scholarly journals Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Reza Ashrafi ◽  
Marianne Yon ◽  
Lucy Pickavance ◽  
Joseph Yanni Gerges ◽  
Gershan Davis ◽  
...  

Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules.Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n=8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation ofCav1.2, HCN4,Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+transient, both of which would be expected to be arrhythmogenic.Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.

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.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Matthew R Peterson ◽  
Samantha Haller ◽  
Tracy Ta ◽  
Luiza Bosch ◽  
Aspen Smith ◽  
...  

NLR family, pyrin domain-containing 3 (NLRP3) is a pattern recognition receptor responsible for perpetuating an inflammatory response through production of pro-inflammatory cytokines IL-1β and IL-18. It has been implicated in the sustained inflammatory response in obesity and multiple cardiovascular disease conditions. In order to investigate NLRP3 as a potential therapeutic target in metabolic syndrome, C57BL/6 wild-type (WT) and NLRP3 knockout (NLRP3-\-) mice were fed a normal diet (ND; 12% fat chow) or a high fat diet (HFD; 45% fat chow) for 5 months. At 5 months, echocardiography and glucose tolerance tests (GTTs) were performed. Cardiac function assessed by fractional shortening (FS) was significantly impaired by HFD feeding in the WT group (0.335 HFD vs. 0.456 ND; p<0.05) but not in the NLRP3-\- (0.449 HFD vs. 0.492 ND; p>0.05). FS was higher in NLRP3-\-HFD than in WT-HFD (p<0.05). Two-dimensional analysis shows the FS difference between NLRP3-\-HFD and WT-HFD was primarily explained by the difference in left ventricular end-systolic dimension (0.2716 cm WT vs. 0.1883 cm NLRP3-\-; p<0.05). Glucose tolerance measured by area under the curve (AUC) was significantly impaired by HFD feeding for both WT (23183 ND vs. 57298 HFD; p<0.001) and NLRP3-\- (23197 ND vs. 44626 HFD; p<0.001), but significantly better in the NLRP3-\-HFD than in WT-HFD (p<0.01). HFD feeding increased fasting blood glucose (FBG) for both WT (97.7 mg . dl -1 ND vs. 164.7 mg . dl -1 HFD; p<0.01) and NLRP3-\- (80.50 mg . dl -1 ND vs. 108.8 mg . dl -1 HFD; p<0.05), but significantly less in NLRP3-\- mice (NLRP3-\- vs. WT; p<0.05). For GTTs, body weight was significantly higher in the WT than NLRP3-\- fed HFD (47.93 g vs. 36.5 g; p<0.001). Body weight explained 92% of variation in glucose tolerance (p<0.0001) and 69% of variation in fasting blood glucose (p<0.0001). WT-HFD averaged 1.31X heavier than NLRP3-\-HFD, while the AUC for the IGTT was 1.28X larger for the WT-HFD than NLRP3-\-HFD. Body weights were not significantly different between genotypes at the time of echo. The results suggest that knockout of NLRP3 may be protective against HFD induced cardiovascular dysfunction. A protective effect on glucose tolerance is not strongly supported.


2006 ◽  
Vol 55 (6) ◽  
pp. 305-314 ◽  
Author(s):  
Yutaka OHTA ◽  
Manabu SAMI ◽  
Tomomasa KANDA ◽  
Kenji SAITO ◽  
Kyoichi OSADA ◽  
...  

Nutrients ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1215 ◽  
Author(s):  
Laura Elvira-Torales ◽  
Inmaculada Navarro-González ◽  
Rocío González-Barrio ◽  
Gala Martín-Pozuelo ◽  
Guillermo Doménech ◽  
...  

The objective of this work was to identify the effect of tomato juice on the expression of genes and levels of metabolites related to steatosis in rats. Male Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice). After an intervention period of 5 weeks, rats were sacrificed and biochemical parameters, biomarkers of oxidative stress, liver metabolites, and gene expression were determined. Although the H diet provoked dislipemia related to steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were observed. Changes in the gene expression of the HA group were produced by the high consumption of fat, whereas the consumption of tomato juice had different effects, depending on the diet. In the NL group, the genes involved in β-oxidation were upregulated, and in groups NL and HL upregulation of CD36 and downregulation of APOB and LPL were observed. In addition, in the HL group the accumulation of lycopene upregulated the genes FXR and HNF4A, which have been suggested as preventive factors in relation to steatosis. Regarding the metabolomics study, intake of tomato juice stimulated the biosynthesis of glutathione and amino acids of the transulfurization pathway, increasing the levels of metabolites related to the antioxidant response.


