containing lipoprotein and are resistant to the development of dyslipidemia and clinically relevant metabolic phenotypes when challenged with high fat, high cholesterol Western-type diet (WTD). We hypothesized that the presence of CETP and ApoB-containing lipoproteins would sensitize mice to the development of dyslipidemia and exacerbate metabolic phenotypes. Approach and Results: Male and female (n=7-11) C57Bl6/J mice harboring a human CETP transgene, a human ApoB100 transgene, or both transgenes were placed on a WTD (42% kCal fat, 0.2% cholesterol). Adiposity, insulin sensitivity, glucose tolerance and plasma cholesterol were assessed at the midpoint and termination of the study. Mice were anesthetized, basal bile was collected (30 min), euthanized via cardiac puncture, and tissues dissected and snap frozen. One lobe of the liver was additionally fixed for histological analysis. In both females and males, CETP/ApoB100 and ApoB100 transgenic mice showed a robust increase in total plasma cholesterol and LDL-C. The presence of CETP further increased LDL-C in ApoB100 expressing mice and modestly reduced HDL-C. Differences in body weight were not observed across genotypes. However, ApoB100 expression reduced adiposity in females, but not males. Conversely, the presence of either ApoB100 or CETP impaired insulin sensitivity in male, but not female mice. Liver histology showed increased hepatocyte ballooning in ApoB100 and CETP/ApoB100 transgenic mice, but other measures of NAFLD were unaffected. Conclusions: Mice expressing CETP/ApoB100 transgenes develop dyslipidemia more consistent with human lipoprotein profiles. The humanized lipoprotein profile reveals sexually dimorphic responses to WTD.

The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial.

A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored.

Effect of phytosterols in the treatment of hypercholesterolemia in adults – systematic review with meta-analysis / Efeitos dos fitoesteróis no tratamento da hipercolesterolemia em adultos – revisão sistemática com metanálise

Increased plasma total cholesterol (TC) and LDL-cholesterol (low-density lipoprotein) are considered risk factors for coronary disease. Phytosterols are among the dietary options for decreasing serum concentrations of TC and LDL-c by up to 15%.To evaluate the scientific evidence on the use of phytosterols in the treatment of hypercholesterolemia in adults.A systematic meta-analysis of the Medline, Embase, Web of Service, VHL, PUBMED, Scopus, Cochrane Library and LILACS databases was performed between November and December 2016. The PICO strategy was used. Inclusion criteria were randomized clinical trials with adults of both sexes using phytosterols longer than 4 weeks intervention. Exclusion criteria were animal and in vitro studies, humans less than 18 years old and individuals with other diseases (cancer, metabolic syndromes, diabetes mellitus, hypertension, renal disease, liver diseases). The risk of bias was assessed by two reviewers. The primary outcomes investigated were TC and LDL-cholesterol. Statistical analyses were conducted using the RevMan 5.3. The standardized effect size was used to estimate the standardized mean difference and 95% CI of TC and LDL-c.Twenty-seven randomized controlled trials were included in this systematic review and 26 studies in the meta-analysis of TC and LDL-cholesterol. The meta-analyzes showed an association with the reduction in plasma TC (-2.54 [-3.04; -2.03]) and LDL-c (-2.8 [-2.63; -1.53]) after intervention with the vegetable esters.The consumption of 1.5 to 2.0 g/day of phytosterols promotes reduction of TC and LDL-c in hypercholesterolemic individuals, regardless of the way they are consumed.

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson’s Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life.

Effects of lipid-lowering agents on plasma lipid profile and apolipoprotein B in patients with type 2 diabetes mellitus

