D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease

Hu, Mengyao; Chen, Yu; Deng, Fan; Chang, Bo Yoon; Luo, Jialiang; Dong, Lijun; Xiao, Lü; Zhang, Yi; Chen, Zhengliang; Zhou, Jia

doi:10.3389/fimmu.2022.877650

Cited by 16 publications

(11 citation statements)

References 73 publications

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“…In addition, ethanol up−regulates CYP2E1, resulting in increased oxidative stress, which can also inhibit PPARα [ 49 ]. Mengyao Hu et al determined D−mannose regulates abnormal lipid metabolism in ALD by inhibiting the expression of SREBP1c, ACC1, and FASN [ 50 ]. In our experiment, DAU reduced the increase of hepatic TG and FFA induced by alcohol and significantly inhibited the lipid synthesis gene SREBP1c, FASN, and SCD1.…”

Section: Discussionmentioning

confidence: 99%

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

et al. 2023

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Alcoholic liver disease (ALD) is caused by chronic excessive alcohol consumption, which leads to inflammation, oxidative stress, lipid accumulation, liver fibrosis/cirrhosis, and even liver cancer. However, there are currently no effective drugs for ALD. Herein, we report that a natural phytosterol Daucosterol (DAU) can effectively protect against liver injury caused by alcohol, which plays anti−inflammatory and antioxidative roles in many chronic inflammatory diseases. Our results demonstrate that DAU ameliorates liver inflammation induced by alcohol through p38/nuclear factor kappa B (NF−κB)/NOD−like receptor protein−3 (NLRP3) inflammasome pathway. Briefly, DAU decreases NF−κB nuclear translocation and inhibits NLRP3 activation by decreasing p38 phosphorylation. At the same time, DAU also protects against hepatic oxidative stress and lipid accumulation. In conclusion, our research provides a new clue about the protective effects of naturally active substances on ALD.

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Section: Discussionmentioning

confidence: 99%

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

et al. 2023

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“…The activation of AKT is involved in GPR43 expression in many cell types. , A study in mice showed that enhanced insulin secretion mediated by upregulating GPR43 expression is dependent on PI3K/AKT activation . SCFAs can activate the PI3K/AKT signaling pathway in mice .…”

Section: Discussionmentioning

confidence: 99%

Acetate Upregulates GPR43 Expression and Function via PI3K-AKT-SP1 Signaling in Mammary Epithelial Cells during Milk Fat Synthesis

Yang,

Liu,

Zhang

et al. 2023

J. Agric. Food Chem.

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This study investigated the mechanism underlying acetate-induced orphan G-protein-coupled receptor 43 (GPR43) expression and milk fat production. The mammary epithelial cells of dairy cows were treated with acetate, and the effects of GPR43 on acetate uptake and the expression of lipogenesis-related genes were determined by gas chromatography and quantitative polymerase chain reaction (qPCR), respectively. RNAi, inhibitor treatment, and luciferase assay were used to determine the effect of phosphoinositide 3-kinase-protein kinase B-specificity protein 1 (PI3K-AKT-SP1) signaling on acetate-induced GPR43 expression and function. The results showed that GPR43 was highly expressed in lactating cow mammary tissues, which was related to milk fat synthesis. 12 mM acetate significantly increased the GPR43 expression in mammary epithelial cells of dairy cows. In acetate-treated cells, GPR43 overexpression significantly increased the cellular uptake of acetate, the intracellular triacylglycerol (TAG) content, and acetate-induced lipogenesis gene expression. Acetate activated PI3K-AKT signaling and promoted SP1 translocation from the cytosol into the nucleus, where SP1 bound to the GPR43 promoter and upregulated GPR43 transcription. Moreover, the activation of PI3K-AKT-SP1 by acetate facilitated the trafficking of GPR43 from the cytosol to the plasma membrane. In conclusion, acetate upregulated GPR43 expression and function via PI3K-AKT-SP1 signaling in mammary epithelial cells, thereby increasing milk fat synthesis. These results provide an experimental strategy for improving milk lipid synthesis, which is important to the dairy industry.

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“…Research on the PI3K/PTEN/Akt signaling pathway has also shown its involvement in alcohol-induced liver injury [89,90]. Inhibition of PTEN lipid phosphatase activity led to an increase in Akt activity.…”

Section: Oxidative Inactivation Of Pten In Aldmentioning

confidence: 99%

The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease

et al. 2023

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Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are becoming increasingly prevalent worldwide. Despite the different etiologies, their spectra and histological feature are similar, from simple steatosis to more advanced stages such as steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Studies including peroxiredoxin knockout models revealed that oxidative stress is crucial in these diseases, which present as consequences of redox imbalance. Protein tyrosine phosphatases (PTPs) are a superfamily of enzymes that are major targets of reactive oxygen species (ROS) because of an oxidation-susceptible nucleophilic cysteine in their active site. Herein, we review the oxidative inactivation of two tumor suppressor PTPs, phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and T-cell protein tyrosine phosphatase (TCPTP), and their contribution to the pathogenicity of ALD and NAFLD, respectively. This review might provide a better understanding of the pathogenic mechanisms of these diseases and help develop new therapeutic strategies to treat fatty liver disease.

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D-Mannose Regulates Hepatocyte Lipid Metabolism via PI3K/Akt/mTOR Signaling Pathway and Ameliorates Hepatic Steatosis in Alcoholic Liver Disease

Cited by 16 publications

References 73 publications

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

Daucosterol Alleviates Alcohol−Induced Hepatic Injury and Inflammation through P38/NF−κB/NLRP3 Inflammasome Pathway

Acetate Upregulates GPR43 Expression and Function via PI3K-AKT-SP1 Signaling in Mammary Epithelial Cells during Milk Fat Synthesis

The Role of Oxidative Inactivation of Phosphatase PTEN and TCPTP in Fatty Liver Disease

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