Decreased Serum Triglyceride Research Articles

Effect of sour tea supplementation on liver enzymes, lipid profile, blood pressure, and antioxidant status in patients with non-alcoholic fatty liver disease: A double-blind randomized controlled clinical trial.

The aim of this study was to evaluate the efficacy of sour tea supplementation in patients with nonalcoholic fatty liver disease (NAFLD). Seventy NAFLD patients were enrolled in this randomized, double-blind, placebo-controlled clinical trial. Participants received sour tea in the form of a 450 mg capsule or a placebo capsule daily for 8 weeks. Anthropometric indices, liver enzymes, lipid profile, blood pressure, and antioxidant status were evaluated at the baseline and at the end of the study. Sixty-one participants completed the study. After 8 weeks, sour tea administration significantly decreased serum triglyceride (TG) (p = .03), alanine aminotransferase (ALT) (p = .01), and aspartate aminotransferase (AST) (p = .004) levels compared with the placebo. In addition, sour tea supplementation resulted in a significant reduction in systolic blood pressure (SBP) (p = .03) and diastolic blood pressure (DBP) (p = .04), and a significant increase in serum total antioxidant capacity (TAC) levels (p ˂ .001) compared with the placebo. However, no significant changes in anthropometric measures, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) levels were observed after sour tea supplementation compared with the placebo (p > .05). Sour tea supplementation may be effective in improving serum TG, liver enzymes, and blood pressure in patients diagnosed with NAFLD. Further studies are needed to address the exact mechanism of action of these effects.

Pregabalin induced reproductive toxicity and body weight changes by affecting caspase3 and leptin expression: Protective role of wheat germ oil

Pregabalin (PGB) drug abuse is common among the youth. It substituted tramadol before its recent schedule as a controlled drug since April 2019. PGB is an antiepileptic drug acting on the central nervous system. It blocks calcium channels regulating the action of neurotransmitters and causing prolonged depolarization. The present study aimed to investigate the toxic effect of long term pregabalin abuse on the reproductive function and body weight in both male and female albino rats and to evaluate the ameliorative effect of wheat germ oil (WGO). Forty-eight rats were randomly divided into eight groups. The first four groups were males and they were treated as follows: control group (1.5 mL saline), WGO group (1.5 mL L/kg), PGB group (300 mg/kg), and protective group (PGB + WGO). All doses were administrated once per day for 60 days by gastric gavage. The second four groups were females. They were divided and treated the same as the male groups. Pregabalin caused significant weight loss, decreased serum triglyceride level, and increased leptin gene expression in all rats. PGB affected male rats reproduction by decreasing total testosterone serum level and inhibiting spermatogenesis. Reproductive toxicity in females was caused by decreasing pituitary steroids, increasing gonadal hormones, and increasing the number of atretic ovarian follicles. Mechanism of toxicity may be attributed to the PGB oxidative stress effect that induced apoptosis and caused diffuse gonadal atrophy. WGO showed a protective effect on PGB induced toxicity as all measured parameters were relatively improved.

The Role of Vitamin D Supplementation in the Treatment of Primary Hypertension: A Double-Blinded Randomized Placebo-Controlled Clinical Trial