Objectives: Type 2 Diabetes Mellitus (T2DM) accounts for about 90% of all cases of Diabetes Mellitus. Dyslipidaemia has been demonstrated to form a synergy with T2DM as risk factors for cardiovascular events. This study aimed to determine the plasma levels of Lipids and Apolipoprotein B-100 among Type 2 Diabetic patients, assess the effects of Lipid Lowering agents, and to study the relationship, if any, between these lipid parameters and glycemic control.Methods: One hundred and fifty participants consisting of fifty T2DM patients on a lipid-lowering agent, fifty newly diagnosed T2DM patients who are drug naïve (not on any anti-diabetic agent) and fifty apparently healthy non-diabetic controls were recruited for this study. Fasting blood samples were collected from all study participants for determination of Total Cholesterol (TC), LDL-C, Triglycerides(TG), High-Density Lipoprotein (HDL-C) and Apo B-100.&#x0D; Results: The results showed significant increases in plasma TC, LDL-C, TG and Apo B-100 with a remarkable reduction in plasma HDL-C level in the Type 2 Diabetic drug naïve group compared with the treatment and control groups. There was a significant positive correlation observed between serum Apo B-100 and level of glycaemia in the T2DM drug naïve group.Conclusion: This study further confirms the therapeutic benefits of lipid-lowering agents in reducing Apo B-100 among T2DM patients. Furthermore, maintaining good glycaemic control reduces the risk for the development of dyslipidaemia.&#x0D; Keywords: T2DM, Dyslipidaemia, Cardiovascular Diseases, Apolipoprotein B-100, Nigeria.

A review of the pharmacological effects of Anacardiaceae family on controlling lipid profile (dyslipidemia)

Dyslipidemia is a chronic non-communicable disease (CNCD), induced by abnormalities in lipid metabolism resulting from excess intake of cholesterol, trans and saturated fats. Dyslipidemia is indicated by increased plasma total cholesterol, low-density lipoprotein (LDL) and triglyceride levels, and lower high-density lipoprotein (HDL) levels. Common treatments for dyslipidemia do not indicate ideal plasma cholesterol levels for every patient, which means better treatment is required. Some species

Imatinib improves insulin resistance and inhibits injury-induced neointimal hyperplasia in high fat diet-fed mice

Imatinib, a PDGF receptor tyrosine kinase inhibitor, has been shown to suppress intimal hyperplasia in different animal models under normal metabolic milieu, diabetic, and/or hypercholesterolemic conditions. However, the impact of imatinib treatment on injury-induced neointimal hyperplasia has not yet been investigated in the setting of insulin resistance without frank diabetes. Using a mouse model of high fat diet (HFD)-induced insulin resistance and guidewire-induced arterial injury, the present study demonstrates that intraperitoneal administration of imatinib (25 mg/kg/day) for ~3 weeks resulted in a marked attenuation of neointimal hyperplasia (intima/media ratio) by ~78% (n = 6–9 per group; P < 0.05). Imatinib treatment also led to significant improvements in key metabolic parameters. In particular, imatinib improved insulin resistance and glucose tolerance, as revealed by complete inhibition of HFD-induced increase in HOMA-IR index and AUCIPGTT, respectively. In addition, imatinib treatment led to diminutions in HFD-induced increases in plasma total cholesterol and triglycerides by ~73% and ~59%, respectively. Furthermore, imatinib decreased HFD-induced increase in visceral fat accumulation by ~51% (as determined by epididymal white adipose tissue weight). Importantly, imatinib treatment in HFD-fed mice enhanced plasma levels of high-molecular-weight adiponectin by ~2-fold without affecting total adiponectin. However, there were no significant changes in mean arterial pressure in insulin-resistant state or after imatinib exposure, as measured by tail-cuff method. Together, the present findings suggest that targeting PDGF receptor tyrosine kinase using imatinib may provide a realistic treatment option to prevent injury-induced neointimal hyperplasia and diet-induced insulin resistance in obesity.

Effect of polyphenol, flavonoid, and saponin fractions from Thymus atlanticus on acute and chronic hyperlipidemia in mice

