scholarly journals Dietary supplementation with fish oil alters the expression levels of proteins governing mitochondrial dynamics and prevents high-fat diet-induced endothelial dysfunction

2014 ◽  
Vol 112 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Ruifang Sun ◽  
Xiaoming Wang ◽  
Yan Liu ◽  
Min Xia

Diets supplemented with fish oil (FO), which is rich in n-3 PUFA, have been shown to modify several key risk factors for CVD. The purpose of the present study was to determine the effect of FO supplementation on mitochondrial dynamic protein expression in the endothelium and on endothelial cell function. Male apoE-deficient (apoE− / −) mice (8 weeks old, n 12 per group) were fed a high-fat diet containing 45 % fat (HFD group) or a HFD with partial replacement of lard with 10 % (w/w) FO (FO group) (total EPA and DHA content 64·1 g/kg) for 8 weeks. ApoE− / − mice in the FO group had a greater endothelium-dependent vasorelaxation response to acetylcholine (Ach) than those in the HFD group. The atherosclerotic lesion volume in the aortic sinus of mice in the FO group was 54 % lower than that in the HFD group (P< 0·01). In addition, the aortas isolated from mice in the FO group had higher expression levels of Mfn2 and Opa1 but lower expression levels of Fis1 than those from the HFD group. Compared with mice fed the HFD, those fed the FO diet showed significantly lower levels of mitochondrial oxidative stress, cytochrome c release and caspase-3 activity (each P< 0·05). Furthermore, FO-fed mice displayed increased NO release and availability and enhanced endothelial NO synthase activity compared with HFD-fed mice. Taken together, these results reveal a novel mechanism by which FO protects against endothelial cell dysfunction, which may result in improved mitochondrial dynamics.

2016 ◽  
Vol 60 (11) ◽  
pp. 2493-2504 ◽  
Author(s):  
Lorraine S. Oliveira ◽  
Luana L. Souza ◽  
Aline F. P. Souza ◽  
Aline Cordeiro ◽  
George E. G. Kluck ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rieko Takanabe ◽  
Koh Ono ◽  
Tomohide Takaya ◽  
Takahiro Horie ◽  
Hiromichi Wada ◽  
...  

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.


2013 ◽  
Vol 91 (11) ◽  
pp. 960-965 ◽  
Author(s):  
Kelby Cleverley ◽  
Xiaozhou Du ◽  
Sheena Premecz ◽  
Khuong Le ◽  
Matthew Zeglinski ◽  
...  

Owing to their spontaneous development of atherosclerosis, apolipoprotein E knockout mice (ApoEKO) are one of the best studied animal models for this disease. Little is known about the utility of various omega-3 fatty acid regimens, in particular fish oils, in preventing cardiac disease in ApoEKO mice. The purpose of this study was to determine the cardiovascular effects of omega-3 fatty acid supplementation with either safflower oil (control), fish oil, flaxseed oil, or designed oil in ApoEKO mice fed a high-fat diet for a total of 16 weeks. In-vivo cardiac function was assessed weekly using murine echocardiography. Blood pressure, plasma lipid levels, and brain natriuretic peptide (BNP) were serially measured. The results show that ApoEKO mice fed fish oil demonstrated an increase in left ventricular wall thickness as a result of increased afterload. Despite chronic treatment with fish oil over 16 weeks, blood pressure increased in ApoEKO mice by 20% compared with the baseline. Both echocardiographic evidence of left ventricular hypertrophy and biochemical increase in BNP levels confirmed diastolic dysfunction in ApoEKO mice fed fish oil. This suggests that high-fat diet supplemented with fish oil may lead to adverse cardiovascular effects in ApoE deficient mice.


Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5428-5437 ◽  
Author(s):  
Johan Bourghardt ◽  
Anna S. K. Wilhelmson ◽  
Camilla Alexanderson ◽  
Karel De Gendt ◽  
Guido Verhoeven ◽  
...  

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P &lt; 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P &lt; 0.001) and ARKO mice (by 24%, P &lt; 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P &lt; 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P &lt; 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.


2016 ◽  
Vol 6 (3) ◽  
pp. 144 ◽  
Author(s):  
Takuya Yamane ◽  
Miyuki Kozuka ◽  
Yoshio Yamamoto ◽  
Yoshihisa Nakano ◽  
Takenori Nakagaki ◽  
...  

