scholarly journals Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet

2016 ◽  
Vol 591 ◽  
pp. 57-65 ◽  
Author(s):  
Stephen L. Slocum ◽  
John J. Skoko ◽  
Nobunao Wakabayashi ◽  
Susan Aja ◽  
Masayuki Yamamoto ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Pathway Activation

Butein induction of HO-1 by p38 MAPK/Nrf2 pathway in adipocytes attenuates high-fat diet induced adipose hypertrophy in mice

2017 ◽  
Vol 799 ◽  
pp. 201-210 ◽  
Author(s):  
Zheng Wang ◽  
Sun-O Ka ◽  
Youngyi Lee ◽  
Byung-Hyun Park ◽  
Eun Ju Bae
Keyword(s):  
P38 Mapk ◽  
High Fat Diet ◽  
High Fat ◽  
Nrf2 Pathway

scholarly journals Digoxin improves steatohepatitis with differential involvement of liver cell subsets in mice through inhibition of PKM2 transactivation

2019 ◽  
Vol 317 (4) ◽  
pp. G387-G397 ◽  
Author(s):  
Peng Zhao ◽  
Sheng-Na Han ◽  
Suyavaran Arumugam ◽  
Muhammad Nadeem Yousaf ◽  
Yanqin Qin ◽  
...  
Keyword(s):  
Liver Injury ◽  
Liver Cell ◽  
Nonalcoholic Steatohepatitis ◽  
High Fat Diet ◽  
Hypoxia Inducible Factor ◽  
Enzyme Activation ◽  
High Fat ◽  
Clinical Applicability ◽  
Pathway Activation ◽  
Differential Involvement

The cardiac glycoside digoxin was identified as a potent suppressor of pyruvate kinase isoform 2-hypoxia-inducible factor-α (PKM2-HIF-1α) pathway activation in liver injury mouse models via intraperitoneal injection. We have assessed the therapeutic effects of digoxin to reduce nonalcoholic steatohepatitis (NASH) by the clinically relevant oral route in mice and analyzed the cellular basis for this effect with differential involvement of liver cell subsets. C57BL/6J male mice were placed on a high-fat diet (HFD) for 10 wk and started concurrently with the gavage of digoxin (2.5, 0.5, 0.125 mg/kg twice a week) for 5 wk. Digoxin significantly reduced HFD-induced hepatic damage, steatosis, and liver inflammation across a wide dosage range. The lowest dose of digoxin (0.125 mg/kg) showed significant protective effects against liver injury and sterile inflammation. Consistently, digoxin attenuated HIF-1α sustained NLRP3 inflammasome activation in macrophages. We have reported for the first time that PKM2 is upregulated in hepatocytes with hepatic steatosis, and digoxin directly improved hepatocyte mitochondrial dysfunction and steatosis. Mechanistically, digoxin directly bound to PKM2 and inhibited PKM2 targeting HIF-1α transactivation without affecting PKM2 enzyme activation. Thus, oral digoxin showed potential to therapeutically inhibit liver injury in NASH through the regulation of PKM2-HIF-1α pathway activation with involvement of multiple cell types. Because of the large clinical experience with oral digoxin, this may have significant clinical applicability in human NASH. NEW & NOTEWORTHY This study is the first to assess the therapeutic efficacy of oral digoxin on nonalcoholic steatohepatitis (NASH) in a high-fat diet (HFD) mouse model and to determine the divergent of cell type-specific effects. Oral digoxin reduced liver damage, steatosis, and inflammation in HFD mice. Digoxin attenuated hypoxia-inducible factor (HIF)-1α axis-sustained inflammasome activity in macrophages and hepatic oxidative stress response in hepatocytes via the regulation of PKM2-HIF-1α axis pathway activation. Oral digoxin may have significant clinical applicability in human NASH.

Low-dose alcohol ameliorated high fat diet-induced anxiety-related behavior via enhancing adiponectin expression and activating the Nrf2 pathway

2021 ◽  
Author(s):  
Jie Cheng ◽  
Meng Zhang ◽  
Shaoli Cheng ◽  
Fan Li ◽  
Bingyi Zhang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Low Dose ◽  
Obese Mice ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Nrf2 Activation

Low-dose alcohol protected HFD-induced obese mice from the augmentation of anxiety-related behavior, which might be related to APN upregulation and Nrf2 activation.

