scholarly journals The Role of Exercise in Reducing Hyperlipidemia-Induced Neuronal Damage in Apolipoprotein E-Deficient Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yumeng Bai ◽  
Yali Feng ◽  
Bo Jiang ◽  
Yan Yang ◽  
Zuowei Pei ◽  
...  

Hyperlipidemia causes nervous system-related diseases. Exercise training has developed into an established evidence-based treatment strategy that is beneficial for neuronal injury. This study investigated the effect of exercise on hyperlipidemia-induced neuronal injury in apolipoprotein E-deficient (ApoE-/-) mice. Male ApoE-/- mice (age: 8 weeks) were randomly divided into four groups as follows: mice fed a normal diet (ND), normal diet+swimming training (ND+S), high-fat diet (HD), and high-fat diet+swimming (HD+S). Exercise training consisted of swimming for 40 min/day, 5 days/week for 12 weeks. After 12 weeks, we measured serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c). We also evaluated glial fibrillary acidic protein (GFAP) expression levels using immunohistochemistry, real-time PCR, and immunoblotting. In addition, NLR family pyrin domain-containing 3 (NLRP3), interleukin- (IL-) 18, caspase-1, Bax, Bcl-2, and phosphorylated extracellular signal-regulated kinase (p-ERK) expression levels were measured using immunoblotting. Serum levels of TG, TC, and LDL-c were lower in ApoE-/- HD+S mice than in ApoE-/- HD mice. Immunohistochemistry, real-time PCR, and immunoblotting showed increased levels of GFAP in the ApoE-/- HD group. Immunoblotting revealed increased levels of NLRP3, IL-18, caspase-1, Bax, Bcl-2, and p-ERK in the ApoE-/- HD group; however, they were significantly suppressed in the ApoE-/- HD+S group. Therefore, exercise has protective effects against neuronal injury caused by hyperlipidemia.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoyuan Sui ◽  
Lianqun Jia ◽  
Nan Song ◽  
Dongyu Min ◽  
Si Chen ◽  
...  

Abstract Background A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. Methods Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs. Results Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis. Conclusions Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required.


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.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Sharvari S. Deshpande ◽  
Harishankar Nemani ◽  
Gandhimathi Arumugam ◽  
Avinash Ravichandran ◽  
Nafisa H. Balasinor

Abstract Background Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation. Results We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group. Conclusion Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fang Li ◽  
Qian Li ◽  
Yu Zhang ◽  
Xianrong Zhou ◽  
Ruokun Yi ◽  
...  

Xylooligosaccharide (XOS) is a source of prebiotics with multiple biological activities. The present study aimed to investigate the effects of XOS on mice fed a high-fat diet. Mice were fed either a normal diet or a high-fat diet supplemented without or with XOS (250 and 500 mg/kg), respectively, for 12 weeks. The results showed that the XOS inhibited mouse weight gain, decreased the epididymal adipose index, and improved the blood lipid levels, including triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels. Moreover, XOS reduced the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and alleviated the damage to the liver caused by the high-fat diet. XOS also reduced hyperlipidemia-associated inflammatory responses. Additionally, quantitative real-time polymerase chain reaction results showed that XOS intervention activated the AMP-activated protein kinase (AMPK) pathway to regulate the fat synthesis, decomposition, and β oxidation; upregulated the mRNA expression levels of carnitine palmitoyl transferase 1 (CPT-1), peroxisome proliferator–activated receptors α (PPAR-α), and cholesterol 7-alpha hydroxylase (CYP7A1); and downregulated the mRNA expression levels of acetyl-CoA carboxylase (ACC), CCAAT/enhancer-binding protein alpha (C/EBPα), and lipoprotein lipase (LPL). On the other hand, XOS enhanced the mRNA expression levels of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the small intestine; increased the strength of the intestinal barrier; and optimized the composition of the intestinal microbiota. Therefore, it was concluded that XOS regulated the intestinal barrier, changed the intestinal microecology, and played an important role in preventing hyperlipidemia through the unique anatomical advantages of the gut–liver axis.


2018 ◽  
Vol 47 (5) ◽  
pp. 1862-1870 ◽  
Author(s):  
Tian Yang ◽  
Xiaobo Wu ◽  
Jimeng Hu ◽  
Mengbo Hu ◽  
Hua Xu ◽  
...  

