scholarly journals Knockout of Low Molecular Weight FGF2 Attenuates Atherosclerosis by Reducing Macrophage Infiltration and Oxidative Stress in Mice

2018 ◽  
Vol 45 (4) ◽  
pp. 1434-1443 ◽  
Author(s):  
Wenjing Liang ◽  
Qian Wang ◽  
Hui Ma ◽  
Wenjiang Yan ◽  
Jingjing Yang

Background/Aims: Fibroblast growth factor 2 (FGF2) plays a predominant role during angiogenesis in the adventitia and in atherosclerotic plaque. A dilemma exists, however, as to whether angiogenic stimulation by FGF2 for the prevention and treatment of atherogenesis is feasible. The aim of this study is to investigate the effect of the 18-kDa FGF-2 isoform on atherosclerosis progression in high-fat diet-fed apolipoprotein E knockout (ApoE-/-) mice. Methods: We established a model of atherosclerosis using ApoE and 18-kDa FGF-2 gene double knockout mice. They were randomly divided into three groups depending on the duration of diet: 8 weeks, 12 weeks and 16 weeks. Then, we studied the morphology and inflammatory factor staining in the atherosclerosis plaque of these mice. Results: Knockout of the 18-kDa FGF-2 isoform did not change the metabolic characteristics of the mice. Compared to the control group, knockout of the 18-kDa FGF-2 isoform significantly attenuated atherogenesis, reduced aortic plaques, reduced macrophage infiltration and suppressed oxidative stress in mice fed with a high fat diet at all-time points. Conclusions: 18-kDa FGF-2 aggravated the inflammatory reaction of atherosclerosis.

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


Foods ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2202
Author(s):  
Micaelle Oliveira de Luna Freire ◽  
Luciana Caroline Paulino do Nascimento ◽  
Kataryne Árabe Rimá de Oliveira ◽  
Alisson Macário de Oliveira ◽  
Thiago Henrique Napoleão ◽  
...  

High-fat diet (HFD) consumption has been linked to dyslipidemia, low-grade inflammation and oxidative stress. This study investigated the effects of a mixed formulation with Limosilactobacillusfermentum 139, L. fermentum 263 and L. fermentum 296 on cardiometabolic parameters, fecal short-chain fatty acid (SCFA) contents and biomarkers of inflammation and oxidative stress in colon and heart tissues of male rats fed an HFD. Male Wistar rats were grouped into control diet (CTL, n = 6), HFD (n = 6) and HFD with L. fermentum formulation (HFD-Lf, n = 6) groups. The L.fermentum formulation (1 × 109 CFU/mL of each strain) was administered twice a day for 4 weeks. After a 4-week follow-up, biochemical parameters, fecal SCFA, cytokines and oxidative stress variables were evaluated. HFD consumption caused hyperlipidemia, hyperglycemia, low-grade inflammation, reduced fecal acetate and propionate contents and increased biomarkers of oxidative stress in colon and heart tissues when compared to the CTL group. Rats receiving the L. fermentum formulation had reduced hyperlipidemia and hyperglycemia, but similar SCFA contents in comparison with the HFD group (p < 0.05). Rats receiving the L. fermentum formulation had increased antioxidant capacity throughout the colon and heart tissues when compared with the control group. Administration of a mixed L. fermentum formulation prevented hyperlipidemia, inflammation and oxidative stress in colon and heart tissues induced by HFD consumption.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yinji Liang ◽  
Yupei Zhang ◽  
Yuanjun Deng ◽  
Shu Liang ◽  
Yifang He ◽  
...  

We evaluate the effects of the Chaihu-Shugan-San decoction on intestinal microbe dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats that were fed a high-fat diet. Twenty-four SD rats (male, six weeks old, 200 ± 20 g) were randomly divided into three groups: normal control group (NC group), high-fat diet-fed group (HFD group), and Chaihu-Shugan-San decoction intervention group (CH group). The NC group rats were given standard feed, the HFD group rats were all fed a high-fat diet (83% standard feed + 10% lard oil + 5% sucrose + 1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus Chaihu-Shugan-San at 9.6 g•kg−1•d−1. Body composition, serum and liver lipids, inflammatory markers, intestinal microbial population, and the NLRP3 pathway-associated protein were assessed. The results showed that Chaihu-Shugan-San decoction significantly reduced body weight and total fat mass and the levels of serum LPS, TG, TNF-α, IL-1β, and IL-18, as well as liver TC, TG, TNF-α, IL-1β, and IL-18 (P <0.05). The abundance of Enterobacteriaceae (0.375% versus 0.064%,P< 0.05), Staphylococcaceae families (0.049% versus 0.016%,P< 0.05) andVeillonellagenus (0.096% versus 0.009%,P <0.01) significantly decreased, whereas the abundance ofAnaeroplasmagenus (0.0005% versus 0.0178%,P <0.01) significantly increased. The expression levels of NLRP3, ASC, and Caspase-1 were changed significantly (P< 0.05). In summary, the Chaihu-Shugan-San decoction modulated intestinal microbe dysbiosis, reduced fat accumulation, and alleviated inflammatory factor expression, which are all processes related to the NLRP3 inflammasome pathway in NAFLD rats.