Background: Hypertension is one of the most serious global concerns since it has affected over 1.2 billion people. Objectives: The present study aimed to determine the effect of vitamin D supplementation on blood pressure, fasting blood sugar, and lipid profile in hypertensive patients with vitamin D deficiency. Methods: In this double-blinded randomized placebo-controlled clinical trial study, 116 hypertensive patients (intervention and placebo groups, 58 each) with vitamin D deficiency (< 30 ng/mL with ECL) for 14 weeks, started from the beginning of autumn 2019 in Seyed-al-Shohada Educational Hospital in Urmia City. Fifty-five patients (49%) were male with the mean vitamin D 15.89 ± 5.09 ng/mL and 57 females with 17.29 ± 6.31 ng/mL. In a stratified blocked randomization scheme, the patients were randomly allocated into similar sized intervention and control groups based on body mass index (BMI), then the randomization with four block size was performed in each of strata by random allocation software. The intervention group received six doses of 50,000 IU vitamin D supplements for 6 weeks, then two supplements for two following months (one capsule per month). Blood pressure (24/h blood pressure measured by an ambulatory blood pressure monitoring device), vitamin D, FBS, and lipid profile (HDL, LDL, CL, and TG) were all measured at baseline and end of the study. Physical activity (measured by short IPAQ questionnaire), sun exposure using a questionnaire, dietary intake of vitamin D using three 24-hour recalls during the intervention, and anthropometric indices were measured at baseline, middle, and end of the study. Fifty-six patients in each group completed the study. The study was approved by the Ethics Committee of the Urmia University of Medical Sciences (ethics code: IR.UMSU.REC.1398.192). Results: The office blood pressure, 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP), nighttime SBP and DBP were significantly reduced in the intervention group compared to the control group, whereas the reduction of daytime SBP and DBP was not statistically significant. Vitamin D supplementation significantly decreased serum triglyceride, cholesterol, and LDL levels. Conclusions: Vitamin D supplementation had positive effects on blood pressure, triglyceride, cholesterol, and LDL levels in patients with low serum vitamin D.

Gemfibrozil Induces Anemia, Leukopenia and Reduces Hematopoietic Stem Cells via PPAR-α in Mice.

Hypercholesterolemia, also called high cholesterol, is a form of hyperlipidemia, which may be a consequence of diet, obesity or diabetes. In addition, increased levels of low-density lipoprotein (LDL) and reduced levels of high-density lipoprotein (HDL) cholesterol are associated with a higher risk of atherosclerosis and coronary heart disease. Thus, controlling cholesterol levels is commonly necessary, and fibrates have been used as lipid-lowering drugs. Gemfibrozil is a fibrate that acts via peroxisome proliferator-activated receptor alpha to promote changes in lipid metabolism and decrease serum triglyceride levels. However, anemia and leukopenia are known side effects of gemfibrozil. Considering that gemfibrozil may lead to anemia and that gemfibrozil acts via peroxisome proliferator-activated receptor alpha, we treated wild-type and peroxisome proliferator-activated receptor alpha-knockout mice with gemfibrozil for four consecutive days. Gemfibrozil treatment led to anemia seven days after the first administration of the drug; we found reduced levels of hemoglobin, as well as red blood cells, white blood cells and a reduced percentage of hematocrits. PPAR-alpha-knockout mice were capable of reversing all of those reduced parameters induced by gemfibrozil treatment. Erythropoietin levels were increased in the serum of gemfibrozil-treated animals, and we also observed an increased expression of hypoxia-inducible factor-2 alpha (HIF-2α) and erythropoietin in renal tissue, while PPAR-alpha knockout mice treated with gemfibrozil did not present increased levels of serum erythropoietin or tissue HIF-2α and erythropoietin mRNA levels in the kidneys. We analyzed bone marrow and found that gemfibrozil reduced erythrocytes and hematopoietic stem cells in wild-type mice but not in PPAR-alpha-knockout mice, while increased colony-forming units were observed only in wild-type mice treated with gemfibrozil. Here, we show for the first time that gemfibrozil treatment leads to anemia and leukopenia via peroxisome proliferator-activated receptor alpha in mice.

Hypolipemic effects of histamine is due to inhibition of VLDL secretion from the liver: involvement of both H1 and H2-receptors

The research was performed to study the mechanism whereby histamine affects the profile of plasma lipids. Six groups of ten male rats were received two injections with histamine or its H1- and H2-agonists and antagonists. Histamine caused a significant decrease in the concentrations of triglyceride, total cholesterol, and LDLc, while HDLc had no significant change. The rate of VLDL secretion was 263.6 ± 25.8 mg/h dL in control rats and was inhibited by about 68% in histamine injected rats. These changes have been mimicked by either histamine H1- or H2-agonists. The effects of H1- and H2-agonists were abolished in the presence of cetirizine and famotidine respectively. Histamine causes a significant decrease in serum triglyceride, total, and LDL-cholesterol by both H1 and H2-receptors. The decrease in serum lipids is due to the inhibitory effect of histamine or its agonists on VLDL secretion from the liver.

