scholarly journals The Influence of Hyperlipidemia on Endothelial Function of FPN1 Tek-Cre Mice and the Intervention Effect of Tetramethylpyrazine

2018 ◽  
Vol 47 (1) ◽  
pp. 119-128 ◽  
Author(s):  
Ming-Yue Sun ◽  
Miao Zhang ◽  
Shui-Ling Chen ◽  
Shu-Ping Zhang ◽  
Chun-Yu Guo ◽  
...  

Background/Aims: Systemic iron homeostasis is strictly governed in mammals; however, disordered iron metabolism (such as excess iron burden) is recognized as a risk factor for various types of diseases including AS (Atherosclerosis). The hepcidin-ferroportin axis plays the key role in regulation of iron homeostasis and modulation of this signaling could be a potential therapeutic strategy in the treatment of these diseases. TMP (Tetramethylpyrazine) has been reported to have therapeutical effect on AS. Here, we aimed to investigate the effect of iron overload under hyperlipidemia condition on the endothelial injury, inflammation and oxidative stress by employing FPN1 Tek-cre mouse model with or without TMP intervention. Methods: Subjects for this study were 80 FPN1 Tek-cre mice and 40 C57BL/6 mice and we randomly divided them into six groups: Group N: C57BL/6 mice with normal diet, Group M: C57BL/6 mice with high-fat diet, Group FN: FPN1 Tek-cre mice with normal diet, Group FNT: FPN1 Tek-cre mice with normal diet and TMP injection, Group FM: FPN1 Tek-cre mice with high-fat diet, Group FMT: FPN1 Tek-cre mice with high-fat diet and TMP injection. After seven days of treatment, blood samples were obtained to detect the levels of blood lipids, Hepcidin, NO, ET-1, ROS, MDA, SOD, IL-1, IL-6 and TNF-α respectively. The liver and aorta were used for testing the lipid deposition by using hematoxylin and eosin(HE). Results: Hyperlipidemia could cause iron overload in the aorta and increased serum hepcidin level, particularly in FPN1 Tek-cre mice, and can be reversed by TMP intervention. Knockout of Fpn1 induced increase of serum hepcidin, exacerbated endothelial dysfunction, oxidative stress and inflammatory response, particularly under hyperlipidemia condition. TMP intervention attenuated these processes. Conclusions: Our study signifies the potential application of certain natural compounds to ameliorating iron disorders induced by hyperlipidemia and protecting on endothelial function through modulation of hepcidin-ferroportin signaling.

2017 ◽  
Vol 49 (10) ◽  
pp. 793-800 ◽  
Author(s):  
Guoqiang Fan ◽  
Yu Qiao ◽  
Shixing Gao ◽  
Jun Guo ◽  
Ruqian Zhao ◽  
...  

AbstractZinc alpha2 glycoprotein (ZAG) is a new type of adipokine involved in adipose tissue mobilization, however, little is known about its lipid metabolism effect in liver. Therefore, we investigated the effects of ZAG in the regulation of hepatic lipid accumulation. Mice were randomly divided into two groups; one was fed a normal diet and another was fed a high-fat diet for eight weeks to establish obesity model. After that, the normal diet group was divided into ND (injection of pcDNA3.1) and NDZ (injection of ZAG recombinant plasmid) and the high-fat diet group was divided into HF (injection of pcDNA3.1) and HFZ (injection of ZAG recombinant plasmid). The mice were weighed once per week and injected with plasmid once every three days for eight times. The results showed that body weight and hepatic TG content were decreased dramatically in HFZ group compared with HF group. The stearoyl-CoAdesaturase1 (SCD1) and Acyl-CoA Synthetase-1 (ACSS1) protein levels in HFZ group were significantly decreased. Furthermore, phosphorylated hormone sensitive lipase (P-HSL) was significantly higher in HFZ group. In HFZ group, hepatic fatty acid translocase (CD36) and fatty acids binding protein-1 (FABP1) protein levels were reduced. In addition, the expression of phosphorylated protein kinase A (PPKA) in HFZ group was higher than the HF group. Meanwhile, NDZ group showed significantly decreased body weight and increased P-HSL level though the hepatic TG content showed no significantly changes compared with the ND group. Therefore, we conclude that ZAG may be beneficial for preventing high-fat-diet-induced hepatic lipid metabolic disorders.