Zygote ◽  
2016 ◽  
Vol 24 (5) ◽  
pp. 676-683 ◽  
Author(s):  
Driele Neske Garcia ◽  
Lígia Antunes Prietsch ◽  
Joao Alveiro Alvarado Rincón ◽  
Iraê de Lima Moreira ◽  
Sandra Costa Valle ◽  
...  

SummaryThe aim of this study was to compare serum lipid profiles and ovarian gene expression between aged and younger female mice fed a control or a high-fat diet for 2 months. For this 16 female mice (C57BL/6) of 4 months (Young, n = 8) or 13 months (Old, n = 8) of age were used. The females were divided into four groups: (i) young females fed a normal diet; (ii) young females fed a high-fat diet; (iii) old females fed a normal diet; and (iv) old females fed a high-fat diet. Food intake was reduced (P < 0.05) in mice fed with a high-fat (2.9 ± 0.1 g) diet in comparison with control mice (3.9 ± 0.1 g). Body weight was higher for old females on the high-fat diet (35.1 ± 0.3 g) than for young females on the same diet (23.3 ± 0.4 g; P < 0.05). PON1 activity was lower in the high-fat than control diet group (114.3 ± 5.8 vs. 78.1 ± 6.0 kU/L, respectively) and was higher in older than younger females (85.9 ± 6.4 vs. 106.5 ± 5.3; P < 0.05, respectively). Females fed a high-fat diet had lower expression of Igf1 mRNA (P = 0.04). There was an interaction between age and diet for the expression of Gdf9 and Survivin, with lower expression in older females in both diets and young females that received the high-fat diet (P < 0.05). Concluding, the high-fat diet reduced the expression of ovarian Igf1 mRNA, and Gdf9 and Survivin mRNA in younger females, which can indicate lower fertility rates. High-density lipoprotein concentration and PON1 activity were higher in aged female mice.


2020 ◽  
Vol 10 (2) ◽  
pp. 106-117
Author(s):  
Maryam Mostafavian ◽  
◽  
Ahmad Abdi ◽  
Javad Mehrabani ◽  
Alireza Barari ◽  
...  

Objective: Decreased physical activity coupled with increased High‐Fat Diet (HFD) intake prompts obesity. Current research suggests that changing White Adipose Tissue (WAT) to brown promotes energy expenditure to counter obesity. The purpose of this study was to investigate the effects of aerobic Progressive training and Capsaicin (Cap) on Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and Uncoupling protein-1 (UPC-1) gene expression in rat fed a high-fat diet. Methods: 40 male Wistar rats aged 8-12 weeks, were fed a Normal Diet (ND) (n=8) or HFD (n=32) for 8 weeks. After 8 weeks, rats were divided into 5 groups: ND, HFD, High-Fat Diet-Training (HFDT), High-Fat Diet-Capsaicin (HFDCap), high-fat diet-training-capsaicin (HFDTCap). Training groups have performed a progressive aerobic running program on a motor-driven treadmill for eight weeks. Capsaicin (4 mg/kg/day) were administered orally, by gavage, once a day. PGC-1α and UCP-1 gene expression levels in the VAT were measured by Real-time PCR method. Results: The results of this study showed that PGC-1α and UCP-expression was decreased in HFD group compared to ND group. Also, the expression of PGC-1α and UPC-1 in HFDT, HFDCap and HFDTCap groups was significantly increased compared to HFD. The expression of PGC-1α and UPC-1 in HFDTCap was also significantly increased compared to HFDT and HFDCap groups. Conclusion: Possibly, eight weeks of progressive training combined with capsaicin administration has an effect on the browning of visceral adipose tissue in HFD rats by increasing expression of PGC-1α and UCP-1.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Wanpitak Pongkan ◽  
KEWARIN JINAWONG ◽  
Siriporn Chattipakorn ◽  
Nipon CHATTIPAKORN

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.


Author(s):  
Katsuyuki Tokinoya ◽  
Seiko Ono ◽  
Kai Aoki ◽  
Koki Yanazawa ◽  
Yasuhiro Shishikura ◽  
...  

