scholarly journals Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells 

2020 ◽  
Author(s):  
Liyu Zhou ◽  
Jun Long ◽  
Yuting Sun ◽  
Weikai Chen ◽  
Runze Qiu ◽  
...  

Abstract Background: Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE-/- mice and investigate the underlying mechanism.Methods: ApoE-/- mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4+ T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4+ T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4+ T cells were measured. Results: In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4+ T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4+ T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4+ T cells.Conclusion: These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE-/- mice, inhibited the proliferation and activation of CD4+ T cells and regulated the expression of Dnmt1 and Dnmt3b.

2020 ◽  
Author(s):  
Liyu Zhou ◽  
Jun Long ◽  
Yuting Sun ◽  
Weikai Chen ◽  
Runze Qiu ◽  
...  

Abstract Background Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE -/- mice and investigate the underlying mechanism. Methods ApoE -/- mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4 + T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4 + T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4 + T cells were measured. Results In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4 + T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4 + T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4 + T cells. Conclusion These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE -/- mice and inhibited the proliferation and activation of CD4 + T cells by regulating the expression of Dnmt1 and Dnmt3b.


Marine Drugs ◽  
2019 ◽  
Vol 17 (11) ◽  
pp. 637 ◽  
Author(s):  
Yuling Ding ◽  
Lei Wang ◽  
SeungTae Im ◽  
Ouibo Hwang ◽  
Hyun-Soo Kim ◽  
...  

Diphlorethohydroxycarmalol (DPHC) is one of the most abundant bioactive compounds in Ishige okamurae. The previous study suggested that DPHC possesses strong in vitro anti-obesity activity in 3T3-L1 cells. However, the in vivo anti-obesity effect of DPHC has not been determined. The current study explored the effect of DPHC on high-fat diet (HFD)-induced obesity in C57BL/6J mice. The results indicated that oral administration of DPHC (25 and 50 mg/kg/day for six weeks) significantly and dose-dependently reduced HFD-induced adiposity and body weight gain. DPHC not only decreased the levels of triglyceride, low-density lipoprotein cholesterol, leptin, and aspartate transaminase but also increased the level of high-density lipoprotein cholesterol in the serum of HFD mice. In addition, DPHC significantly reduced hepatic lipid accumulation by reduction of expression levels of the critical enzymes for lipogenesis including SREBP-1c, FABP4, and FAS. Furthermore, DPHC remarkably reduced the adipocyte size, as well as decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes including PPARγ, C/EBPα, SREBP-1c, FABP4, and FAS, which regulate the lipid metabolism in the epididymal adipose tissue (EAT). Further studies demonstrated that DPHC significantly stimulated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in both liver and EAT. These results demonstrated that DPHC effectively prevented HFD-induced obesity and suggested that DPHC could be used as a potential therapeutic agent for attenuating obesity and obesity-related diseases.


2018 ◽  
Vol 46 (01) ◽  
pp. 119-136 ◽  
Author(s):  
Sarmila Nepali ◽  
Ji-Yun Cha ◽  
Hyeon-Hui Ki ◽  
Hoon-Yeon Lee ◽  
Young-Ho Kim ◽  
...  

Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.


2020 ◽  
Vol 39 (8) ◽  
pp. 1005-1018 ◽  
Author(s):  
I Cinar ◽  
Z Halici ◽  
B Dincer ◽  
B Sirin ◽  
E Cadirci

The presence of 5-HT7r’s in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r’s, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r’s by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r’s are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Bilal A. Zargar ◽  
Mubashir H. Masoodi ◽  
Bahar Ahmed ◽  
Showkat A. Ganie

The present study was intended to evaluate the effects of Paeonia emodi rhizome extracts on serum triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), atherogenic index (AI), superoxide dismutase (SOD), and glutathione peroxidase (GPx). The plant was extensively examined for its in vitro antioxidant activity, and the preliminary phytochemical screening was carried out using standard protocols. Male Wistar rats were induced with hyperlipidemia using high-fat diet and were treated orally with hydroalcoholic and aqueous extracts at the dose of 200 mg/kg bw for 30 days. TGs, TC, LDL-c, and AI were significantly reduced while HDL-c, SOD, and GPx levels rose to a considerable extent. After subjecting to acute toxicity testing, the extracts were found to be safe. The observations suggest antihyperlipidemic and antioxidant potential of P. emodi in high-fat diet induced hyperlipidemic/oxidative stressed rats.


Author(s):  
Maria Donatella Semeraro ◽  
Gunter Almer ◽  
Melanie Kaiser ◽  
Sieglinde Zelzer ◽  
Andreas Meinitzer ◽  
...  