Background/Aims: We aim to investigate the impact of maternal high fat diet (HFD) on the development and progression of prostate cancer (PCa) in transgenic adenocarcinoma mouse prostate (TRAMP) offspring. Methods: The TRAMP model was used, and divided into maternal HFD group and normal diet (ND) group in the present study. Each group contained 36 TRAMP mice. Serum levels of leptin, adiponectin, interleukin (IL) -1α, IL-1β, IL-6, tumor necrosis factor-α and monocyte chemotactic protein-1 were measured by the 20th, 24th and 28th week old through ProcartaPlex Multiplex Immunoassay. Body fat ratio was measured by MiniQMR. Tumor formation rate was measured through hematoxylin and eosin (H&E) staining, and mortality rate was measured meantime. Western blot was applied to determine the levels of Protein Kinase B (Akt) and Phosphatase and tensin homolog (PTEN). Results: The mortality rate of maternal HFD group was significantly higher than that of ND group (P = 0.046). The tumor formation rate was significantly higher in maternal HFD group than in ND group only in 20th week subgroup (P = 0.040). A significant increase of leptin was seen in maternal HFD 20th and 24th week subgroups (P = 0.001 and < 0.001, respectively) and a decrease of adiponectin was seen in maternal HFD 20th and 28th week subgroups (P =0.006 and < 0.001, respectively). Besides, an activated phos-Akt (P-Akt) and deactivated PTEN were observed in maternal HFD group. Conclusions: Maternal HFD could increase the standard serum leptin level, inhibit the expression of PTEN protein, promote P-Akt protein expression, activate the PI3K/Akt pathway, and ultimately promote the development and progression of PCa in TRAMP offspring.


2008 ◽  
Vol 33 (3) ◽  
pp. 461-469 ◽  
Author(s):  
Ryan Jankord ◽  
Venkataseshu K. Ganjam ◽  
James R. Turk ◽  
Marc T. Hamilton ◽  
M. Harold Laughlin

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo–pituitary–adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16–20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted ACTH response to an acute stressor in sedentary animals, but cannot explain the exaggerated response in exercise trained animals.


2007 ◽  
Vol 293 (3) ◽  
pp. H1553-H1563 ◽  
Author(s):  
Yan Yang ◽  
Allan W. Jones ◽  
Tom R. Thomas ◽  
Leona J. Rubin

Potassium channels in vascular smooth muscle (VSM) control vasodilation and are potential regulatory targets. This study evaluated effects of sex differences, exercise training (EX), and high-fat diet (HF) on K+ currents ( IK) of coronary VSM cells. Yucatan male and female swine were assigned to either sedentary confinement (SED), 16 wk of EX, 20 wk of HF, or 20 wk of HF with 16 wk of EX (HF-EX). VSM cells of normal-diet SED animals exhibited three components of IK: 4-aminopyridine-sensitive IK(KV), TEA-sensitive IK(BK), and 4-aminopyridine + TEA-insensitive IK. Females exhibited significantly higher basal IK than males in the same group. EX increased basal IK in males and females. HF reduced IK in males and females and nullified effects of EX. Endothelin-1 increased IK significantly in males but not in females. In the presence of endothelin-1, 1) IK(KV) was similar in SED males and females and EX increased IK(KV) to a greater extent in males than in females and 2) IK(BK) was greater in SED females than in males and EX increased IK(BK) to a greater extent in males, resulting in IK(BK) similar to EX females. Importantly, HF nullified effects of EX on IK(KV) and IK(BK). These data indicate that basal IK of SED female swine is inherently greater than that shown in SED males and that males require EX to achieve comparable levels of IK. Importantly, HF reduced IK in males and females and nullified effects of EX, suggesting HF abrogates beneficial effects of EX on coronary smooth muscle.


Vascular ◽  
2017 ◽  
Vol 26 (1) ◽  
pp. 18-26 ◽  
Author(s):  
Zhaojun Wang ◽  
Zhongqun Wang ◽  
Jie Zhu ◽  
Xinguang Long ◽  
Jinchuan Yan

Background and objectives Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified. Methods and results Eighteen ApoE-/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg−1.day−1) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE-/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4 mRNA at aortic tissues ( r = 0.77 and r = 0.79, respectively, both P < 0.001). Conclusion VitK2 can inhibit intimal calcification of aortic artery induced by high-fat diet in ApoE-/- mice and A7r5 SMCs calcification induced by β-sodium glycerophosphate, and meanwhile can reduce the expression of TLR2 and TLR4. These results suggested that the effects of VitK2 on vascular calcification may be associated with the expression of TLR2 and TLR4.


2020 ◽  
Vol 90 (3-4) ◽  
pp. 221-227 ◽  
Author(s):  
Onur Atakisi ◽  
Kezban Yildiz Dalginli ◽  
Canan Gulmez ◽  
Ruya Kaya ◽  
Ozkan Ozden ◽  
...  