583-P: Effects and Safety of Pemafibrate, a Novel Hypolipidemic Agent in Japanese Type 2 Diabetes Patients Receiving Statins

The combination therapy of statins and fibrates may increase the risk of hepatic dysfunction and myopathy, so this combination was contraindicated in patients with renal impairment and required careful administration even for patients with normal renal function. However, in Japan, patients with renal impairment were excluded from the relative contraindication category in 2018. In the present study, we additionally administered 0.2 mg/day pemafibrate (PFB), a novel fibrate, for 6 months to 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and examined the efficacy and safety of the combination therapy in comparison with a PFB monotherapy group. In the combination group, a significant decrease in serum total cholesterol level was observed after 6 months of PFB treatment compared to baseline, along with increase in HDL-cholesterol. A significant decrease in serum triglyceride and a significant increase in HbA1c were observed in both groups. Significant decreases in serum creatinine kinase, which is an indicator of myopathy, and serum γ-GTP, a parameter of hepatic dysfunction, were observed in the combination group. These results demonstrated that the statin-PFB combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy. Disclosure M. Kusunoki: Other Relationship; Self; Kaken Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd. D. Sato: None. T. Sakazaki: None. Y. Natsume: None. T. Miyata: None.

179-OR: Mitochondrially Targeted Tamoxifen Improves Diet-Induced Obesity and Diabetes and Reduces Adipose Tissue Senescence in Experimental Mice

Diabetes and ageing are mutually linked and senescent cells might be involved in the development of obesity and type 2 diabetes mellitus (T2DM). Recent studies have shown that senolytic agents may improve diabetes-related pathologies. To this end we have tested our novel anti-cancer agent with senolytic properties, mitochondrially targeted tamoxifen (MitoTam), in a mouse model of T2DM. Obesity and diabetic metabolic profile were induced by high fat diet (HFD) feeding in 20 C57BL/6J male mice for 6 months with another group fed a standard diet (SD) serving as controls. Subsequently, both groups were divided into 2 subgroups (n=10 each) treated either with MitoTam (2µg/1g of body weight dissolved in 4% ethanol in corn oil) or the excipient given i.p. twice a week for a period of 4 weeks. In HFD animals, MitoTam decreased body weight already after 2 weeks of treatment, with most pronounced reduction of visceral adipose tissue (VAT, P<0.001), whereas it had no effect on body weight in SD group. MitoTam also reduced fasting glucose (P<0.001) as well as postprandial glucose AUC (P<0.001) of HFD mice to levels comparable with SD group. This glucose-lowering effect was accompanied by a decrease in serum triglycerides (P<0.002), insulin (P<0.002), leptin (P<0.001) and glucose-dependent insulinotropic peptide (GIP, P<0.03) together with reduction of mRNA expression of leptin in epididymal adipose tissue (EAT, P<0.001), EAT adipocyte size and lipid accumulation in the liver (P<0.002). HFD-induced obesity and T2DM phenotype was associated with elevated levels of senescent markers p16 and β-gal in EAT (P<0.001 for p16 and P<0.03 for β-gal vs. SD), both of which were markedly reduced by MitoTam treatment (P<0.001 for p16 and P<0.002 for β-gal vs. HFD). In conclusion, our results suggest that MitoTam significantly improves HFD-induced obesity and diabetes in mice and that this effect might be in part mediated by alleviated senescence in adipose tissue. Disclosure J. Trnovska: None. E. Davidova: None. P. Svoboda: None. H. Kratochvilova: None. M. Mraz: None. S. Hubackova: None. J. Neuzil: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. Funding Institute for Clinical and Experimental Medicine (00023001); Czech Science Foundation (GA 18-02550S)

Effect of Deglycosylated Rutin by Acid Hydrolysis on Obesity and Hyperlipidemia in High-Fat Diet-Induced Obese Mice.

