Effect of Aruncus dioicus var. kamtschaticus Extract on Neurodegeneration Improvement: Ameliorating Role in Cognitive Disorder Caused by High-Fat Diet Induced Obesity

This study was performed to estimate the possibility of using an ethyl acetate fraction from Aruncus dioicus var. kamtschaticus (EFAD) on metabolic syndrome that is induced by a high-fat diet (HFD). It was demonstrated that EFAD suppresses lipid accumulation and improves insulin resistance (IR) caused by Tumor necrosis factor alpha (TNF-α) in in-vitro experiments using the 3T3-L1 cell. In in-vivo tests, C57BL/6 mice were fed EFAD at 20 and 40 mg/kg body weight (BW) for four weeks after the mice were fed HFD for 15 weeks to induce obesity. EFAD significantly suppressed the elevation of BW and improved impaired glucose tolerance in obese mice. Additionally, this study showed that EFAD has an ameliorating effect on obesity-induced cognitive disorder with behavioral tests. The effect of EFAD on peripheral-IR improvement was confirmed by serum analysis and western blotting in peripheral tissues. Additionally, EFAD showed an ameliorating effect on HFD-induced oxidative stress, impaired cholinergic system and mitochondrial dysfunction, which are interrelated symptoms of neurodegeneration, such as Alzheimer’s disease and central nervous system (CNS)-IR in brain tissue. Furthermore, we confirmed that EFAD improves CNS-IR by confirming the IR-related factors in brain tissue. Consequently, this study suggests the possibility of using EFAD for the prevention of neurodegeneration by improving metabolic syndrome that is caused by HFD.

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Comparison of Efficacy of the Pap and H & E in Identifying the Various Changes in Liver Samples of High Fat Diet Induced Rat - In vitro Study

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i54a33757 ◽

2021 ◽

pp. 364-380

Author(s):

E. Dhivya Sri ◽

R. Priyadharshini ◽

Palati Sinduja ◽

V. Meghashree

Keyword(s):

Metabolic Syndrome ◽

High Fat Diet ◽

In Vitro Study ◽

Signs And Symptoms ◽

Calorie Intake ◽

Control Group ◽

High Fat ◽

Wide Range

Introduction: High fat induced (HFI) liver is associated with a high calorie intake and many other diet-induced complications, such as metabolic syndrome and cardiovascular disease. HFI is the most common chronic liver disease that develops due to high fat intake. A wide range of liver injuries is associated with HFI, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. The signs and symptoms of metabolic syndrome may be induced in rats by feeding them a diet rich in carbohydrates and fat. The aim of the study is Comparison of efficacy of the PAP (Papanicolaou) stain and H&E (Hematoxylin and eosin) stain in identifying the various changes in liver samples of high fat diet induced rat. Materials and Methods: Liver samples of Normal control group animal and High fat diet induced animal were sectioned, weighed fixed 10% neutral buffer formalin and mounted in DPX compound. Four micrometer sections were stained with hematoxylin-eosin and PAP stains for the histological examination of micro-vesicular and macro-vesicular steatosis in the liver tissue. The grading of steatosis was given from 0-3 based on the lipid accumulation (steatosis): grade 0 - absence; grade 1 - mild Steatosis (<30% hepatocyte); grade 2- moderate steatosis (30%-70% hepatocyte); grade3- severe steatosis (>70%hepatocytes). Efficacy of grade of PAP stain and H&E stain were accessed and statistically evaluated by considering seven parameters and overall staining characters where compared. Results: Our present study evaluated high fat induced hepatic steatosis of H&E and PAP stain and also evaluated efficacy of both the stain. In our study, Pie chart showing the percentage distribution of Number of micro-vesicles about 70% represents greater than 30, 10% represents 30-70, 20% represents less than 70 (Fig. 1). In our study 20% represents the greater than 30, 30% represents the 30-70, 50% represents Less than 70 (Fig. 2). 30% represents mild steatosis, 20% represents moderate steatosis, 50% represents Severe Steatosis (Fig. 3). Conclusion: We demonstrated the comparative efficiency of the PAP and H&E high fat diet induced rat liver by in vivo and conclude that both H&E and PAP stain has equal efficacy and clarity in observing the various minute parameters.