2009 ◽  
Vol 118 (4) ◽  
pp. 291-301 ◽  
Author(s):  
Ahmed A. Elmarakby ◽  
John D. Imig

Obesity and hypertension are the two major risk factors that contribute to the progression of end-stage renal disease. To examine whether hypertension further exacerbates oxidative stress and vascular dysfunction and inflammation in obese rats, four groups of male Sprague–Dawley rats were fed either a normal (7% fat) or high-fat (36% fat) diet for 6 weeks and osmotic pumps were implanted to deliver ANG (angiotensin II) or vehicle for an additional 4 weeks. Treatment with the high-fat diet did not alter ANG-induced hypertension compared with the normal diet (174±6 compared with 170±5 mmHg respectively). Treatment with the high-fat diet increased body weight gain and plasma leptin levels and induced insulin resistance in normotensive and ANG-induced hypertensive rats. Plasma TBARS (thiobarbituric acid-reacting substances), a measure of oxidative stress, were elevated in high-fat diet-fed rats compared with controls (11.2±1 compared with 8.4±1 nmol/ml respectively) and was increased further in ANG-induced hypertensive rats fed a high-fat diet (18.8±2.2 nmol/ml). Urinary nitrite excretion was also decreased in rats fed a high-fat diet without or with ANG infusion compared with controls. Afferent arteriolar relaxation to acetylcholine was impaired in rats fed the high-fat diet without or with ANG infusion. Renal cortical TNF-α (tumour necrosis factor-α), COX-2 (cyclo-oxygenase-2) and phospho-IKK (inhibitor of nuclear factor κB kinase) expression increased in high-fat diet-fed rats compared with normal diet-fed rats. The increases in phospho-IKK and COX-2 expression were elevated further in ANG-induced hypertensive rats fed the high-fat diet. These results suggest that ANG-induced hypertension exacerbates oxidative stress and renal inflammation without further impairment in vascular dysfunction in high-fat diet-induced obesity.


2020 ◽  
Author(s):  
Yuan Yang ◽  
Feng Zhang ◽  
Xiao Xiao ◽  
Chunlian Ma ◽  
Hua Liu ◽  
...  

AbstractOur aims were to explore the effects of dietary and behavior interventions on lipometabolism caused by unhealthy high-fat diet and the best method to rebuild lipid homeostasis of this lifestyle. Apart from normal diet rats, 34 rats were fed with high-fat emulsion for 4 weeks before being divided into 4 groups and intervened for another 4 weeks. 8 of them were classified into high-fat control group and 9 were sorted into high-fat diet with rice vinegar group. Meanwhile, 10 were put into high-fat diet with swimming group and 7 were just for refeeding normal diet group. Then the data of body weight was recorded and analyzed. Serum, pancreas, liver, cardiac tissues and epididymis adipose were sampled as required. Indexes of serum were tested by kits. AMPKα, HNF1α, CTRP6 from tissues were detected by western blot. According to our experiments, Swimming and refeeding groups reflected a better regulation on lipid homeostasis mainly by up-regulating the expression of pancreas AMPKα. To be more specific, the refeeding rats showed lower T-CHO (P<0.001) and LDL-C (P<0.05), but higher weight gain (P<0.001),insulin level (P<0.01)and pancreas AMPKα (P<0.01)than high-fat control rats. Compared with rats experimented by swimming or rice vinegar, they showed higher weight gain (P<0.001),insulin level (P<0.01)and HNF1α, but lower of CTRP6. In summary, refeeding diet functioned better in regulating the lipometabolic level after high-fat diet. Whatever approach mentioned above we adopted to intervene, the best policy to keep the balance of lipid homeostasis is to maintain a healthy diet.


2016 ◽  
Vol 474 (1) ◽  
pp. 182-187 ◽  
Author(s):  
Xiaoyu Wang ◽  
Shiqi Zhao ◽  
Mengqi Su ◽  
Li Sun ◽  
Song Zhang ◽  
...  

Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 505
Author(s):  
Bo-Ram Choi ◽  
Dahye Yoon ◽  
Hyoung-Geun Kim ◽  
Seon Min Oh ◽  
Yung Choon Yoo ◽  
...  

The prevalence of obesity is rapidly increasing and is recognized as a serious health problem. To investigate metabolic changes in an obese model after administration of Acanthopanax sessiliflorus, mice were divided into four groups: normal diet, high-fat diet (HFD), HFD with treatment fenofibrate, and A. sessiliflorus fruit extract. The liver tissue of mice was analyzed using nuclear magnetic resonance (NMR) spectrometry-based metabolomics. In multivariate statistical analyses, the HFD group was discriminated from the normal diet group, and the group fed A. sessiliflorus fruit was discriminated from the HFD group. In biomarker analysis between the HFD group and the group fed A. sessiliflorus fruit, alanine, inosine, formate, pyroglutamate, taurine, and tyrosine, with AUC values of 0.7 or more, were found. The levels of these metabolites were distinguished from the HFD mouse model. Changes in these metabolites were confirmed to act on metabolic pathways related to antioxidant activity.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1236-1236
Author(s):  
Joohee Oh ◽  
Hyun-Sook !Kim

Abstract Objectives Cinnamon is one of the oldest spices widely used in traditional medicine and also currently used by people all around the world. Cinnamon has been known for modulating metabolic disorders by regulating insulin sensitivity. The aim of this study was to investigate the anti-obese effects of cinnamon extracts in high-fat-diet induced obese mice model. Methods After a week of adaptation period, the 6-week-old male C57BL/6J mice were randomly divided into 4 groups (n = 11 for each group) of the normal diet group (ND), the high-fat-diet group (HF), the normal diet with 1% cinnamon extracts (NC), and the high-fat diet with 1% cinnamon extracts (HC). All groups were treated for 14 weeks. Results In final body weight and body weight gain, NC group was significantly lower than ND group and HC group was significantly lower than HF group (P = 0.000). In serum TG (Triglyceride) levels and TC (Total cholesterol) levels, NC group showed significantly decreased level compared to that of ND group and HC group represented significantly decreased level compared to that of HF group (P = 0.000). Conclusions The present data showed NC group and HC group showed lower final body weight and body weight gain than ND group and HF group. Also, NC group and HC group showed the decreased level of TG (Triglyceride) and TC (Total cholesterol) compared to ND group and HF group. The further indicators of insulin-related factors are in progress. Funding Sources This study received no external funding.


2021 ◽  
Author(s):  
Ranyah Labban ◽  
Hanan fawaz ◽  
Ahmed Almnaizel ◽  
May Al-Muammar ◽  
Ramesa Bhat ◽  
...  

Abstract Background:Obesity is a risk factor for several diseases related to oxidative stress, hyperlipidemia, and hyperglycemia. Several pharmacological agents have been used to treat obesity, but these commonly exhibit undesirable side effects. The aim of this study was to explore the effects of Garcinia mangostana (mangosteen) and Curcuma longa independently and synergistically in modulating selected biochemical markers of oxidative stress, dyslipidemia, and hyperglycemia commonly observed in high-fat diet-induced obesity in rodent models. Methods:Male albino Wistar rats were divided into eight experimental groups, fed on a normal diet or high-fat diet (HFD), then given mangosteen extract (400 mg /kg body weight/day) and/or curcumin (80 mg/kg body weight/day) for 6 weeks. Oxidative stress markers, glucose, and lipid fractions were measured in the sera. Results:Curcumin was found to be more effective in reducing BMI, while mangosteen extract was found to induce a significant increase in anti-atherogenic marker HDL-C, but was ineffective in reducing dyslipidemia. Mangosteen extract and curcumin effectively reduced blood glucose. Mangosteen did not exhibit any anti-oxidative effects in normal weight rats; however, it induced a significant increase in glutathione in obese rats. Conclusion:The present study demonstrated that mangosteen pericarp extract and curcumin were independently and synergistically effective in treating obesity-induced atherogenesis.