The present study evaluated the effects of acid-treated rutin on hyperlipidemia and obesity in high-fat diet (HFD)-induced obese mice. The mice consumed a HFD with or without acid-treated rutin for 7 weeks. Body weight gain considerably decreased, by approximately 33%, in the acid-treated rutin (AR) and quercetin (Q) groups compared to that in the HFD group. The adipocytes’ size in epididymal fat in AR and Q groups was significantly reduced compared to that in the HFD group (p < 0.05). Treatment with AR decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the HFD group. In particular, administration of AR significantly decreased serum triglyceride (36.82 mg/dL) by 46% compared to HFD (69.30 mg/dL). The AR group also showed significantly decreased atherogenic indices and cardiac risk factors. These results suggest that deglycosylated rutin generated by acid treatment enhances the anti-obesity and hypolipidemic effects in obese mice, and provides valuable information for improving the functional properties of glycosidic flavonoids.

A comparative assessment of safety and tolerability of metoprolol versus carvedilol in patients of chronic stable angina

Background: Angina pectoris is a clinical manifestation characterized by chest pain typically in substerum radiating to left arm, jaw, back lasting for 1-5 minutes and is relieved by rest. Beta blockers are one of the drugs indicated in angina. The aim of the study is to compare safety and tolerability of metoprolol and carvedilol in patients of chronic stable angina.Methods: The study done is randomized, open label, parallel type where tablet carvedilol and tab metoprolol is given in a group of 50 patients each. The patients were followed thereafter on 8th, 16th, 24th week to study safety in terms of haematological parameters like complete blood count, liver function tests, renal function tests, serum sodium, serum potassium, fasting blood glucose, 2 hours post prandial blood glucose, HbA1C, and Lipid profile and tolerability in terms of side effects. The study was conducted for one year and the data was assessed by relevant statistical analysis where p value &lt;0.05 was considered significant.Results: It was seen that the disease was most common in the age group of 51-60 years with male preponderance, and carvedilol was found to cause non-significant decrease in Serum Triglyceride with no change in total cholesterol, HDL-C, LDL-C was found. No significant changes were observed in metoprolol group. There was no significant difference observed when blood sugar profile and other haematological parameters were considered. Both drugs were considered to be equally tolerable.Conclusions: Compared with carvedilol and metoprolol in patients of chronic stable angina, carvedilol resulted in better lipid profile whereas metoprolol showed no changes in lipid parameters.

Effects of Cacao By-Products and a Modest Weight Loss Intervention on the Concentration of Serum Triglycerides in Overweight Subjects: Proof of Concept.

Therapeutic approaches to decrease serum triglyceride (TG) concentrations are not successful mainly due to poor adherence or adverse effects of therapies. In consequence, the search for new low-cost and safer therapeutic alternatives is mandatory. Dark chocolate and cacao have shown promising results improving lipid profiles. Recently, using cacao by-products to reduce elevated cardiometabolic risk markers in an animal model of obesity induced by a high-fat diet and fructose, we showed that TGs, low-density lipoprotein cholesterol, and the TG/high-density lipoprotein (HDL) ratio decreased, suggesting that cacao by-products improved the metabolic function of obese animals. Based on these results, as a proof of concept, a blinded placebo-controlled study was implemented to explore the effects of cacao by-products on anthropometric and biochemical variables in a group of overweight subjects participating in a program composed of reduced-calorie-diet counseling plus a simple aerobic exercise plan. The results showed that counseling induced weight and abdominal circumference reductions in both groups. TGs did not change in the control group; however, TG decreased significantly by 54.9 mg/dL (27.9%) in the experimental group. The TG/HDL cholesterol ratio changed markedly (1.5) in the experimental group. The results reported suggest the use of cacao by-products as an alternative for the treatment of hypertriglyceridemia.

Physiological activity of Aloe vera in pacu (Piaractus mesopotamicus) inoculated with Aeromonas hydrophila.

