scholarly journals Silencing ferritin alleviates atherosclerosis in mice via regulating the expression levels of matrix metalloproteinases and interleukins

2021 ◽  
Author(s):  
Mei Zheng ◽  
Lizhuo Li ◽  
Yuqian Liu ◽  
Yun Liang ◽  
Xiaoyong Qi
Keyword(s):  
Matrix Metalloproteinases ◽  
Western Blot ◽  
Knockout Mice ◽  
Blot Analysis ◽  
High Fat Diet ◽  
Western Blot Analysis ◽  
High Fat ◽  
Expression Levels ◽  
Atherosclerotic Lesions ◽  
Apoe Knockout Mice

This study was conducted to investigate the roles of ferritin in atherosclerosis. The mouse model of atherosclerosis was established by feeding ApoE knockout mice with a high-fat diet. The mice were then treated with ferritin-overexpressing and -silencing constructs, and assessed for interleukins (ILs) and matrix metalloproteinases (MMPs) levels using ELISA and Western blot analysis. After being fed with a high-fat diet, the ApoE knockout mice developed pro-atherogenic lipid profiles with elevated total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C). They also showed increased atherosclerotic lesions including narrowed lumen diameter, reduced lumen area, and increased plaque size. Following injection of the overexpression and silencing constructs, mRNA levels of ferritin were increased and decreased, respectively, and at the same time the atherosclerotic lesions were aggravated and alleviated, respectively. Further analysis indicated that silencing of ferritin gene reduced IL-1β and IL-10 levels while overexpressing ferritin increased them. On other hand, the TNF-α levels showed an opposite trend. MMP8, MMP12 and MMP13 levels were increased or decreased significantly after the mice were injected with ferritin over-expression or silencing vectors, respectively. Western blot analysis showed that compared to the control, overexpressing ferritin resulted in increased expression of p-JNK while silencing ferritin decreased the expression. Meanwhile, the levels of pc-Jun remained unchanged. Our work demonstrates that ferritin can regulate the progress of atherosclerosis via regulating the expression levels of MMPs and interleukins. Silencing ferritin inhibits the development of atherosclerosis and is, therefore, worth being further investigated as a potential therapeutic approach for this disease.

scholarly journals Differential expression of liver proteins between obesity-prone and obesity-resistant rats in response to a high-fat diet

2011 ◽  
Vol 106 (4) ◽  
pp. 612-626 ◽  
Author(s):  
Xia Wang ◽  
Jung-Won Choi ◽  
Jeong In Joo ◽  
Dong Hyun Kim ◽  
Tae Seok Oh ◽  
...  
Keyword(s):  
Western Blot ◽  
Blot Analysis ◽  
High Fat Diet ◽  
Western Blot Analysis ◽  
Statistical Significance ◽  
Differentially Expressed ◽  
High Fat ◽  
Two Dimensional Gel Electrophoresis ◽  
Or Groups ◽  
Proteomic Study

Rodents respond to a chronic high-fat diet (HFD) in two ways: some readily become obese (obesity prone, OP) and others do not (obesity resistant, OR). Although several hypotheses have been proposed, the mechanisms underlying the inter-individual susceptibility to diet-induced obesity remain to be fully defined. In the present study, two-dimensional gel electrophoresis (2-DE) combined with matrix-assisted laser desorption ionisation time-of-flight MS was carried out for identification of differentially expressed liver proteins in OP and OR rats fed a HFD, in an attempt to discover marker proteins involved in susceptibility and/or resistance to obesity in rat liver. The 2-DE analysis demonstrated that forty spots from 380 visualised spots were differentially regulated between the groups. Among these forty spots, twelve were differentially expressed proteins between OP and OR rats, reaching statistical significance. Of these, five proteins have already been linked to obesity; however, seven proteins involved in obesity susceptibility or resistance were identified for the first time in the present study. In order to validate the proteomic results and gain insight into the metabolic changes between the OP and OR groups, we further confirmed the expression pattern of some proteins of interest by Western blot analysis. Combined results of proteomic analysis with Western blot analysis revealed that reduced lipogenesis and increased fat oxidation were achieved in the livers of OR rats. In conclusion, the present proteomic study is an important advance over the previous steps required for identification of OP and OR rats, and should prove valuable in the search for the pathogenesis of obesity in humans.

