scholarly journals Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation

2018 ◽  
Vol 19 (9) ◽  
pp. 2706 ◽  
Author(s):  
Cristina Sena ◽  
Maria Cipriano ◽  
Maria Botelho ◽  
Raquel Seiça
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Liver Function ◽  
Hepatic Steatosis ◽  
Lipoic Acid ◽  
High Fat Diet ◽  
Control Group ◽  
High Fat ◽  
Tnf Α

Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant α-lipoic acid (α-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (α-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-α (TNF-α) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with α-LA. Plasma and liver tissue MDA and hepatic TNF-α levels were significantly higher in the HFD group when compared with the control group and significantly lower in the α-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with α-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after α-LA treatment. In conclusion, α-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-α and reducing oxidative stress. α-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

scholarly journals Role of TNF-α and FGF-2 in the Fracture Healing Disorder of Type 2 Diabetes Model Induced by High Fat Diet Followed by Streptozotocin

2020 ◽  
Vol Volume 13 ◽  
pp. 2279-2288
Author(s):  
Heqing Huang ◽  
Ling Luo ◽  
Zhitao Liu ◽  
Yan Li ◽  
Zhaochen Tong ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fracture Healing ◽  
High Fat Diet ◽  
High Fat ◽  
Diabetes Model ◽  
Tnf Α

Lactobacillus rhamnosus NCDC17 ameliorates type-2 diabetes by improving gut function, oxidative stress and inflammation in high-fat-diet fed and streptozotocintreated rats

2017 ◽  
Vol 8 (2) ◽  
pp. 243-255 ◽  
Author(s):  
S. Singh ◽  
R.K. Sharma ◽  
S. Malhotra ◽  
R. Pothuraju ◽  
U.K. Shandilya
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Lactobacillus Rhamnosus ◽  
Density Lipoprotein ◽  
Diabetic Rats ◽  
Lipoprotein Cholesterol ◽  
High Fat ◽  
Epididymal Fat

Restoration of dysbiosed gut microbiota through probiotic may have profound effect on type 2 diabetes. In the present study, rats were fed high fat diet (HFD) for 3 weeks and injected with low dose streptozotocin to induce type 2 diabetes. Diabetic rats were then fed Lactobacillus rhamnosus NCDC 17 and L. rhamnosus GG with HFD for six weeks. L. rhamnosus NCDC 17 improved oral glucose tolerance test, biochemical parameters (fasting blood glucose, plasma insulin, glycosylated haemoglobin, free fatty acids, triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol), oxidative stress (thiobarbituric acid reactive substance and activities of catalase, superoxide dismutase and glutathione peroxidase in blood and liver), bifidobacteria and lactobacilli in cecum, expression of glucagon like peptide-1 producing genes in cecum, and adiponection in epididymal fat, while decreased propionate proportions (%) in caecum, and expression of tumour necrosis factor-α and interlukin-6 in epididymal fat of diabetic rats as compared to diabetes control group. These findings offered a base for the use of L. rhamnosus NCDC 17 for the improvement and early treatment of type 2 diabetes.

scholarly journals Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

2016 ◽  
Vol 103 (4) ◽  
pp. 459-468 ◽  
Author(s):  
V Ghorbanzadeh ◽  
M Mohammadi ◽  
G Mohaddes ◽  
H Dariushnejad ◽  
L Chodari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Critical Role ◽  
Diabetic Rats ◽  
Voluntary Exercise ◽  
High Fat ◽  
The Impact ◽  
Type 2 Diabetic

Background Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabetic-associated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

The antianginal ranolazine does not confer beneficial actions against hepatic steatosis in male mice subjected to high-fat diet and streptozotocin induced type 2 diabetes

2021 ◽  
Author(s):  
Christina T Saed ◽  
Amanda A Greenwell ◽  
Seyed Amirhossein Tabatabaei Dakhili ◽  
Keshav Gopal ◽  
Farah Eaton ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Low Fat Diet ◽  
Insulin Tolerance ◽  
Triacylglycerol Content ◽  
Hepatic Triacylglycerol

Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of excess fat in the liver in the absence of alcohol and increases one’s risk for both diabetes and cardiovascular disease (e.g. angina). We have shown that the second-line anti-anginal therapy, ranolazine, mitigates obesity-induced NAFLD, and our aim was to determine whether these actions of ranolazine also extend to NAFLD associated with type 2 diabetes (T2D). 8-week-old male C57BL/6J mice were fed either a low-fat diet or a high-fat diet for 15-weeks, with a single dose of streptozotocin (STZ; 75 mg/kg) administered in the high-fat diet fed mice at 4-weeks to induce experimental T2D. Mice were treated with either vehicle control or ranolazine during the final 7-weeks (50 mg/kg once daily). We assessed glycemia via monitoring glucose tolerance, insulin tolerance, and pyruvate tolerance, whereas hepatic steatosis was assessed via quantifying triacylglycerol content. We observed that ranolazine did not improve glycemia in mice with experimental T2D, while also having no impact on hepatic triacylglycerol content. Therefore, the salutary actions of ranolazine against NAFLD may be limited to obese individuals but not those who are obese with T2D.

scholarly journals Myricitrin Ameliorates Hyperglycemia, Glucose Intolerance, Hepatic Steatosis, and Inflammation in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

2020 ◽  
Vol 21 (5) ◽  
pp. 1870
Author(s):  
Do Yeon Kim ◽  
Sang Ryong Kim ◽  
Un Ju Jung
Keyword(s):  
Mrna Expression ◽  
Hepatic Steatosis ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Diabetic Control ◽  
Control Group ◽  
Diabetic Mice ◽  
High Fat ◽  
Expression And Activity