Abstract Purpose Regular exercise reduces obesity and the risk of cardiovascular disease. However, health-promoting benefits of physical activity are commonly associated with increased inflammation and oxidative stress. Here, we tested whether constant moderate exercise is able to prevent or attenuate the oxidative/nitrosative stress, inflammation, and serum lipids in lean and obese rats. Methods Four-month-old female Sprague Dawley rats received standard or a high-fat diet. Animals were subjected to a physical activity protocol, consisting of 30 min forced treadmill exercise for 5 consecutive days per week during 10 months. Baseline and sedentary (non-exercised) rats were used as controls. Lipids, oxidized low-density lipoprotein cholesterol, nitric oxide metabolites, and pro- and anti-inflammatory markers were measured in blood collected upon euthanasia. Results At variance to young baseline control rats, 14-month-old animals fed normal diet had increased plasma lipid levels, including total cholesterol and triglycerides, which were further elevated in rats that consumed a high-fat diet. While treadmill exercise did not lower the amount of serum lipids in standard diet group, forced physical activity reduced non-high-density lipoprotein cholesterol in response to high-fat diet feeding. Exercised rats fed standard diet or high-fat diet had lower abundancy of nitric oxide metabolites, which coincided with increased levels of oxidized low-density lipoprotein cholesterol. Accordingly, the amount of nitric oxide metabolites correlated inversely with oxidized low-density lipoprotein cholesterol and homo-arginine. Exercise significantly reduced inflammatory cytokines in high-fat diet fed rats only. Conclusion Our study suggests that regular exercise alters the equilibrium between oxidative and anti-oxidative compounds and reduces pro-inflammatory cytokines.


Author(s):  
Sihoon Park ◽  
Jae-Joon Lee ◽  
Hye-Won Shin ◽  
Sunyoon Jung ◽  
Jung-Heun Ha

Soybean koji refers to steamed soybeans inoculated with microbial species. Soybean fermentation improves the health benefits of soybeans. Obesity is a serious health concern owing to its increasing incidence rate and high association with other metabolic diseases. Therefore, we investigated the effects of soybean and soybean koji on high-fat diet-induced obesity in rats. Five-week-old male Sprague-Dawley rats were randomly divided into four groups (n = 8/group) as follows: (1) regular diet (RD), (2) high-fat diet (HFD), (3) HFD + steamed soybean (HFD+SS), and (4) HFD + soybean koji (HFD+SK). SK contained more free amino acids and unsaturated fatty acids than SS. In a rat model of obesity, SK consumption significantly alleviated the increase in weight of white adipose tissue and mRNA expression of lipogenic genes, whereas SS consumption did not. Both SS and SK reduced serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels, and increased high-density lipoprotein cholesterol levels. SS and SK also inhibited lipid accumulation in the liver and white adipose tissue and reduced adipocyte size. Although both SS and SK could alleviate HFD-induced dyslipidemia, SK has better anti-obesity effects than SS by regulating lipogenesis. Overall, SK is an excellent functional food that may prevent obesity.


2014 ◽  
Vol 92 (5) ◽  
pp. 405-417 ◽  
Author(s):  
Xian-Wei Li ◽  
Yan Liu ◽  
Wei Hao ◽  
Jie-Ren Yang

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.


2017 ◽  
Vol 43 (5) ◽  
pp. 1961-1973 ◽  
Author(s):  
Yan Bai ◽  
Zhenli Su ◽  
Hanqi Sun ◽  
Wei Zhao ◽  
Xue Chen ◽  
...  

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.


2018 ◽  
Vol 19 (12) ◽  
pp. 4023 ◽  
Author(s):  
Pengpeng Hua ◽  
Zhiying Yu ◽  
Yu Xiong ◽  
Bin Liu ◽  
Lina Zhao

Lipid metabolism disorder (LMD) is a public health issue. Spirulina platensis is a widely used natural weight-reducing agent and Spirulina platensis is a kind of protein source. In the present study, we aimed to evaluate the effect of Spirulina platensis protease hydrolyzate (SPPH) on the lipid metabolism and gut microbiota in high-fat diet (HFD)-fed rats. Our study showed that SPPH decreased the levels of triglyceride (TG), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-c), alanine transaminase (ALT), and aspartate transaminase (AST), but increased the level of high-density-lipoprotein cholesterol (HDL-c) in serum and liver. Moreover, SPPH had a hypolipidemic effect as indicated by the down-regulation of sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl CoA carboxylase (ACC), SREBP-1c, and peroxisome proliferator-activated receptor-γ (PPARγ) and the up-regulation of adenosine 5’-monophosphate (AMP)-activated protein kinase (AMPK) and peroxisome proliferator-activated receptorα (PPARα) at the mRNA level in liver. SPPH treatment enriched the abundance of beneficial bacteria. In conclusion, our study showed that SPPH might be produce glucose metabolic benefits in rats with diet-induced LMD. The mechanisms underlying the beneficial effects of SPPH on the metabolism remain to be further investigated. Collectively, the above-mentioned findings illustrate that Spirulina platensis peptides have the potential to ameliorate lipid metabolic disorders, and our data provides evidence that SPPH might be used as an adjuvant therapy and functional food in obese and diabetic individuals.


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