scholarly journals Exogenous IGF-1 improves cognitive function in rats with high-fat diet consumption

2020 ◽  
Vol 64 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Feng Wang ◽  
Lu Wang ◽  
Yifeng Wang ◽  
Dai Li ◽  
Tianpeng Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Western Blot ◽  
Blot Analysis ◽  
High Fat Diet ◽  
Western Blot Analysis ◽  
High Fat ◽  
Anxiety Behavior ◽  
And Oxidative Stress ◽  
Creb Pathway

Insulin-like growth factor-1 (IGF-1) improves cognitive function, but its mechanism has not been elucidated. The aim of the study was to explore whether IGF-1 exerted its protective effect on cognitive function and anxiety behavior through the activation of PI3K/Akt/CREB pathway in high-fat diet rats. Neuronal cells HT22 were treated with nothing, IGF-1, IGF-1 + LY294002 or IGF-1 + 666-15. Expressions of p-PI3K, p-Akt and p-CREB were measured using Western blot analysis. Thirty C57BL/6J rats were used. After feeding with high-fat diet, normal saline, PEG-IGF-1, PEG-IGF-1 + LY294002 or PEG-IGF-1 + 666-15 was treated. Cognitive function and anxiety behavior were assessed by Morris water maze and open field test. Several inflammation and oxidative stress biomarkers were measured using recognized methods. Expressions of p-PI3K and p-CREB were also measured using Western blot analysis. After IGF-1 treatment in cells, expressions of p-PI3K, p-Akt and p-CREB were increased. Furthermore, LY294002 downregulated the expressions of these three proteins, but 666-15 only inhibited the expression of CREB in the cells. Compared with the control rats, we found abnormalities of cognitive function and anxiety behavior, inhibition of PI3K/Akt/CREB pathway and increase of oxidative stress and inflammation in high-fat diet rats. After PEG-IGF-1 treatment, the changes in high-fat diet rats were reversed. Then, we blocked the pathway and found that these blockers attenuated the protective effects of PEG-IGF-1. In conclusion, IGF-1 improved cognitive function and anxiety behavior in high-fat diet rats and inhibited inflammation and oxidative stress in hippocampus tissue through the activation of PI3K/Akt/CREB pathway.

FO053ROLE OF KETONE BODY METABOLISM IN SGLT2 INHIBITOR-MEDIATED RENOPROTECTION IN HIGH FAT DIET-FED APOE-KNOCKOUT MICE

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Issei Tomita ◽  
Shinji Kume ◽  
Kosuke Yamahara ◽  
Mako Yasuda-Yamahara ◽  
Naoko Takeda ◽  
...  
Keyword(s):  
Knockout Mice ◽  
High Fat Diet ◽  
Ketone Body ◽  
Sglt2 Inhibitor ◽  
High Fat ◽  
Apoe Knockout Mice ◽  
Ketone Body Metabolism

scholarly journals PROTECTIVE EFFECT OF PHYLLANTHUS EMBLICA EXTRACT PREVENT CONTRAST-INDUCED ACUTE KIDNEY INJURY IN RATS

2019 ◽  
pp. 197-201
Author(s):  
SUPRANEE KONGKHAM ◽  
ADIS TASANARONG ◽  
ARUNPORN ITHARAT
Keyword(s):  
Acute Kidney Injury ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Kidney Injury ◽  
Saline Control ◽  
Phyllanthus Emblica ◽  
Rt Pcr ◽  
Expression Levels ◽  
Apoptotic Effect