BackgroundThymus atlanticus is an endemic plant of the Mediterranean region, which has been used in the Moroccan mountain area to treat several diseases. This study aimed to investigate the effect of polyphenol, flavonoid, and saponin fractions derived from this plant on acute and chronic hyperlipidemia in male albino mice.ResultsThe results indicated that the injection of Triton WR-1339 (20 mg/100 g body weight (B.wt.)) and 6-week administration of a high-fat diet (which is an 81.8% standard diet supplemented with 2% cholesterol, 16% lard, and 0.2% cholic acid) significantly increased plasma total cholesterol, triglycerides and low-density lipoprotein cholesterol (LDL-C), but did not affect high-density lipoprotein cholesterol (HDL-C) levels in mice. Administration of a single dose (2 mg/kg B.wt.) of polyphenol, flavonoid, or saponin fractions significantly suppressed the effect of Triton injection on plasma total cholesterol, triglycerides, and LDL-C. In addition, the supplementation of the high-fat diet with polyphenol fraction (2 mg/kg B.wt./day) prevented the increase of total cholesterol, triglycerides, and LDL-C, and effectively increased HDL-C level when compared to mice feeding only the high-fat diet.ConclusionIn conclusion, phenolic compounds from Thymus atlanticus possess a significant hypocholesterolemic and hypotriglyceridemic effects and, therefore, could have an important role in the management of dyslipidemia.

INFLUENCE OF Aspergillus oryzae FERMENTED SOYBEAN MEAL ON PLASMA CHOLESTEROL AND BILE ACID LEVELS IN HYBRID TILAPIA AND POMPANO FISH

Fermentation has been suggested as an economical and effective method to eliminate anti-nutritional factors and improve the nutritional value of Defatted soybean meal (SBM). The present study aimed to examine the effects of Aspergillus oryzae fermented SBM (FSBM) on plasma cholesterol and bile acid levels in hybrid tilapia and pompano. Two isonitrogenous and isoenergetic experimental diets for each fish species were formulated with SBM and FSBM as main ingredients. The diets were denoted as SBMD (SBM-based diet) and FSBMD (FSBM-based diet). Thirty juvenile hybrid tilapia (initial body weight 55 g) and eighteen juvenile pompanos (initial body weight 61 g) were allocated to each of the 4 concrete tanks (1500-L holding capacity) and each of the 4 circular polyvinyl chloride tanks (500-L holding capacity), respectively, resulting in two replicate tanks per dietary treatment for each fish species. For 4 weeks, the fish were handfed the experimental diets to apparent satiation twice daily. The results showed that feeding FSBMD tended to increase plasma total cholesterol level, gallbladdersomatic index, anterior intestinal total bile acid level, and posterior\anterior intestinal total bile acid reduction rate compared to SBMD in both hybrid tilapia and pompano. The differences in these parameters between FSBMD and SBMD dietary groups were significant in hybrid tilapia (P &lt; 0.05), while no significant differences were found between pompano fed FSBMD and SBMD. These results indicated that fermentation of SBM with A. oryzae could effectively improve physiological conditions of hybrid tilapia fed soybean proteinbased diet and suggested that inclusion of A. oryzae FSBM might enhance growth and feed performances of the fish.

Hypoglycemic, antidyslipidemic, and antioxidant activities of methanol extract of Struchium sparganophora leaves in alloxan-induced oxidative stress-mediated diabetes in rats

BackgroundDiabetes mellitus is clinically underlined by hyperglycemia and dyslipidemia. In view of this, the current study assessed the glycemic and lipidemic control potentials of methanol extract of Sruchium sparganophora leaves (SPA) in the alloxan-induced diabetic model using male Wistar rats. Experimental diabetes was induced through a single intraperitoneal injection of 120 mg/kg freshly prepared alloxan. Thirty-six rats were randomly assigned into six groups of normoglycemic control, untreated diabetic group, and diabetic treated with (i) metformin (12 mg), (ii) metformin 12 mg + SPA 300 mg/kg, (iii) SPA 300 mg/kg, and (iv) SPA 600 mg/kg per os twice at 9.00 and 18.00 h daily for 10 days. Fasting blood glucose (FBG) level and markers of dyslipidemia, and oxidative stress markers were determined.ResultsSPA at selected doses decreased fasting blood glucose which was significantly (p < 0.05) raised by alloxan. Increase in plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) concentrations and decrease in HDL-cholesterol (HDL-C) concentration (p < 0.05) caused by alloxan were significantly moderated by SPA at selected doses. Glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities reduced by alloxan (p < 0.05) in both the liver and pancreas were reversed by SPA 300 and 600, and its combination with metformin. Decreased reduced glutathione (GSH) concentration in alloxan diabetic rats was also reversed by the extract, while the level of malondialdehyde (MDA) exacerbated by alloxan (p < 0.05) in the tissues was decreased by the extracts.ConclusionStruchium sparganophora possesses considerable antihyperglycemic, antidyslipidemic, and antioxidant potentials without compromising organ functionality.

