Withaferin A Protects Against High-Fat Diet–Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance

2018 ◽  
Vol 188 (1) ◽  
pp. 241-259 ◽  
Author(s):  
Mohamad Hafizi Abu Bakar ◽  
Mohamad Nurul Azmi ◽  
Khairul Anuar Shariff ◽  
Joo Shun Tan
2013 ◽  
Author(s):  
Maya Ramdas ◽  
Chava Harel ◽  
Natalia Krits ◽  
Michal Armoni ◽  
Eddy Karnieli

2019 ◽  
Vol 176 (20) ◽  
pp. 3983-4001 ◽  
Author(s):  
Shengnan Shen ◽  
Qiwen Liao ◽  
Tian Zhang ◽  
Ruile Pan ◽  
Ligen Lin

2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.


2013 ◽  
Vol 41 (03) ◽  
pp. 487-502 ◽  
Author(s):  
Wei-Xi Cui ◽  
Jie Yang ◽  
Xiao-Qing Chen ◽  
Qian Mao ◽  
Xiang-Lan Wei ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.


2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.


2018 ◽  
Vol 19 (10) ◽  
pp. 3281 ◽  
Author(s):  
Youngmi Lee ◽  
Eun-Young Kwon ◽  
Myung-Sook Choi

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.


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