Background: Aronia berries have many potential effects on health, including an antioxidant effect, effect for antimutagenesis, hepatoprotection and cardioprotection, an antidiabetic effect and inhibition of cancer cell proliferation. Previous human studies have shown that aronia juice may be useful for treatment of obesity disorders.Objective: To reveal relationship between beneficial effect and the gene expression change by aronia berries, we analyzed mice livers using RNA sequencing and RT-qPCR.Method: At 28 days after starting a normal diet, a high fat diet and a high-fat diet containing 10% freeze-dried aronia berries, serum was obtained from veins of mice after isoflurane anesthesia, and liver tissues were isolated and weighed. Triglyceride, total cholesterol and LDL cholesterol levels were measured and total RNAs were extracted. cDNA libraries were prepared according to Illumina protocols and sequenced using an Illumina HiSeq2500 to perform 100 paired-end sequencing. RNA-sequence reads mapping was performed using a DNA nexus. Gene expression analysis was performed. The liver tissue specimens were fixed and embedded in paraffin. After 5-mm-thick paraffin sections had been cut, they were stained with hematoxylin-eosin using the standard procedure and also with Sirius Red.Results: In this study, we found that mild fibrosis induced by a high-fat diet was reduced in livers of mice fed a high-fat diet containing aronia berries. RNA sequencing and RT-qPCR analyses revealed that gene expression levels of Igfbp1 and Gadd45g were increased in livers from mice fed a high-fat diet containing aronia berries. Furthermore, results of an enzyme-linked immunoassay showed that a secreted protein levels of FABP1 and FABP4 were reduced in serum from mice fed a high-fat diet containing aronia berries. The results suggest that aronia berries have beneficial effects on mild fibrosis in liver.Conclusion: Aronia berries have a beneficial effect on liver fibrosis. The recovery from liver fibrosis is associated with expression levels of Gadd45g and Igfbp1 in the liver. The beneficial effects of aronia berries on liver fibrosis reduce the risk of liver cancer diseases and insulin resistance, resulting in reduction of serum FABP1 and FABP4 levels.Keywords: aronia; fibrosis; liver; Igfbp1; Gadd45g


PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0186216 ◽  
Author(s):  
Chenxi Cui ◽  
Yanyan Li ◽  
Hang Gao ◽  
Hongyan Zhang ◽  
Jiaojiao Han ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Yanliu Lu ◽  
Yimei Du ◽  
Lin Qin ◽  
Di Wu ◽  
Wei Wang ◽  
...  

Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL-C levels. The gene expression level of Shp was downregulated while the levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine-conjugated bile acids while decreasing glycine-conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.


2019 ◽  
Vol 150 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Jay J Cao ◽  
Brian R Gregoire ◽  
Kim G Michelsen ◽  
Matthew J Picklo

ABSTRACT Background Intake of total fat is linked to obesity and inversely associated with bone density in humans. Epidemiologic and animal studies show that long-chain n–3 (ω-3) PUFAs supplied as fish oil (FO) are beneficial to skeletal health. Objective This study tested the hypothesis that increasing dietary FO would decrease adiposity and improve bone-related outcomes in growing obese mice. Methods Male C57BL/6 mice at 6 wk old were assigned to 6 treatment groups and fed either a normal-fat diet (3.85 kcal/g and 10% energy as fat) or a high-fat diet (HF; 4.73 kcal/g and 45% energy as fat) containing either 0%, 3%, or 9% energy as FO (0FO, 3FO, and 9FO, respectively) ad libitum for 6 mo. Bone structure, body composition, and serum bone-related cytokines were measured. Results The HF diet increased the expression of the adipose tissue tumor necrosis factor α (Tnfa) and serum concentrations of leptin and tartrate-resistant acid phosphatase (TRAP), and decreased serum concentrations of osteocalcin and bone-specific alkaline phosphatase (P &lt; 0.05). FO decreased fat mass (P &lt; 0.05), serum TRAP (P &lt; 0.05), and adipose tissue Tnfa expression (P &lt; 0.01). Bone content of long-chain n–3 PUFAs was increased and n–6 PUFAs were decreased with the elevation in dietary FO content (P &lt; 0.01). Compared with mice fed 9FO, animals fed 3FO had higher femoral bone volume/total volume (25%), trabecular number (23%), connectivity density (82%), and bone mass of second lumbar vertebrae (12%) and lower femoral trabecular separation (−19%). Mice fed the 3FO HF diet had 42% higher bone mass than those fed the 0FO HF diet. Conclusions These data indicate increasing dietary FO ≤3% energy can decrease adiposity and mitigate HF diet–induced bone deterioration in growing C57BL/6 mice possibly by reducing inflammation and bone resorption. FO at 9% diet energy had no further beneficial effects on bone of obese mice.


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