Abstract. The aim of this study was to investigate the effects of boric acid (BA) and borax (BX) on live weight and obesity associated molecules including leptin, L-carnitine, insulin-like growth factor 1 (IGF-I), and heat shock proteins 70 (HSP70) in rats fed with high-fat diet. A total of 60 rats were equally allocated as ND (normal diet), HF (high-fat diet), HF+BA, HF+BX, ND+BX, ND+BA. Body weight increases in HF+BA (85 g) and HF+BX (86 g) were significantly lower (p<0.05) compared to HF group (126 g). Boron treatment decreased serum L-carnitine level in high-fat diet (HF+BA 11.12 mg/L, HF+BX 10.51 mg/L, p<0.05) compared to HF group (15.57 mg/L), while no change was observed in groups ND+BA (7.55 mg/L) and ND+BX (7.57 mg/L) compared to group ND (8.29 mg/L). Neither BA nor BX supplementation in ND and HF groups altered the serum levels of HSP70 and leptin. BA and BX supplementation in rats fed HF resulted in a significant reduction in live weight. Boron compounds altered L-carnitine and IGF-1 levels in rats. These results indicate that boron compounds are beneficial in the treatment of obesity as well as in the prevention of high-fat diet-induced weight increase. Alterations in serum L-carnitine and IGF-1 levels in boron treated rats also indicate possible role of boron compounds in energy metabolism in response to high fat diet.


2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Wen Jing ◽  
Chuanfen Li ◽  
Jingguo Zhao

 Objective Aerobic exercise can improve liver metabolic diseases such as non-alcoholic fatty liverdisease (NAFLD), but the molecular mechanism is not completely clear, which limits the applicationof aerobic exercise in the treatment and improvement of NAFLD. In this paper, the effects of aerobicexercise on the expression levels of important genes regulating fatty acid metabolism in the liver ofNAFLD rats were studied in order to explore the possible molecular mechanism of aerobic exerciseregulating hepatic fatty acid metabolism.Methods 1. Animal grouping. 36 male Sprague Dawley (SD) rats aged 21 days old were randomlydivided into three groups after 1 week of adaptive feeding: 10 in the normal diet quiet group (NCgroup), 10 in the high-fat diet quiet group (HC group) and 16 in the high-fat diet exercise group (HTgroup). 2. Training arrangements. After 12 weeks, the rats in the HT group underwent 8 weeks ofaerobic exercise with a training intensity of 25m/min, and continued exercise for 1h/d, 6d/w for atotal of 8 weeks. 3. Sample collection. After an overnight fast, rats in the three groups were weighedand anesthetized with an intraperitoneal injection of 10% chloral hydrate (0.3 ml/100 g bodyweight). Blood samples were collected from the aortaventralis, centrifuged, and kept frozen at -80 °Cfor chemical assays. The rat liver was removed, frozen in liquid nitrogen, and stored in a -80 °Cfreezer. 4. Serum lipid concentration and liver function detection. Serum levels of total cholesterol(TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoproteincholesterol (LDL-C), free fatty acid (FFA), aspartate aminotransferase (AST) and alanineaminotransferase (ALT) were detected in three groups of rats. 5. Detection of expression levels offatty acid metabolism related genes in liver. The expression levels of AMP-activated protein kinase(AMPK), silence information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α) in rat liver were detected by SYBR Green real-time PCR. 6. Data statistics.Results were expressed in the form of mean±standard deviation. Spss17.0 statistical software wasused to conduct one-way ANOVA to compare the differences between the groups, p<0.05 indicatessignificant difference between groups.Results 1. Effects of aerobic exercise on Blood lipids and liver function. The serum levels of TC, TG,LDL-C, FFA, AST and ALT in HC group were significantly higher than those in NC group (p < 0.05),while HDL-C level was significantly lower (p < 0.05). The serum concentrations of TC, TG, LDL-C, FFA,AST and ALT in HT group were significantly lower than those in HC group (p < 0.05), while HDL-Clevel was significantly higher (p < 0.05). 2.Effects of aerobic exercise on the expression of fatty acidmetabolism regulatory genes in liver of rats. The mRNA expression levels of AMPK, SIRT1 and PGC-1α in liver of HC group were significantly lower than those of NC group (p < 0. 05). While the mRNAexpression levels of AMPK, SIRT1 and PGC-1 α in liver of HT group were significantly higher thanthose of HC group (p < 0. 05).Conclusions Aerobic exercise can improve serum lipid concentration and liver function in NAFLDrats. It increased the consumption of ATP, led to an increase in AMP/ATP ratio, enhanced the mRNAexpression of AMPK, SIRT1 and PGC-1α, activated AMPK - SIRT1 - PGC-1α signaling pathway,reduced hepatic fat synthesis and accelerated fatty acid oxidation in NAFLD rats liver.  


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