Aloe vera is a traditional medicinal plant; however, its use in fish is fairly recent. We evaluated the effects of dietary A. vera on stress, innate immunity, and energy metabolism in pacu inoculated with Aeromonas hydrophila. For 7days, 192 fish were fed with diets supplemented with 0% (control), 0.5%, 1.0%, and 2.0% of the plant extract and then inoculated with bacteria and sampled 3, 6, and 24h later. All concentrations of A. vera reduced basal levels of cortisol, and 1.0% reduced cortisol levels more intensely 3h after inoculation. A. vera increased the basal respiratory activity of leukocytes/RAL (0.5 and 1.0%), increased the serum levels of lysozyme (1.0 and 2.0%) 6h after inoculation, and increased the activity of the complement system after 3h. Spleen somatic index/SSI increased with 1.0 and 2.0% A. vera. A. vera also promoted metabolic effects. It increased basal levels of lipids in the liver and muscle, as well as hepatosomatic index (1.0%) and, 3h after inoculation, prevented the reduction of serum triglyceride (1.0%) and reduced the mesenteric fat (1.0%). Bacterial inoculation increased RAL from 3 to 24h and lysozyme levels at 24h, increased serum cholesterol at 24h, and decreased serum triglyceride from 3 to 24h, regardless of A. vera. We concluded that A. vera offered for only 7days had stress-reducing effects, stimulated innate immunity, protected triglyceride levels in blood, lipid depots in the liver and muscle, and directed the energy mobilization to visceral depots.

High-Dose Dexamethasone Manipulates the Tumor Microenvironment and Internal Metabolic Pathways in Anti-Tumor Progression.

High-dose dexamethasone (DEX) is used to treat chemotherapy-induced nausea and vomiting or to control immunotherapy-related autoimmune diseases in clinical practice. However, the underlying mechanisms of high-dose DEX in tumor progression remain unaddressed. Therefore, we explored the effects of high-dose DEX on tumor progression and the potential mechanisms of its anti-tumor function using immunohistochemistry, histological examination, real-time quantitative PCR (qPCR), and Western blotting. Tumor volume, blood vessel invasion, and levels of the cell proliferation markers Ki67 and c-Myc and the anti-apoptotic marker Bcl2 decreased in response to high-dose DEX. However, the cell apoptosis marker cleaved caspase 3 increased significantly in mice treated with 50 mg/kg DEX compared with controls. Some genes associated with immune responses were significantly downregulated following treatment with 50 mg/kg DEX e.g., Cxcl9, Cxcl10, Cd3e, Gzmb, Ifng, Foxp3, S100a9, Arg1, and Mrc1. In contrast, the M1-like tumor-associated macrophages (TAMs) activation marker Nos2 was shown to be increased. Moreover, the expression of peroxisome proliferator-activated receptors α and γ (Pparα and Pparg, respectively) was shown to be significantly upregulated in livers or tumors treated with DEX. However, high-dose DEX treatment decreased the expression of glucose and lipid metabolic pathway-related genes such as glycolysis-associated genes (Glut1, Hk2, Pgk1, Idh3a), triglyceride (TG) synthesis genes (Gpam, Agpat2, Dgat1), exogenous free fatty acid (FFA) uptake-related genes (Fabp1, Slc27a4, and CD36), and fatty acid oxidation (FAO) genes (Acadm, Acaa1, Cpt1a, Pnpla2). In addition, increased serum glucose and decreased serum TG and non-esterified fatty acid (NEFA) were observed in DEX treated-xenografted tumor mice. These findings indicate that high-dose DEX-inhibited tumor progression is a complicated process, not only activated by M1-like TAMs, but also decreased by the uptake and consumption of glucose and lipids that block the raw material and energy supply of cancer cells. Activated M1-like TAMs and inefficient glucose and lipid metabolism delayed tumor cell growth and promoted apoptosis. These findings have important implications for the application of DEX combined with drugs that target key metabolism pathways for tumor therapy in clinical practice.

A Combination of Korean Red Ginseng Extract and Glycyrrhiza glabra L. Extract Enhances Their Individual Anti-Obesity Properties in 3T3-L1 Adipocytes and C57BL/6J Obese Mice.