Author(s):  
Abdel-Moniem A. Makhlouf ◽  
Atef M. Mahmoud ◽  
Rania G. Ibrahim ◽  
Yasmeen S. Abdel Aziz

Purpose: This study was aimed to evaluate the antioxidant and anti-inflammatory effects of vitamin D and Simvastatin (SIM) on a high-fat diet (HFD) induced-obese rats. Methods: 40 adult male rats were divided into four groups: control group, HFD, HFD + vitamin D, and HFD + SIM for 14 weeks. Vitamin D or SIM supplementation was done for the last 6 weeks. Vitamin D dosage was 500 IU/kg, while SIM dosage was 10 mg/kg. Interleukin-6 (IL-6) concentration and markers of oxidative stress including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione(GSH) concentrations in serum were determined using ELISA kits and spectrophotometry methods, respectively. Results: Treatment with vitamin D or SIM could significantly reduce IL-6 and MDA and increases SOD, GPx activities, and GSH levels. Oxidative stress can result not only from increased ROS production but also from dysfunctional antioxidant defenses. Conclusion: From the experimental results, it was observed that SIM and vitamin D could attenuate oxidative stress and inflammation markers associated with obesity.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260546
Author(s):  
Mary J. Obayemi ◽  
Christopher O. Akintayo ◽  
Adesola A. Oniyide ◽  
Ayodeji Aturamu ◽  
Olabimpe C. Badejogbin ◽  
...  

Background Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. Materials and methods Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. Results HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. Conclusion Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.


Author(s):  
ZAFAR JAVED KHAN ◽  
NAEEM AHMAD KHAN

Objective: The aim of the present study was to investigate the in vivo antioxidant potential of 50% ethanolic extract of Sesamum indicum against high-fat diet-induced rats. Methods: Animals were treated with plant extract for 30 d, and a high-fat diet was given to all groups except plain control, throughout, out the study. And alpha-tocopherol acetate (Vit, E) was used as standard. Pre-treatment with 16 mg/100 gm of body weight of 50% ethanolic extract of Sesamum indicum improved the Superoxide dismutase, catalase, glutathione, and lipid peroxidation levels significantly as compared to control group. Results: The present studies revealed that Sesamum indicum has significant in vivo antioxidant activity and can be used to protect tissue from oxidative stress. The result showed that the activities of SOD, catalase, lipid peroxidase, and glutathione, in the group treated with high-fat diet declined significantly than that of normal group. Conclusion: 50% ethanolic extract of in the dose of Sesamum indicum 16 mg/100 gm of body weight, has improved the SOD, catalase, glutathione, and lipid peroxidase levels significantly, which were comparable with high-fat-diet-induced rats. Based on this study we conclude that the 50% ethanolic extract of Sesamum indicum possesses in vivo antioxidant activity and can be employed in protecting tissue from oxidative stress.


2018 ◽  
Vol 88 (5-6) ◽  
pp. 234-243
Author(s):  
Soo Im Chung ◽  
Catherine W. Rico ◽  
Sang Chul Lee ◽  
Mi Young Kang

Abstract. The effects of instant cooked rice made from a combination of white rice and pigmented giant embryonic Keunnunjami rice, in comparison with those of instant regular white or brown rice and instant non-pigmented giant embryonic brown rice, on the glucose metabolism and antioxidant defense status in high-fat diet-fed mice were investigated. 56 male C57BL/6N mice were randomly divided into 7 dietary groups: normal control, high fat (23 %, HF), and HF supplemented with normal white (HF + NW) or brown rice (HF + NB), non-pigmented giant embryonic rice (HF + GB), and white rice with 8 % Keunnunjami (HF + KJ8) and 18 % Keunnunjami (HF + KJ18). After 7 weeks, HF mice showed marked increases in blood glucose (156 mg/dL), plasma insulin (12.1 mg/mL), and lipid peroxidation, and a significant decrease in hepatic glycogen (14.2 mg/g) relative to the control group (p < 0.05). However, addition of instant NB, GB, KJ8, andKJ18) rice suppressed this high-fat diet-induced hyperglycemia and oxidative stress through altering glucose-regulating enzymes (glucokinase, glucose-6-phosphatase, and phosphoenolpyruvate carboxykinase) and activation of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, glutathione reductase, and paraoxonase). Compared with HF mice, HF + KJ8 and HF + KJ18 groups exhibited significantly lower glucose (139–141 mg/dL), insulin (10.6–10.9 mg/mL), and lipid peroxidation and higher glycogen (15.3–16.4 mg/g) (p < 0.05). The hypoglycemic and antioxidant effects of instant KJ8 and KJ18 rice were generally comparable to those of instant NB and GB rice. These findings illustrate that instant rice made from white rice with 8 % Keunnunjami rice may be useful as a functional food with therapeutic potential against hyperglycemia and oxidative damage.