Oral administration of trehangelin-A alleviates metabolic disorders caused by a high-fat diet through improvement of lipid metabolism and restored beneficial microbiota

The present study investigated whether or not the oral administration of trehangelin-A (THG-A) is effective for metabolic disorders caused by a high-fat diet, as we previously showed that the intraperitoneal administration of THG-A improved metabolic disorders caused by a high-fat diet. Mice received a control diet or high-fat diet for eight weeks. Concurrently, mice were orally administered 0.2 ml/mouse phosphate-buffered saline (PBS) or 1 or 10 mg/0.2 ml/mouse of THG-A once daily during the experiment. The weight gain caused by a high-fat diet was significantly suppressed by oral THG-A compared to a high-fat diet without THG-A. In addition, at eight weeks after starting the diet, the increased plasma total-cholesterol (T-CHO) and low-density lipoprotein-cholesterol (LDL-C) levels caused by a high-fat diet were significantly reduced by 10 mg/mouse THG-A and tended to attenuated by 1 mg/mouse THG-A. The LDL receptor and CYP7A1 mRNA expression in liver associated with lipid metabolism for reducing plasma LDL-C levels was significantly enhanced by oral THG-A. In contrast, oral THG-A exerted no marked effects on mice fed the control diet. The dysbiosis of a high-fat diet fed mice, which is in the form of an increased Firmicutes-to-Bacteroidetes ratio, also recovered, and the high-fat diet induced decreased levels of Bacteroides and Akkermansia genera, which are beneficial microbiota against metabolic disorders, were also restored by oral THG-A. These results indicate that oral THG-A administration acts on metabolic disorders by improving the lipid metabolism and restoring beneficial microbiota to resolve high-fat diet induced dysbiosis.

217-LB: A Novel GPR119 Agonist, DA-1241, Improves Hepatic Inflammation and Fibrosis in ob-NASH Mice

GPR119 activation is known to inhibit de novo lipogenesis in hepatocytes, but it still remains elusive if and how GPR119 agonists can affect the pathogenesis of hepatic inflammation and fibrosis in NASH. Herein, we report the therapeutic potential of DA-1241 for NASH, especially for hepatic inflammation and fibrosis. DA-1241 was given to ob/ob mice with western diet for 10 weeks. Plasma and liver tissue samples were tested for biochemical and histological analyses. Human monocyte cells and primary hepatic stellate cells were used for in vitro proof-of-concept. At the end of experiment, ob/ob NASH mice distinctly exhibited increased plasma total cholesterol and hepatic lipid accumulation, but plasma glucose and triglyceride values were within normal range. After 10-weeks of treatment, DA-1241 significantly blocked the progression of hepatic inflammation and fibrosis compared to the NASH control (-39% and -64% for NAS and fibrosis score; p&amp;lt;0.05), while MBX-2982, a GPR119 agonist under clinical development, failed to reach statistical significance at the same dose (-19.4% and -29%; p&amp;gt;0.05). Moreover, plasma total glucagon-like peptide-1 levels were increased by DA-1241 treatment, but not by MBX-2982. Plasma ALT and AST levels were significantly lower in DA-1241-treated mice, which were much lower than those of MBX-2982-treated mice. Of note, DA-1241 were more efficacious than MBX-2982 in reducing the hepatic expression of fibrotic proteins such as type 1 collagen, α-SMA, and TIMP1, and pro-inflammatory proteins including CCL2, TNFα. To explore its underlying modes of action in vitro, THP-1 macrophages or primary hepatic stellate cells were activated by LPS or TGFβ, respectively. DA-1241 inhibited the differentiation and activation of macrophages and blocked stellate cells activation. Our findings suggest that DA-1241 has a therapeutic potential for NASH, which may be partly attributed to blocking macrophage and stellate cell activation in addition to the inhibition of lipogenesis. Disclosure H. Park: Employee; Self; Dong-A ST Co., Ltd. B. Lee: Employee; Self; DONG-A ST Co,Ltd. Y. Chae: Employee; Self; Dong-A ST Co., LTD. M. Kim: Employee; Self; Dong-A ST Co., Ltd.