Anti-obesity activities of Korean red ginseng saponin fraction (RGS) and/or Glycyrrhiza glabra L. extract (GG) were investigated in 3T3-L1 adipocytes and high-fat diet-induced C57BL/6J obese mice. RGS and GG extracts were mixed at a mass ratio of 3:1 (SG31), 1:1 (SG11), or 1:3 (SG13). SG31 showed the highest anti-obesity activity among the three different mass ratios of RGS and GG extracts. SG31 showed higher inhibition efficiency on triglyceride (TG) accumulation than either single extract in 3T3-L1 adipocytes and without any cytotoxicity. It also decreases the expression of adipogenic and lipogenic genes such as C/EBPα and SREBP-1c (sterol regulatory element-binding protein 1c). In the obese induced mouse model, SG31 significantly reduced white adipose tissue weight and body weight, attenuated dyslipidemia, and decreased serum TG levels. In some indices, the activity of SG31 was even higher compared with Garcinia Cambogia water extract, a positive control. The possible mechanism by which SG31 causes the above results was by activating the AMP-activated protein kinase (AMPK) pathway and stimulating the secretion of adiponectin in adipose tissue to regulate energy metabolism balance, inhibit TG formation, and promote β-oxidation of fatty acids. Therefore, SG31 may have efficacy as an anti-obesity functional food or raw material if the results can be confirmed in human studies.

Dipeptidyl peptidase-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels in patients with type 2 diabetes: A randomized controlled trial.

Type 2 diabetes and dyslipidemia are diseases that collectively increase the risk of patients developing cardiovascular complications. Several incretin-based drugs are reported to improve lipid metabolism, and one of these medications, anagliptin, is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been shown to decrease serum triglyceride and low-density lipoproteins cholesterol. This study aimed to conduct an investigation into the effects of anagliptin on serum lipid profiles. This multicenter, open-label, randomized (1:1), parallel group study was designed to evaluate the effects of anagliptin on serum lipid profiles (triglycerides, lipoproteins, apolipoproteins, and cholesterol fractions). The study involved 24 patients with type 2 diabetes at two participating hospitals for a period of 24 weeks. Patients were randomly assigned to the anagliptin (n = 12) or control (n = 12) groups. Patients in the anagliptin group were treated with 200 mg of the drug twice daily. Patients in the control group did not receive anagliptin, but continued with their previous treatment schedules. Lipid metabolism was examined under fasting conditions at baseline and 24 weeks. Patients treated with anagliptin for 24 weeks exhibited significantly reduced levels of serum apolipoprotein B-48, a marker for lipid transport from the intestine, compared with the control group patients (P < 0.05). After 24 weeks of treatment, serum adiponectin levels were significantly raised, whereas glycated hemoglobin (HbA1c) levels were significantly lower compared with the baseline in the anagliptin group (P < 0.05), but not in the control group. This study showed that the DPP-4 inhibitor anagliptin reduces fasting apolipoprotein B-48 levels, suggesting that this drug may have beneficial effects on lipid metabolism possibly mediated by the inhibition of intestinal lipid transport.

Hypoglycemic effect of glycyrrhizic acid, a natural non-carbohydrate sweetener, on streptozotocin-induced diabetic mice.

In this paper, glycyrrhizic acid (GZA) was extracted from the stem of licorice by enzymatic hydrolysis, separated and purified by silica gel column chromatography, its purity was determined by high performance liquid chromatography (HPLC), and the structure was identified by Fourier transform infrared (FT-IR) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy. The hypoglycemic activity of GZA was measured by α-glucosidase inhibition in vitro and the establishment of a T2DM diabetic mouse model in vivo. The experimental results showed that the extraction rate and purity of GZA were 92.4% and 93.53%, respectively, and the IR spectrum and NMR spectrum were consistent with the standard and literature, respectively. The IC50 value of GZA for α-glucosidase inhibition was 1.88 mmol L-1, which was close to the positive control (acarbose). In addition, GZA could reduce the fasting blood glucose of T2DM mice by increasing insulin sensitivity, increasing glucose tolerance, significantly decreasing serum triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) contents, and increasing high density lipoprotein cholesterol (HDL-C) content. At the same time, it could also repair damaged organs to some extent. Therefore, GZA has broad application prospects in the treatment of T2DM.

Ablation of Hmgb1 in Intestinal Epithelial Cells Causes Intestinal Lipid Accumulation and Reduces NASH in Mice.