2008 ◽  
Vol 197 (2) ◽  
pp. 287-296 ◽  
Author(s):  
R Vinayagamoorthi ◽  
Zachariah Bobby ◽  
M G Sridhar

The oxidative stress-sensitive c-Jun-N-terminal kinase (JNK) pathway is known to be activated in diabetic condition and is involved in the progression of insulin resistance. However, the effect of antioxidants on JNK pathway and insulin resistance has not been investigated. The present study was aimed to investigate the effect of antioxidants on redox balance, insulin sensitivity, and JNK pathway in high-fat-fed rats. Male Wistar rats were divided into four groups: the control group – received a rodent chow; control+antioxidant group – fed with rodent chow supplemented with 0.2% (w/w) vitamin E, 0.3% (w/w) vitamin C, and 0.5% (w/w) α-lipoic acid; high-fat group – received high-fat diet; and high fat+antioxidant group – fed with high-fat diet supplemented with above antioxidants. Fat feeding to rats for 9 weeks significantly increased IRS-1 serine phoshorylation, reduced insulin-stimulated IRS-1 tyrosine phosphorylation and insulin sensitivity. High-fat diet also impaired redox balance and activated the redox-sensitive serine kinase – JNK pathway. Antioxidant supplementation along with high-fat diet preserved the free radical defense system, inhibited the activation of JNK pathway, and improved insulin signaling and insulin sensitivity. The present study shows for the first time that antioxidants inhibit JNK pathway and IRS-1 serine phosphorylation while improving insulin sensitivity in fat-fed rats. These findings implicate the beneficial effect of antioxidants in obesity-/dyslipidemia-induced insulin resistance in humans.


2019 ◽  
Vol 44 (7) ◽  
pp. 774-782 ◽  
Author(s):  
Sevda Tanrıkulu-Küçük ◽  
Canan Başaran-Küçükgergin ◽  
Muhammed Seyithanoğlu ◽  
Semra Doğru-Abbasoğlu ◽  
Hikmet Koçak ◽  
...  

This study investigated the effects of curcumin and capsaicin on testicular and hepatic oxidant–antioxidant status in rats fed a high-fat diet (HFD). Male Sprague–Dawley rats were divided into 5 groups (8 rats per group). The control group was fed a normal control diet (standard laboratory chow), the HFD group was fed HFD (60% of total calories from fat), the HFD+CUR group received HFD supplemented with curcumin (1.5 g curcumin/kg HFD), the HFD+CAP group was given HFD supplemented with capsaicin (0.15 g capsaicin/kg HFD), and the HFD+CUR+CAP group received HFD supplemented with curcumin and capsaicin for 16 weeks. Hepatic and testicular thiobarbituric acid reactive substances (TBARS), reactive oxygen species (ROS), glutathione (GSH) levels, glutathione transferase activity, and Cu-Zn superoxide dismutase, glutathione peroxidase, and catalase protein expression and enzyme activities were measured. Protein expression was determined by Western blotting. GSH levels and antioxidant enzyme activities were measured with colorimetric methods. HFD slightly increased hepatic and testicular oxidative stress parameters. GSH levels did not change between groups. TBARS and ROS levels were significantly reduced in the HFD+CUR+CAP group compared with the HFD group. Liver and testis antioxidant enzyme activities and expression increased significantly with combined capsaicin and curcumin treatment. Curcumin and capsaicin treatment attenuated testicular and hepatic oxidative stress and enhanced the antioxidant defense system. The combination of capsaicin and curcumin with HFD seems to have some remarkable and beneficial effects on testicular oxidative damage in the fatty liver rat model.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 165
Author(s):  
Aziza Alrafiah

High-fat diet (HFD) is a major problem causing neuronal damage. Thymoquinone (TQ) could regulate oxidative stress and the inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation, as well as morphological changes in the cerebellum of rats with HFD. Rats were divided into three groups as (1) control, (2) saturated HFD for eight weeks and (3) HFD supplementation (four weeks) followed by TQ 300 mg/kg/day treated (four weeks). After treatment, blood samples were collected to measure oxidative stress markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher body weight (286.5 ± 7.4 g) as compared with the control group (224.67 ± 1.78 g). TQ treatment significantly (p < 0.05) lowered the body weight (225.83 ± 13.15 g). TQ produced a significant (p < 0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The antioxidative enzymes significantly reduced in HFD rats (GSH, 1.46 ± 0.36 mol/L and SOD, 99.13 ± 5.41 µmol/mL) as compared with the control group (GSH, 6.25 ± 0.36 mol/L and SOD, 159.67 ± 10.67 µmol/mL). MDA was increased significantly in HFD rats (2.05 ± 0.25 nmol/L) compared to the control group (0.695 ± 0.11 nmol/L). Surprisingly, treatment with TQ could improve the level of GSH, MDA, and SOD. TQ treatment significantly (p < 0.05) reduced the inflammatory markers as compared with HFD alone. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves antioxidant enzymes. TQ can be considered as a promising agent in preventing the neuronal morphological changes in the cerebellum of obese populations.


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