2021 ◽  
Vol 8 (3) ◽  
pp. 179-189
Author(s):  
Anil Kumar ◽  
Anand Acharya ◽  
Subhadra Devi Velichety ◽  
Rajesh Vaderav

Diet rich in fat is one of the main risk factor for the development of Alzheimer’s disease. Studies have shown that diet rich in fat disrupts memory and learning. The present study evaluates the ameliorative role of Ginkgobiloba and Rosuvastatin against high fat diet induced neurotoxicity in CA1 (Corona Ammonis) region of hippocampus. Animals were randomly divided into six groups. Group I received normal diet, Group II received high fat diet, Group III & IV were treated with Ginkgobiloba 50mg/kg and 100mg/kg body weight, and Group V & VI were treated with Rosuvastatin 10mg/kg and 20 mg/kg body weight. All the rats were subjected to spatial learning (Morris water maze). Subsequently, rats were sacrificed and brains were removed. Golgi staining was done and CA1 neurons of hippocampus were traced using camera lucida. Dendritic branching points and dendritic intersections were quantified. Lipid profile and Super oxide (SOD) was also estimated.There was enhancement of spatial learning in treatment group rats. Furthermore, a significant increase in dendritic length and branching points was observed in CA1 region along with significant decrease in the Superoxide dismutase in rats treated with higher dose of Ginkgobiloba and Rosuvastatin. Present study concludes that Ginkgobiloba and Rosuvastatin in higher dose have protective role against high fat diet induced neurotoxicity in CA1 region.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hua Xu ◽  
Meng-bo Hu ◽  
Pei-de Bai ◽  
Wen-hui Zhu ◽  
Sheng-hua Liu ◽  
...  

Background. We aimed to examine whether proinflammatory cytokines participated in prostate cancer (PCa) development and progression promoted by high-fat diet (HFD).Methods. TRAMP (transgenic adenocarcinoma mouse prostate) mice were randomly divided into two groups: normal diet group and HFD group. Mortality rate and tumor formation rate were examined. TRAMP mice were sacrificed and sampled on the 20th, 24th, and 28th week, respectively. Levels of proinflammatory cytokines, including IL-1α, IL-1β, IL-6, and TNF-α, were tested by FlowCytomix. Prostate tissue of TRAMP mice was used for histology study.Results. A total of 13 deaths of TRAMP mice were observed, among which 3 (8.33%) were from the normal diet group and 10 (27.78%) from the HFD group. The mortality rate of TRAMP mice from HFD group was significantly higher than that of normal diet group (P=0.032). Tumor formation rate at 20th week of age of HFD group was significantly higher than that of normal diet group (P=0.045). Proinflammatory cytokines levels, including IL-1α, IL-1β, IL-6, and TNF-α, were significantly higher in HFD TRAMP mice.Conclusions. HFD could promote TRAMP mouse PCa development and progression with elevated proinflammatory cytokines levels. Proinflammatory cytokines could contribute to PCa development and progression promoted by HFD.


2007 ◽  
Vol 35 (02) ◽  
pp. 297-308 ◽  
Author(s):  
Sung Ok Kim ◽  
Su-Jin Yun ◽  
Eunjoo H. Lee

To find out whether the immunohistochemical expression of neuropeptid Y (NPY) and leptin receptor (LR) in the rat hypothalamus is influenced by adlay seed water extract (adlay), obesity in rats was induced by high fat diet (HFD) for 8 weeks; these rats were injected with 50 mg/100 g body weight adlay daily for 4 weeks. The results showed that the optical density of NPY immunoreactivity in paraventricular nucleus of rats increased approximately by 3.4 fold in HFD group compared to the normal diet group. Conversely, that of HFD + adlay group was about 2.6 fold lower than HFD group. The pattern of LR expression was similar to that of NPY. Both of NPY and LR mRNA levels, determined by real time PCR, in HFD + adlay group were decreased compared to those of HFD group, but there were no significant changes in the level of LR. These results suggest that adlay may regulate neuroendocrine activity in the brain. Accordingly, administration of adlay may be considered for therapies targeting obesity.


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