HDL Receptor SR-B1 Deficiency Increased Inflammatory Dyslipidemia and Adipocyte Hypertrophy and Attenuated the Hepatic Steatosis in Murine Diet-Induced Obesity

Abstract Objectives We tested whether the scavenger receptor, class B type 1 (SR-B1), a physiologically relevant HDL receptor, modulates the metabolic and inflammatory phenotype of obese mice, accompanied by changes in adipocyte and hepatocyte lipid deposits. Methods Male SR-B1 knock-out (KO) mice and wild-type (WT) littermates were fed for 12 weeks with a high-fat diet (HFD, n = 12 per group) to induce obesity. Animals were euthanized after overnight food deprivation. Blood was obtained and adipose tissue and liver were removed. Plasma or frozen tissues were used for biochemical analyses or assessed by light microscopy and immunohistochemistry. Comparisons between WT and KO mice fed with HFD were performed and differences were considered statistically significant when P &amp;lt; 0.05. Results Compared to obese WT, obese HFD-fed SR-B1 KO mice showed increased plasma total cholesterol (p &amp;lt; 0.0001) and triglycerides (TG) (p &amp;lt; 0.01) as well as tumor necrosis factor-α (TNF-α) (p &amp;lt; 0.0001) levels. Also, these animals exhibited white fat with larger adipocytes (p &amp;lt; 0.0001) and increased macrophage-based crown-like structure formation (p &amp;lt; 0.01), compared to HFD-fed WT mice, revealing a more inflammatory adipose tissue. These changes in adipose tissue were associated with reduced hepatic steatosis: reduced hepatocyte lipid droplet area (p &amp;lt; 0.0001) and decreased liver TG content (p &amp;lt; 0.0001). In addition, obese SR-B1-deficient mice showed reduced hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) expression, more efficient hepatic fatty acid β-oxidation and increased very-low-density lipoprotein (VLDL)-TG secretion compared to obese HFD-fed WT mice Furthermore, liver fatty acid (FA) composition in obese SR-B1-deficient mice revealed a reduction in monounsaturated (MUFA) (p &amp;lt; 0.01), but an increase in polyunsaturated (PUFA) (p &amp;lt; 0.05), fatty acid content, compared to obese WT mice. Conclusions Our findings demonstrate that SR-B1 expression modulates high fat feeding-associated inflammatory dyslipidemia, adipocyte hypertrophy, and hepatic steatosis; key processes underlying the pathogenesis of highly prevalent chronic diseases, such as obesity and non-alcoholic fatty liver disease (NAFLD). Funding Sources FONDECYT 1,150,399, FONDECYT 1,180,525.

The Golden Egg: Nutritional Value, Bioactivities, and Emerging Benefits for Human Health.

Egg is an encapsulated source of macro and micronutrients that meet all requirements to support embryonic development until hatching. The perfect balance and diversity in its nutrients along with its high digestibility and its affordable price has put the egg in the spotlight as a basic food for humans. However, egg still has to face many years of nutritionist recommendations aiming at restricting egg consumption to limit cardiovascular diseases incidence. Most experimental, clinical, and epidemiologic studies concluded that there was no evidence of a correlation between dietary cholesterol brought by eggs and an increase in plasma total-cholesterol. Egg remains a food product of high nutritional quality for adults including elderly people and children and is extensively consumed worldwide. In parallel, there is compelling evidence that egg also contains many and still-unexplored bioactive compounds, which may be of high interest in preventing/curing diseases. This review will give an overview of (1) the main nutritional characteristics of chicken egg, (2) emerging data related to egg bioactive compounds, and (3) some factors affecting egg composition including a comparison of nutritional value between eggs from various domestic species.