Salvianolic Acid B Inhibits High-Fat Diet-Induced Inflammation by Activating the Nrf2 Pathway

2017 ◽  
Vol 82 (8) ◽  
pp. 1953-1960 ◽  
Author(s):  
Bin Wang ◽  
Jin Sun ◽  
Yonghui Shi ◽  
Guowei Le
Keyword(s):  
High Fat Diet ◽  
Salvianolic Acid B ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Salvianolic Acid

scholarly journals Rosmarinic Acid, the Main Effective Constituent of Orthosiphon stamineus, Inhibits Intestinal Epithelial Apoptosis Via Regulation of the Nrf2 Pathway in Mice

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3027 ◽  
Author(s):  
Xuan Cai ◽  
Fan Yang ◽  
Lihui Zhu ◽  
Ye Xia ◽  
Qingyuan Wu ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
High Fat Diet ◽  
Rosmarinic Acid ◽  
Morphological Characteristics ◽  
Related Factor ◽  
Intestinal Epithelial ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Orthosiphon Stamineus ◽  
Epithelial Cell Apoptosis

Many studies have shown that Orthosiphon stamineus extract (OE) has antioxidant activity, and we previously reported that OE protects the intestine against injury from a high-fat diet. However, the molecular mechanism underlying this protective effect of OE was unclear. Here, OE was separated according to polarity and molecular weight, and the antioxidant activity of each component was compared. The components with the highest antioxidant activity were analyzed by HPLC, which confirmed that rosmarinic acid (RA) was the main effective constituent in OE. OE and RA were then tested in a mouse high-fat diet-induced intestinal injury model. The antioxidant indices and morphological characteristics of the mouse jejunum were measured, and activation of the nuclear factor E2-related factor 2 (Nrf2) pathway and apoptosis of jejunal epithelial cells were analyzed. Of all the constituents in OE, RA contributed the most. Both RA and OE activated the Nrf2 pathway and increased downstream antioxidant enzyme activity. RA and OE protected the mouse intestine against high-fat diet-induced oxidative stress by preventing intestinal epithelial cell apoptosis via both extracellular and intracellular pathways. Thus, RA, the main effective constituent in OE, inhibits intestinal epithelial apoptosis by regulating the Nrf2 pathway in mice.

scholarly journals Polyphenols-Rich Fruit (Euterpe edulis Mart.) Prevents Peripheral Inflammatory Pathway Activation by the Short-Term High-Fat Diet

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1655 ◽  
Author(s):  
Aline Boveto Santamarina ◽  
Giovana Jamar ◽  
Laís Vales Mennitti ◽  
Daniel Araki Ribeiro ◽  
Caroline Margonato Cardoso ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Chow Group ◽  
Control Group ◽  
High Fat ◽  
Inflammatory Pathway ◽  
Inflammatory Parameters ◽  
Pathway Activation ◽  
Freeze Dried

Juçara berry is a potential inflammatory modulator, rich in dietary fiber, fatty acids, and anthocyanins. Considering this, we evaluated the high-fat diet (HFD) intake supplemented with different doses of freeze-dried juçara pulp on the TLR4 pathway. Twenty-seven male Wistar rats with ad libitum access to food and water were divided into four experimental groups: control standard chow group (C); high-fat diet control group (HFC); high-fat diet juçara 0.25% group (HFJ0.25%); and high-fat diet juçara 0.5% group (HFJ0.5%). The inflammatory parameters were analyzed by ELISA and Western blotting in liver and retroperitoneal adipose tissue (RET). The HFJ0.25% group had the energy intake, aspartate transaminase (AST) levels, and liver triacylglycerol accumulation reduced; also, the tumor necrosis factor α (TNF-α) and TNF receptor-associated factor 6 (TRAF6) expression in RET were reduced. However, there were no changes in other protein expressions in liver and adipose tissue. Adiposity and pNFκBp50 had a positive correlation in HFC and HFJ0.5%, but not in the C group and HFJ0.25%. The necrosis hepatic score did not change with treatment; however, the serum (AST) levels and the hepatic triacylglycerol were increased in HFC and HFJ0.5%. These results demonstrated that one week of HFD intake triggered pro-inflammatory mechanisms and liver injury. Additionally, 0.25% juçara prevented inflammatory pathway activation, body weight gain, and liver damage

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