Dataset Information

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy.

ABSTRACT:

Background

Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown.

Methods

To further investigate the effect of FGF1 on diabetic liver injury, we divided db/db mice into two groups and intraperitoneally (i.p.) injected either with FGF1 at 0.5 mg/kg body weight or saline every other day for 4 weeks. Then body weights were measured. Serum and liver tissues were collected for biochemical and molecular analyses.

Results

FGF1 significantly reduced blood glucose and ameliorated diabetes-induced liver steatosis, fibrosis, and apoptosis. FGF1 also restored defective hepatic autophagy in db/db mice. Mechanistic investigations showed that diabetes markedly induced oxidative stress and endoplasmic reticulum stress and that FGF1 treatment significantly attenuated these effects.

Conclusions

FGF1-associated glucose level reduction and amelioration of cellular stress are potential protective effects of FGF1 against diabetes-induced liver injury.

SUBMITTER: Xu Z

PROVIDER: S-EPMC7062965 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy.

Xu Zeping Z Wu Yanqing Y Wang Fan F Li Xiaofeng X Wang Ping P Li Yuying Y Wu Junnan J Li Yiyang Y Jiang Ting T Pan Xindian X Zhang Xie X Xie Longteng L Xiao Jian J Liu Yanlong Y

Frontiers in pharmacology 20200303

<h4>Background</h4>Type 2 diabetes (T2D) is a metabolic dysfunction disease that causes several complications. Liver injury is one of these that severely affects patients with diabetes. Fibroblast growth factor 1 (FGF1) has glucose-lowering activity and plays a role in modulation of several liver injuries. Nevertheless, the effects and potential mechanisms of FGF1 against diabetes-induced liver injury are unknown.<h4>Methods</h4>To further investigate the effect of FGF1 on diabetic liver injury, ...[more]

PMID: 32194395

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Project description:Background and Aims: Acute liver failure (ALF) is a type of liver injury that is caused by multiple factors and leads to severe liver dysfunction; however, current treatments for ALF are insufficient. Magnesium isoglycyrrhizinate (MgIG), a novel glycyrrhizin extracted from the traditional Chinese medicine licorice, has a significant protective effect against concanavalin A (ConA)-induced liver injury, but its underlying therapeutic mechanism is unclear. Hence, this study aims to explore the potential therapeutic mechanism of MgIG against ConA-induced immune liver injury. Methods: ConA (20 mg/kg, i. v.) was administered for 12 h to construct an immune liver injury model, and the treatment group was given MgIG (30 mg/kg, i. p.) injection 1 h in advance. Lethality, liver injury, cytokine levels, and hepatocyte death were evaluated. The level of autophagy was evaluated by electron microscopy, RT-PCR and western blotting, and hepatocyte death was assessed in vitro by flow cytometry. Results: MgIG significantly increased the survival rate of mice and ameliorated severe liver injury mediated by ConA. The decrease in the number of autophagosomes, downregulation of LC3b expression and upregulation of p62 expression indicated that MgIG significantly inhibited ConA-induced autophagy in the liver. Reactivation of autophagy by rapamycin (RAPA) reversed the protective effect of MgIG against ConA-induced liver injury. Compared with MgIG treatment, activation of autophagy by RAPA also promoted the expression of liver inflammation markers (IL-1β, IL-6, TNF-α, CXCL-1, CXCL-2, CXCL-10, etc.) and hepatocyte death. In vitro experiments also showed that MgIG reduced ConA-induced hepatocyte death but did not decrease hepatocyte apoptosis by inhibiting autophagy. Conclusion: MgIG significantly ameliorated ConA-induced immune liver injury in mice by inhibiting autophagy. This study provides theoretical support for the ability of MgIG to protect against liver injury in clinical practice.

Dataset Information

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy.

Background

Methods

Results

Conclusions

Publications

Fibroblast Growth Factor 1 Ameliorates Diabetes-Induced Liver Injury by Reducing Cellular Stress and Restoring Autophagy.

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