Nonalcoholic steatohepatitis (NASH) is a metabolic disorder in which poor nutrition and the gut‐to‐liver interaction play a major role. We previously established that hepatic high mobility group box‐1 (HMGB1) is involved in chronic liver disease. HMGB1 increases in patients with NASH and it is expressed in intestinal epithelial cells (IEC); yet, the role of intestinal HMGB1 in the pathogenesis of NASH has not been investigated. Thus, we hypothesized that IEC‐derived HMGB1 could play a role in NASH due to local effects in the intestine that govern hepatic steatosis. Control littermates and Hmgb1 ΔIEC mice were fed for 1 or 24 weeks a control diet or a high fat, high cholesterol (CHO) and fructose‐enriched diet (HFCFD). Hepatic and intestinal injury were analyzed. Hmgb1 ΔIEC mice were protected from HFCFD‐induced NASH after 1 or 24 weeks of feeding; however, they showed extensive atypical lipid droplet accumulation and increased concentrations of triglycerides (TG) and CHO in jejunal IEC together with lower TG and other lipid classes in serum. Olive oil or CHO gavage resulted in decreased serum TG and CHO in Hmgb1 ΔIEC mice, respectively, indicating delayed and/or reduced chylomicron (CM) efflux. There was significant up‐regulation of scavenger receptor class B type 1 (SR‐B1) and down‐regulation of apolipoprotein B48 (ApoB48) proteins, suggesting decreased lipid packaging and/or CM formation that resulted in lesser hepatosteatosis. Conclusion: Ablation of Hmgb1 in IEC causes up‐regulation of SR‐B1 and down‐regulation of ApoB48, leads to lipid accumulation in jejunal IEC, decreases CM packaging and/or release, reduces serum TG, and lessens liver steatosis, therefore protecting Hmgb1 ΔIEC mice from HFCFD‐induced NASH.

Dietary supplementation with fermented moringa oleifera leaves inhibits the lipogenesis in the liver of meat ducks

The aim of this study was to compare the effects of Aspergillus niger-fermented-Moringa oleifera Lam. leaves (FMOL) and non-fermented leaf (NMOL) supplementation on growth performance, carcass quality, fat deposition, and lipometabolism for ducks. A total of 450 d-old Pekin ducks were randomly allocated into 5 dietary treatments, which were then denoted as the control group (CON, basal diet), and the NMOL group (containing 0.50% MOL in the diets), FMOL1, FMOL2 and FMOL3 groups (containing 0.25%, 0.50% and 0.75% FMOL in the diets, respectively). The results showed that, as compared with the CON, body weight gain was higher in the FMOL1 and FMOL2 groups in the period of wk 1–3, wk 4–6 and the overall period of wk 1–6, whereas feed to gain was lower in the period of wk 4–6. The dressing percentage was lower in the group FMOL3 than that of in the CON. Birds in NMOL and FMOLs had lower levels of abdominal fat and subcutaneous fat than that of the CON. The contents of hepatic lipid and triglyceride (TG) in the FMOLs groups, as well as the total cholesterol (TC) in FMOL2 and FMOL3 groups were decreased as compared with the CON or NMOL. Decreased serum TG, TC, low-density lipoprotein cholesterol and increased high-density lipoprotein cholesterol and leptin was observed in the FMOL2 and FMOL3 groups as compared with the other groups. Birds fed with FMOL2 and FMOL3 had higher serum insulin, as well as leptin-receptor transcriptional expression in comparison with the CON. Furthermore, the expression levels of lipogenesis related genes (fatty acid synthase, acetyl-CoA carboxylase, sterol-regulatory element-binding protein-1 in liver and peroxisome proliferator-activated receptor-γ) in abdominal fat were down-regulated as compared with the CON. Our results revealed that dietary 0.50% to 0.75% FMOLs alleviate body fat deposition and decease serum and hepatic lipid levels in meat ducks by suppressing lipogenesis related genes expression.

