scholarly journals Protective Effects of MitoTEMPO on Nonalcoholic Fatty Liver Disease via Regulating Myeloid-Derived Suppressor Cells and Inflammation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jiayuan Wu ◽  
Li Zheng ◽  
Juanfen Mo ◽  
Xiujuan Yao ◽  
Chenliang Fan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Calcium Binding ◽  
Fatty Liver Disease ◽  
Calcium Binding Protein ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
S100 Calcium Binding Protein ◽  
Protein Expressions

MitoTEMPO, a mitochondrial antioxidant, has protective effects on liver-related diseases. However, the role of MitoTEMPO on nonalcoholic fatty liver disease (NAFLD) and its possible mechanisms are largely unknown. Here, we investigated the effects of MitoTEMPO on NAFLD using high fat diet- (HFD-) induced obese mice as animal models. MitoTEMPO was intraperitoneally injected into HFD mice. Liver morphological changes were observed by H&E and Oil Red O staining, and the frequency of MDSCs in peripheral blood was analyzed by flow cytometry. Moreover, real-time quantitative PCR, western blot, and immunohistochemistry were conducted to detect the mRNA and protein expressions in the liver tissues. The results showed that the hepatic steatosis in liver tissues of HFD mice injected with MitoTEMPO was significantly ameliorated. Additionally, MitoTEMPO reduced the frequency of CD11b+Gr-1+ MDSCs in peripheral circulation and decreased Gr-1+ cell accumulation in the livers. Further studies demonstrated that MitoTEMPO administration suppressed the mRNA and protein expressions of MDSC-associated proinflammatory mediators, such as monocyte chemoattractant protein-1 (MCP-1), S100 calcium-binding protein A8 (S100A8), and S100 calcium-binding protein A9 (S100A9). Our results suggest that MitoTEMPO appears to be a potential chemical compound affecting certain immune cells and further ameliorates inflammation in obese-associated NAFLD.

Polyphenol intakes and risk of impaired lipid profile, elevated hepatic enzymes and nonalcoholic fatty liver disease

2019 ◽  
Vol 49 (5) ◽  
pp. 903-910 ◽  
Author(s):  
Mehrnaz Nikkhah-Bodaghi ◽  
Matin Ghanavati ◽  
Azita Hekmatdoost
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Separate Analysis ◽  
Protective Effects ◽  
Hepatic Enzymes ◽  
Content Type ◽  
Nonalcoholic Fatty Liver

PurposePolyphenols are plant-derived bioactive compounds with some known hepato-protective effects. The purpose of this study is to evaluate the association between polyphenol consumption and risk of nonalcoholic fatty liver disease (NAFLD) and its related conditions such as impaired lipid profile and elevated hepatic enzymes.Design/methodology/approachA total of 196 NAFLD patients and 803 controls were enrolled in this case-control study. Biochemical and anthropometric measurements as well as polyphenol consumption during the previous year were assessed.FindingsIn unadjusted model, participants who consumed the third and fourth quartiles of polyphenols intake were less likely to have NAFLD in comparison to those who consumed the first quartile [odds ratio, OR: 0.48; 95 per cent confidence interval, CI: (0.30-0.77) and OR: 0.62; 95 per cent CI: (0.40-0.96), respectively]. In separate analysis of genders, this effect was seen only in male participants [OR: 0.29; 95 per cent CI: (0.14-0.58) and OR: 0.21; 95 per cent CI (0.10-0.42), respectively], and the association remained significant after adjustment for energy, body mass index, age and smoking.Originality/valueHigher total polyphenol intake is associated with a decreased risk of NAFLD. Prospective studies are needed to confirm these results.

Hepatic AMP Kinase as a Potential Target for Treating Nonalcoholic Fatty Liver Disease: Evidence from Studies of Natural Products

2018 ◽  
Vol 25 (8) ◽  
pp. 889-907 ◽  
Author(s):  
Gang Xu ◽  
Kaixun Huang ◽  
Jun Zhou
Keyword(s):  
Natural Products ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Adenosine Monophosphate ◽  
Protective Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling ◽  
Downstream Effectors

Background: Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is the leading cause of cryptogenic cirrhosis and has consistently been implicated in related metabolic disorders, such as dyslipidemia and type 2 diabetes (T2D). However, the pathogenesis of NAFLD remains to be elucidated, and no established therapeutic regimens for treating NAFLD exist. Adenosine monophosphate (AMP)-activated protein kinase (AMPK), the main cellular energy sensor, has been implicated as a key regulator of hepatic lipid and glucose metabolism. Recently, emerging evidence indicates that many plant-derived natural products are capable of ameliorating NAFLD by targeting AMPK. Methods: The published literature in PubMed relating to this topic was searched through June 2016. Results: Significant advances have been made with respect to understanding the protective effects of plant-derived natural products against NAFLD. A variety of natural products, including alkaloids (berberine, demethyleneberberine, nicotine, caffeine, etc.), polyphenols (resveratrol, puerarin, curcumin, caffeic acid, etc.) and other compounds (β- caryophyllene, gastrodin, compound K, betulinic acid, etc.), have demonstrated promising results in preclinical studies. Mechanistic studies of these compounds have focused on their activation of AMPK and its downstream effectors involved in lipid metabolism. Conclusion: The findings of this review confirm that plant-derived natural products capable of activating the AMPK signaling pathway are potential therapeutic agents for NAFLD.

scholarly journals Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 55
Author(s):  
Tingyi Du ◽  
Qin Fang ◽  
Zhihao Zhang ◽  
Chuanmeng Zhu ◽  
Renfan Xu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Chow Diet ◽  
Protective Effects ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

Aim: Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. Methods: C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 μM palmitate acid (PA) with or without LNT (5 μg/mL). Results: After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. Conclusion: In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

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