AbstractIntroductionExercise training is beneficial for reducing obesity. In particular, exercise training can lower the catecholamine concentration in circulation. Renalase, whose expression was first confirmed in the kidneys, is a physiologically active substance that decomposes circulating catecholamines; additionally, it has been reported to be present in the skeletal muscles. The aim of this study was to clarify the expression of renalase in the skeletal muscles and kidneys after high-intensity exercise training in obese mice.Material and methodsThe mice were divided into four groups: normal diet and sedentary, normal diet and exercise training, high-fat diet and sedentary, and high-fat diet and exercise training, and the test was performed for 8 weeks.ResultsBody weight and skeletal muscle wet weight were reduced by high-fat diet intake but were rescued by training. Skeletal muscle renalase gene expression was significantly increased by exercise training. However, in the kidneys the gene expression of renalase was significantly increased by high-fat diet intake and exercise training. No significant changes were observed in the gene expression of catecholamine-degrading enzymes, catechol-O-methyltransferase and monoamine oxidase A and B.ConclusionWe demonstrated that exercise training increased the gene expression of renalase in the skeletal muscles and kidneys, thus lowering circulating catecholamine levels. This may lead to amelioration of obesity as catecholamines are lipolytic.


Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3565-3576 ◽  
Author(s):  
Michael Kruse ◽  
Yoshinori Seki ◽  
Patricia M. Vuguin ◽  
Xiu Quan Du ◽  
Ariana Fiallo ◽  
...  

Altered fetal environments, such as a high-fat milieu, induce metabolic abnormalities in offspring. Different postnatal environments reveal the predisposition for adult diseases that occur during the fetal period. This study investigates the ability of a maternal high-fat diet (HFD) to program metabolic responses to HFD reexposure in offspring after consuming normal chow for 23 weeks after weaning. Wild-type CD1 females were fed a HFD (H) or control (C) chow during pregnancy and lactation. At 26 weeks of age, offspring were either reexposed (H-C-H) or newly exposed (C-C-H) to the HFD for 19 weeks. Body weight was measured weekly, and glucose and insulin tolerance were measured after 10 and 18 weeks on the HFD. The metabolic profile of offspring on a HFD or C diet during pregnancy and lactation and weaned onto a low-fat diet was similar at 26 weeks. H-C-H offspring gained more weight and developed larger adipocytes after being reintroduced to the HFD later in life than C-C-H. H-C-H mice were glucose and insulin intolerant and showed reduced gene expression of cox6a2 and atp5i in muscle, indicating mitochondrial dysfunction. In adipocytes, the expression of slc2a4, srebf1, and adipoq genes was decreased in H-C-H mice compared with C-C-C, indicating insulin resistance. H-C-H showed extensive hepatosteatosis, accompanied by increased gene expression for cd36 and serpin1, compared with C-C-H. Perinatal exposure to a HFD programs a more deleterious response to a HFD challenge later in life even after an interval of normal diet in mice.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Krekwit Shinlapawittayatorn ◽  
Wanpitak Pongkan ◽  
Sivaporn Sivasinprasasn ◽  
Siriporn Chattipakorn ◽  
Nipon CHATTIPAKORN

Introduction: Male gender and menopause increase the risk for cardiovascular incidence. However, less is known about gender differences in cardiometabolic disorders, particularly under obese-insulin resistant and sex hormone-deprived conditions. Hypothesis: Male have worse cardiometabolic disorders than female under obese-insulin resistant and sex hormone-deprived conditions. Methods: Adult Wistar rats of both sexes (n=20) were randomly assigned into four groups (n = 5/group): male normal diet sham (M-NDS), male high fat-diet with orchiectomy (M-HFO), female normal diet sham (F-NDS) and female high fat-diet with ovariectomy (F-HFO). Rats were fed either a normal diet (19.77% of energy fat) or a high-fat diet (57.60% of energy fat) for 12 weeks following the induction of sex hormone deprivation by either bilateral orchiectomy or ovariectomy. Temporal determinations of metabolic parameters, heart rate variability (HRV), left ventricular (LV) function, and cardiac mitochondrial function at 4, 8, and 12 weeks were done after starting each feeding program. Results: Insulin resistance was initially observed after 8 weeks of high-fat diet consumption in both M-HFO and F-HFO groups. In addition, M-HFO had depressed HRV, impaired LV performance indicated by decreased ejection fraction (%EF) and cardiac mitochondrial dysfunction indicated by increased mitochondrial ROS level, depolarization and swelling, as early as week 4, whereas F-HFO exhibited them at week 8 or 12. Moreover, at week 12, M-HFO have worse cardiometabolic disorders than F-HFO, particularly %EF and HRV. Conclusions: Under sex hormone-deprived condition, male are generally more susceptible to cardiometabolic disorders and cardiac mitochondrial dysfunction, especially in the presence of obese-insulin resistant condition.


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