Alleviation of Tramadol-Induced Liver Toxicity in Experimental Rats by Using Kiwifruit, Turmeric Extract or Their Combination

This work was designed to study the potential effect of kiwifruit, turmeric extract or their combination in alleviation of the liver toxicity induced by tramadol intake. Thirty rats were fed on a basal diet, six of them continued on the basal diet (negative control). The remaining rats were given tramadol daily and divided into four groups, one of them served as positive control, while the other three groups were treated daily with kiwifruit juice, turmeric water extract and their combination for four weeks. The results revealed that the positive control exhibited significant decreases in serum triglycerides, total cholesterol and HDL-c levels and a significant increase in serum LDL-c as compared to the negative control. In comparing with the positive control, the serum cholesterol, triglycerides, VLDL-c and HDL-c values increased while LDL-c value decreased significantly in the three treated groups which reached the normal values of the negative control. The findings revealed significant decreases in serum levels of ALT, AST, ALP, GGT and total bilirubin and significant increases in total protein and albumin of the treated groups in comparing with the positive control. An improvement of the antioxidant parameters was observed where the serum levels of tumor necrosis factor- α, acetylcholine esterase and total oxidative capacity decreased significantly while the levels of superoxide dismutase and total antioxidants capacity increased in all the treated groups in comparing with positive control group. It is recommended by using kiwifruit and turmeric extract in the diets of those who addicted to tramadol intake.

The DNA Sequence Encoding Actin (ACT1) of Pandan (Benstonea sp.)

Triglyceride (TG) is a simple and the main lipid of the daily diet. Nowadays, TG is emerging as an independent risk factor for cardiovascular disease, and increasing clinical data that indicate a high level of this simple lipid in serum may alert and play a role in liver impairment. Red yeast rice (RYR) reduces serum TG in human and animals. The rice is widely used as a natural inhibitor of HMG-CoA reductase to correct serum cholesterol level. Bioactive components of the rice are well known to have antioxidant properties. This study examined whether RYR protects hepatocytes by evaluating the serum AST-ALT, HDL-Cholesterol (HDL-C), TG levels, and the number of liver foam cells in hypertriglyceridemic rats. Twenty male Wistar rats were grouped into 5. Four groups received a high-fat diet (HFD), 40 g/animal/day for 60 days to induce hypertriglyceridemic condition. Along with the HFD treatment, three groups received 108, 54, and 27 mg/kgBW/day of RYR, respectively. Two other groups received standard and only HFD diet, respectively. Intracardiac blood was collected for measuring AST and ALT using AST or ALT activity assay Kit, respectively, serum TG and HDL-C by Enzymatic Caloric Test. Hematoxylin-Eosin–stained 4µmm thick slices of liver tissues were prepared to count foam cell number by a light microscope with 400x magnificence. Data were analyzed using the Kruskal Wallis continued by the Mann Whitney U test. The p values of < 0.05 were considered to be significant. The present study found that 108, 54, and 27 mg/kgBW/day of RYR significantly decreased serum TG, HDL-C, AST, and ALT compared with those of hypertriglyceridemic rats receiving no RYR. The decreasing levels of the parameters were in relation to the doses of RYR. The doses of 108 and 54 mg/kgBW/day resulted in complete recovery of the liver tissues suffered from steatosis (p < 0.05). The RYR dose of 108 mg/KgBW/day completely corrects the serum HDL-C level. In conclusion, red yeast rice may have a potency to protect hepatocytes injuries due to hypertriglyceridemia.

Design, synthesis and evaluation of 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione-Based fibrates as potential hypolipidemic and hepatoprotective agents.

Six novel target compounds 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT) based fibrates were synthesized and evaluated. All the synthesized compounds were preliminarily screened by using the Triton WR-1339-induecd hyperlipidemia model, in which T1 exhibited more potent hypolipidemic property than positive drug fenofibrate (FF). T1 also significantly decreased serum triglycerides (TG), total cholesterol (TC) and low density lipoprotein cholesterin (LDL) in methionine solution (Mets) induced hyperlipidemic mice. Moreover, hepatic transaminases (AST and ALT) were obviously ameliorated after treatment with T1 and the histological observation indicated that T1 ameliorated the injury in liver tissue and inhibited the hepatic lipid accumulation. In the livers of T1-administrated rat, the levels of PPARα related to lipids metabolism were up-regulated. Additional effects such as antioxidant, anti-inflammatory and H2S releasing action confirmed and reinforced the activity of T1 as a potential multifunctional hypolipidemic and hepatoprotective agent.