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Sequoyitol ameliorates diabetic nephropathy in diabetic rats induced with a high-fat diet and a low dose of streptozotocin

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2013-0307 ◽

2014 ◽

Vol 92 (5) ◽

pp. 405-417 ◽

Cited By ~ 8

Author(s):

Xian-Wei Li ◽

Yan Liu ◽

Wei Hao ◽

Jie-Ren Yang

Keyword(s):

Diabetic Nephropathy ◽

Blood Glucose ◽

High Fat Diet ◽

Low Dose ◽

Serum Insulin ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

High Fat

Sequoyitol decreases blood glucose, improves glucose intolerance, and enhances insulin signaling in ob/ob mice. The aim of this study was to investigate the effects of sequoyitol on diabetic nephropathy in rats with type 2 diabetes mellitus and the mechanism of action. Diabetic rats, induced with a high-fat diet and a low dose of streptozotocin, and were administered sequoyitol (12.5, 25.0, and 50.0 mg·(kg body mass)−1·d−1) for 6 weeks. The levels of fasting blood glucose (FBG), serum insulin, blood urea nitrogen (BUN), and serum creatinine (SCr) were measured. The expression levels of p22phox, p47phox, NF-κB, and TGF-β1 were measured using immunohistochemisty, real-time PCR, and (or) Western blot. The total antioxidative capacity (T-AOC), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) were also determined. The results showed that sequoyitol significantly decreased FBG, BUN, and SCr levels, and increased the insulin levels in diabetic rats. The level of T-AOC was significantly increased, while ROS and MDA levels and the expression of p22phox, p47phox, NF-κB, and TGF-β1 were decreased with sequoyitol treatment both in vivo and in vitro. These results suggested that sequoyitol ameliorates the progression of diabetic nephropathy in rats, as induced by a high-fat diet and a low dose of streptozotocin, through its glucose-lowering effects, antioxidant activity, and regulation of TGF-β1 expression.

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Aloe-Emodin Relieves High-Fat Diet Induced QT Prolongation via MiR-1 Inhibition and IK1 Up-Regulation in Rats

Cellular Physiology and Biochemistry ◽

10.1159/000484120 ◽

2017 ◽

Vol 43 (5) ◽

pp. 1961-1973 ◽

Cited By ~ 11

Author(s):

Yan Bai ◽

Zhenli Su ◽

Hanqi Sun ◽

Wei Zhao ◽

Xue Chen ◽

...

Keyword(s):

Action Potential ◽

Protein Expression ◽

High Fat Diet ◽

Qt Prolongation ◽

Electrical Remodeling ◽

High Fat ◽

Treatment Groups ◽

Aloe Emodin

Background/Aims: High-fat diet (HFD) causes cardiac electrical remodeling and increases the risk of ventricular arrhythmias. Aloe-emodin (AE) is an anthraquinone component isolated from rhubarb and has a similar chemical structure with emodin. The protective effect of emodin against cardiac diseases has been reported in the literature. However, the cardioprotective property of AE is still unknown. The present study investigated the effect of AE on HFD-induced QT prolongation in rats. Methods: Adult male Wistar rats were randomly divided into three groups: control, HFD, and AE-treatment groups. Normal diet was given to rats in the control group, high-fat diet was given to rats in HFD and AE-treatment groups for a total of 10 weeks. First, HFD rats and AE-treatment rats were fed with high-fat diet for 4 weeks to establish the HFD model. Serum total cholesterol and triglyceride levels were measured to validate the HFD model. Afterward, AE-treatment rats were intragastrically administered with 100 mg/kg AE each day for 6 weeks. Electrocardiogram monitoring and whole-cell patch-clamp technique were applied to examine cardiac electrical activity, action potential and inward rectifier K+ current (IK1), respectively. Neonatal rat ventricular myocytes (NRVMs) were subjected to cholesterol and/or AE. Protein expression of Kir2.1 was detected by Western blot and miR-1 level was examined by real-time PCR in vivo and in vitro, respectively. Results: In vivo, AE significantly shortened the QT interval, action potential duration at 90% repolarization (APD90) and resting membrane potential (RMP), which were markedly elongated by HFD. AE increased IK1 current and Kir2.1 protein expression which were reduced in HFD rats. Furthermore, AE significantly inhibited pro-arrhythmic miR-1 in the hearts of HFD rats. In vitro, AE decreased miR-1 expression levels resulting in an increase of Kir2.1 protein levels in cholesterol-enriched NRVMs. Conclusions: AE prevents HFD-induced QT prolongation by repressing miR-1 and upregulating its target Kir2.1. These findings suggest a novel pharmacological role of AE in HFD-induced cardiac electrical remodeling.

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7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6 mice on a high-fat diet

British Journal Of Nutrition ◽

10.1017/s0007114518001824 ◽

2018 ◽

Vol 120 (7) ◽

pp. 751-762 ◽

Cited By ~ 5

Author(s):

Giorgio Biasiotto ◽

Isabella Zanella ◽

Federica Predolini ◽

Ivonne Archetti ◽

Moris Cadei ◽

...