To test the hypothesis that myricitrin (MYR) improves type 2 diabetes, we examined the effect of MYR on hyperglycemia, glucose intolerance, hepatic steatosis, and inflammation in high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice. Male C57BL/6J mice were randomly divided into three groups: non-diabetic, diabetic control, and MYR (0.005%, w/w)-supplemented diabetic groups. Diabetes was induced by HFD and STZ, and MYR was administered orally for 5 weeks. Myricitrin exerted no significant effects on food intake, body weight, fat weight, or plasma lipids levels. However, MYR significantly decreased fasting blood glucose levels, improved glucose intolerance, and increased pancreatic β-cell mass compared to the diabetic control group. Myricitrin administration also markedly increased glucokinase mRNA expression and activity as well as lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase mRNA expression and activity in the liver. In addition, liver weight, hepatic triglyceride content, and lipid droplet accumulation were markedly decreased following MYR administration. These changes were seemingly attributable to the suppression of the hepatic lipogenic enzymes—fatty acid synthase and phosphatidate phosphohydrolase. Myricitrin also significantly lowered plasma MCP-1 and TNF-α levels and the mRNA expression of hepatic pro-inflammatory genes. These results suggest that MYR has anti-diabetic potential.

scholarly journals SAT-293 Osteocalcin and Exercise Improve Mood and Cognition in Female Mice with High-Fat Diet Induced Type 2 Diabetes

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Jesse Rentz ◽  
Jordan Winberg ◽  
Walter Swardfager ◽  
Jane Mitchell
Keyword(s):  
Type 2 Diabetes ◽  
High Fat Diet ◽  
Treadmill Running ◽  
Control Group ◽  
High Fat ◽  
Low Fat ◽  
Female Mice ◽  
Low Fat Diet ◽  
Metabolic Conditions

Abstract The skeleton has been characterized as an endocrine organ, demonstrating a capacity to modulate cognition, mood and energy homeostasis (1,2). These endocrine actions of the skeleton have been attributed to the osteoblast-derived peptide osteocalcin. In mice, uncarboxylated osteocalcin (ucOCN) decreased the acquisition of type 2 diabetes mellitus (T2DM) and ameliorated depressive- and anxiety-like behaviours (1,2). Clinically, T2DM patients present with reduced serum osteocalcin levels and approximately 1 in 4 also suffer from co-morbid depression (3,4). The cognitive and metabolic benefits of ucOCN are similar to the beneficial effects of exercise that is recommended in treatment of both depression and T2DM. Here we compared the effects of ucOCN or exercise in female C57-BL/6J mice under two different metabolic conditions. Mice were fed either a high-fat diet (60% calories from fat) to induce T2DM or a control diet (10% calories from fat). Groups of mice were either sedentary or exercised daily by 30 min treadmill running for two months, with or without daily administration of ucOCN (30 ng/g/day). Mice with T2DM displayed depressive behaviours marked by a higher immobile time in tail suspension tests compared to control mice (97±25 n=11 vs 207±9.0 s n=12; t21=4.21, P=0.0004). Exercise and osteocalcin both improved depressive behaviour (137±8 n=12; t22=5.85, P&lt;0.0001 & 127±15 s n=12; t22=4.46, P=0.0002). Anxiety, measured by the elevated-plus maze revealed the mice with T2DM displayed increased anxiety spending less time in the open arms and had a lower ratio of open to closed arm entries than the control group (0.37±0.03 n=10 vs 0.21±0.032 n=11; t19=3.56, P=0.0021). Neither exercise nor osteocalcin improved anxiety in the T2DM mice. The puzzle box test revealed the negative effects of the high-fat diet in problem solving and memory, where the sedentary mice displayed greater latencies to solve each task compared to control mice. Exercised and mice receiving osteocalcin displayed performances comparable to that of the control group. Under normal metabolic conditions (low fat diet), neither osteocalcin nor exercise altered responses in any of the behavioural tests. Together, these results: 1. The effects of osteocalcin on behaviour and cognition are comparable to that of the effects of exercise in female mice with T2DM; 2. Behaviour and cognition did not improve from exercise or osteocalcin in female mice on a low-fat diet. References: (1) Ferron et al., Bone. 2012 Feb;50(2):568–575. (2) Oury et al., Cell. 2013 Sep 26:155(1):228–241. (3) Liu et al., Horm Metab Res. 2015 Oct;47(11):813–9. (4) Khaledi et al., Acta Diabetol. 2019 June;56(6):631–650.

scholarly journals Farrerol ameliorates diabetic hepatopathy in rat model of type 2 diabetes mellitus via modulation of oxidativeinflammatory stress

2020 ◽  
Vol 19 (1) ◽  
pp. 71-76
Author(s):  
Li Dong ◽  
Lixia Yang ◽  
Fengsui Liu ◽  
Haitao Zhan ◽  
Xinwei Chen
Keyword(s):  
Diabetes Mellitus ◽  
Normal Control ◽  
High Fat Diet ◽  
Diabetic Control ◽  
Control Group ◽  
High Fat ◽  
Sod Activity ◽  
Treatment Groups ◽  
Tnf Α

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein  cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p < 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p < 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p < 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p < 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p < 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in  humans. Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet

Abresham ameliorates dyslipidemia, hepatic steatosis and hypertension in high-fat diet fed rats by repressing oxidative stress, TNF-α and normalizing NO production

2012 ◽  
Vol 64 (7-8) ◽  
pp. 705-712 ◽  
Author(s):  
Saroj Nepal ◽  
Salma Malik ◽  
Ashok Kumar Sharma ◽  
Saurabh Bharti ◽  
Narender Kumar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
No Production ◽  
High Fat ◽  
Tnf Α
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