Objective: The objective of the study was to investigate the anti-apoptosis effect of the extract from Phyllanthus emblica (PE) for the prevention of contrast-induced acute kidney injury (CI-AKI). Methods: Male Sprague Dawley rats were given saline (control) or PE extracts (500 mg/kg/day) for 5 days before the induction of CI-AKI. Renal tissues were collected for an evaluation of gene expression and immunohistochemistry (IHC). To indicate anti-apoptotic effect, the expression levels of Bax, Bcl-2, and caspase in kidney were also determined, using real-time polymerase chain reaction (RT-PCR) and Western blot analysis. Results: In the CI-AKI group, RT-PCR and Western blot analysis revealed that the expression levels of Bax and cleaved-caspase-3 were upregulated in the CI-AKI group, whereas the expression of Bcl-2 was downregulated. However, the pre-treatment with PE increased Bcl-2 expression. Moreover, decreased cleaved-caspases-3 activity was also detected using IHC. Conclusion: These findings suggested that pretreatment with PE extract provided the anti-apoptotic effect against CI-AKI in the rat model.

Abstract P312: The Essential Role Of Prak In Preserving Cardiac Function And Insulin Resistance In High Fat Diet-induced Diabetes

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Yu T Zhao ◽  
Jianfeng Du ◽  
Thomas J Zhao ◽  
Hao Wang ◽  
Marshall Kadin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cardiac Function ◽  
Western Blot ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Tolerance Test ◽  
Wild Type ◽  
High Fat

Background: p38 regulated/activated protein kinase (PRAK) plays a crucial role in modulating cell death and survival. However, the role of PRAK in mediating cardiac dysfunction and metabolic disorders remains unclear. We examined the effects of deletion of PRAK on modulating cardiac function and insulin resistance in mice exposed to a high fat diet (HFD). Methods: Wild type and PRAK -/- mice at 8 weeks old were exposed to either chow food or HFD for a consecutive 16 weeks. Glucose tolerance test and insulin tolerance test were employed to assess insulin resistance. Echocardiography was employed to assess myocardial function. Western blot was used to determine the molecular signaling involved in phosphorylation of IRS-1, AMPKα, ERK-44/42, and irisin. Real time-PCR was used to assess the hypertrophic genes of the myocardium. Histological analysis was employed to assess the hypertrophic response, interstitial myocardial fibrosis, and apoptosis in the heart. Results: HFD induced metabolic stress is indicated by glucose intolerance and insulin intolerance. PRAK knockout aggravated insulin resistance, as indicated by glucose intolerance and insulin intolerance testing as compared to wild type littermates. As compared to wild type, hyperglycemia and hypercholesterolemia were manifested in PRAK-knockout mice following high fat diet intervention. High fat diet intervention displayed a decline in fractional shortening (FS) and ejection fraction (EF). However, deletion of PRAK exacerbated the decline in EF and FS as compared to wild type mice following HFD treatment. In addition, PRAK knockout mice enhanced the expression of myocardial hypertrophic genes including ANP, BNP, and βMHC in HFD treatment, which was also associated with an increase in cardiomyocyte size and interstitial fibrosis. Western blot indicated that deletion of PRAK induces decreases in phosphorylation of IRS-1, AMPKα, and ERK44/42 as compared to wild type controls. Conclusion: Our finding indicates that deletion of PRAK promoted myocardial dysfunction, cardiac remodeling, and metabolic disorders in response to HFD.

scholarly journals ZINC SULPHATE REDUCES THE BODY WEIGHT OF APOE-KNOCKOUT MICE FED WITH HIGH FAT DIET

Heart ◽  
2012 ◽  
Vol 98 (Suppl 2) ◽  
pp. E117.2-E117
Author(s):  
Jiang Jin-jin ◽  
Wang Hui-feng ◽  
Jiang Jin-jin
Keyword(s):  
Body Weight ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Zinc Sulphate ◽  
The Body ◽  
High Fat ◽  
Apoe Knockout Mice
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