Keyword(s):

Metabolic Syndrome ◽

Body Weight ◽

High Fat Diet ◽

Sugar Metabolism ◽

Lipid Uptake ◽

High Fat ◽

Total Extract ◽

The Metabolic Syndrome ◽

Metabolic Genes

Abstract7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various concentrations in plant foods. The objective of this study was to test HMRLignan™, a purified form of 7-HMR, and the correspondingPicea abiesextract (total extractP. abies; TEP) as dietary supplements on a background of a high-fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3 mg/kg body weight 7-HMR (HMRLignan™) or 10 mg/kg body weight TEP by oral administration. 7-HMR and TEP limited the increase in body weight (−11 and −13 %) and fat mass (−11 and −18 %) in the HFD-fed mice. Epididymal adipocytes were 19 and −12 % smaller and the liver was less steatotic (−62 and −65 %). Serum lipids decreased in TEP-treated mice (−11 % cholesterol, −23 % LDL and −15 % TAG) and sugar metabolism was ameliorated by both lignan preparations, as shown by a more than 70 % decrease in insulin secretion and insulin resistance. The expression of several metabolic genes was modulated by the HFD with an effect that was reversed by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by the inhibited expression of the adipogenic genesPPARγ,C/EBPαandaP2. Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1–6 hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical of the metabolic syndrome and obesity in male mice, whereas their metabolites inhibit adipogenesis and lipid uptakein vitro.

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Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

10.21203/rs.3.rs-775710/v1 ◽

2021 ◽

Author(s):

sheng Qiu ◽

Zerong Liang ◽

Qinan Wu ◽

Miao Wang ◽

Mengliu Yang ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Accumulation ◽

High Fat Diet ◽

Underlying Mechanism ◽

Luciferase Assay ◽

High Fat ◽

Hepatic Lipid ◽

Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

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High-Fat Diet Induced Gut Microbiota Alterations Associating With Ghrelin/Jak2/Stat3 Up-Regulation to Promote Benign Prostatic Hyperplasia Development

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.615928 ◽

2021 ◽

Vol 9 ◽

Author(s):

Meng Gu ◽

Chong Liu ◽

TianYe Yang ◽

Ming Zhan ◽

Zhikang Cai ◽

...

Keyword(s):

Cell Proliferation ◽

Benign Prostatic Hyperplasia ◽

Gut Microbiota ◽

High Fat Diet ◽

Prostatic Hyperplasia ◽

Prostate Tissue ◽

High Fat ◽

Ghrelin Receptor

The role of high-fat diet (HFD) induced gut microbiota alteration and Ghrelin as well as their correlation in benign prostatic hyperplasia (BPH) were explored in our study. The gut microbiota was analyzed by 16s rRNA sequencing. Ghrelin levels in serum, along with Ghrelin and Ghrelin receptor in prostate tissue of mice and patients with BPH were measured. The effect of Ghrelin on cell proliferation, apoptosis, and induction of BPH in mice was explored. Our results indicated that BPH mice have the highest ratio of Firmicutes and Bacteroidetes induced by HFD, as well as Ghrelin level in serum and prostate tissue was significantly increased compared with control. Elevated Ghrelin content in the serum and prostate tissue of BPH patients was also observed. Ghrelin promotes cell proliferation while inhibiting cell apoptosis of prostate cells. The effect of Ghrelin on enlargement of the prostate was found almost equivalent to that of testosterone propionate (TP) which may be attenuated by Ghrelin receptor antagonist YIL-781. Ghrelin could up-regulate Jak2/pJak2/Stat3/pStat3 expression in vitro and in vivo. Our results suggested that Gut microbiota may associate with Ghrelin which plays an important role in activation of Jak2/Stat3 in BPH development. Gut microbiota and Ghrelin might be pathogenic factors for BPH and could be used as a target for mediation.

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The role of 5-HT7 receptors on isoproterenol-induced myocardial infarction in rats with high-fat diet exacerbated coronary endothelial dysfunction

Human & Experimental Toxicology ◽

10.1177/0960327120916821 ◽

2020 ◽

Vol 39 (8) ◽

pp. 1005-1018 ◽

Cited By ~ 1

Author(s):

I Cinar ◽

Z Halici ◽

B Dincer ◽

B Sirin ◽

E Cadirci

Keyword(s):

Myocardial Infarction ◽

Endothelial Dysfunction ◽

High Fat Diet ◽

Density Lipoprotein ◽

Heart Tissue ◽

High Fat ◽

Inflammatory Status

The presence of 5-HT7r’s in both human and rat cardiovascular and immune tissues and their contribution to inflammatory conditions prompted us to hypothesize that these receptors contribute in acute myocardial infarction (MI) with underlying chronic endothelial dysfunction. We investigated the role of 5-HT7 receptors on heart tissue that damaged by isoproterenol (ISO)-induced MI in rats with high-fat diet (HFD). In vitro and in vivo effects of 5-HT7r agonist (LP44) and antagonist (SB269970) have been investigated on the H9C2 cell line and rats, respectively. For in vivo analyses, rats were fed with HFD for 8 weeks and after this period ISO-induced MI model has been applied to rat. To investigate the role of 5-HT7r’s, two different doses of LP44 and SB269970 were evaluated and compared with standard hypolipidemic agent, atorvastatin. In vitro studies showed that LP44 has protective and proliferative effects on rat cardiomyocytes. Also in in vivo studies stimulating 5-HT7r’s by LP44 improved blood lipid profile (decreased total cholesterol, low-density lipoprotein-C, and triglyceride, increased high-density lipoprotein), decreased cardiac damage markers (creatine kinase and troponin-I), and corrected inflammatory status (tumor necrosis factor-α, interleukin-6). Our results showed significant improvement in LP44 administered rats in terms of histopathologic analyses. In damaged tissues, 5-HT7 mRNA expression increased and agonist administration decreased this elevation significantly. We determined for the first time that 5-HT7r’s are overexpressed in ISO-induced MI of rats with underlying HFD-induced endothelial dysfunction. Restoration of this overexpression by LP44, a 5-HT7r agonist, ameliorated heart tissue in physiopathologic, enzymatic, and molecular level, showing the cardiac role of these receptors and suggesting them as future potential therapeutic targets.

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RANKL Is Involved in Runx2-Triggered Hepatic Infiltration of Macrophages in Mice with NAFLD Induced by a High-Fat Diet

BioMed Research International ◽

10.1155/2020/6953421 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Li Zhong ◽

Jianghan Yuan ◽

Lu Huang ◽

Shan Li ◽

Liang Deng

Keyword(s):

High Fat Diet ◽

Macrophage Infiltration ◽

Macrophage Migration ◽

High Fat ◽

Transwell Assay ◽

Nonalcoholic Fatty Liver ◽

Related Transcription Factor

Background. Receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) is significant in the activation of inflammation. Runt-related transcription factor 2 (Runx2) promotes the hepatic infiltration of macrophages in nonalcoholic fatty liver disease (NAFLD). We studied how RANKL affects Runx2-triggered macrophage infiltration in NAFLD. Method. 30 male C57BL/6J mice at 4 weeks of age were utilized in this study, 20 mice received a high-fat diet (HFD), and 10 mice received standard rodent chow over 8 months. The histopathologic features of the liver were identified by H&E, Oil red O, and Masson staining. Runx2, RANKL, and F4/80 were analyzed by western blot, real-time PCR, and immunohistochemistry in vivo, respectively. Lentivirus or siRNA was utilized for transwell assay to investigate the role of RANKL in Runx2-induced macrophage migration in vitro. Results. Compared to controls, during NAFLD development, HFD increased Runx2 and RANKL in vivo in NASH (P<0.01). Meanwhile, a correlation between the expression of Runx2 and RANKL (P<0.05) was evident. In addition, the hepatic infiltration of macrophages was increased upon HFD feeding, and analysis showed that the macrophage infiltration was correlated with the expression of Runx2 or RANKL (P<0.05). In vitro, we found that overexpression or deficiency of Runx2 increased or decreased the production of RANKL in mHSCs. Then, transwell assay revealed that RANKL was involved in Runx2-induced macrophage migration. Conclusions. Overall, RANKL is involved in Runx2-triggered macrophage migration during NAFLD pathogenesis, which may provide an underlying therapeutic target for NAFLD.

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Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes

Royal Society Open Science ◽

10.1098/rsos.170917 ◽

2017 ◽

Vol 4 (11) ◽

pp. 170917 ◽

Cited By ~ 20

Author(s):

Yanyun Pan ◽

Dandan Zhao ◽

Na Yu ◽

Tian An ◽

Jianan Miao ◽

...

Keyword(s):

High Fat Diet ◽

Fasting Blood Glucose ◽

Signalling Pathway ◽

Peroxisome Proliferator ◽

Obese Mice ◽

High Fat ◽

Peroxisome Proliferator Activated Receptor ◽

Glycolipid Metabolism

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.

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