Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

Li, Yongmei; Zhang, Yuan; Ji, Guang; Shen, Yiwei; Zhao, Nan; Liang, Yuhan; Wang, Zihan; Liu, Mengqi; Lin, Li‐Rong

doi:10.1155/2020/6181630

Cited by 22 publications

(22 citation statements)

References 46 publications

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“…LC3 (microtubule-associated protein light chain 3, MAP LC3) was the first autophagosome marker protein to be identified in mammals and is homologous to the yeast autophagy-related gene Atg8. Similar to previous studies, SD has been shown to cause excessive levels of autophagy and may be one of the causes of impairment of learning and memory (8,29,30).…”

Section: Discussionsupporting

confidence: 83%

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy

Dai¹,

Xiao²,

Tu³

et al. 2021

Ann Transl Med

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Background: Sleep deprivation (SD) causes a disturbance in the cognitive function of rats. While propofol has a powerful sedative and hypnotic effect and is an antioxidant, its effect on the cognitive function of rats following SD remains unknown. The purpose of this study was to explore the protective effects of propofol on excessive autophagy and mitophagy in the hippocampus of rats after SD.Methods: Adult male rats were intraperitoneally injected with 30 mg/kg of propofol after 96 hours of SD.Then we evaluated the effect of propofol on the cognitive function of sleep deprived rats by the Morris water maze. Transmission electron microscopy, Western blotting, PCR, immunohistochemistry, autophagy enhancer and autophagy inhibitor were used to study the effect of propofol on hippocampal neurons of rat with excessive autophagy and mitophagy. Results:The behavioral experimental results of the Morris water maze showed that propofol improved the learning and memory ability of sleep-deprived rats. The expression of Beclin1, PINK1, parkin, p62, and LC3 protein increased significantly after sleep deprivation. While the intervention of propofol could significantly reduce the expression of these proteins, rapamycin treatment eliminated this effect.Conclusions: Our findings showed that propofol could reduce the impairment of learning and memory in sleep-deprived rats by inhibiting excessive autophagy and mitophagy in hippocampal neurons. This strategy may provide an application basis for the clinical use of propofol in patients with chronic insomnia.

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Section: Discussionsupporting

confidence: 83%

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy

Dai¹,

Xiao²,

Tu³

et al. 2021

Ann Transl Med

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“…Previous studies have demonstrated that the excessive lipid accumulation can lead to cellular injury and death (Czaja, 2016;Li et al, 2020). In this study, we focused on the effects of dapagliflozin on hepatic steatosis and explored the relevant mechanism using hepatic cells and ZDF rats with obesity, NAFLD and metabolic dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway

Huang

et al. 2021

Front. Pharmacol.

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As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis in vitro and in vivo. We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both in vitro and in vivo. In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid β-oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.

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“…Furthermore, POMC is one of the target genes of mTOR in the CNS (Cota et al, 2006). A recent study found that sleep deprivation could induce oxidative stress mediated by the AKT/mTOR signaling pathway in the liver of rats (Li et al, 2020). Our study is the first to highlight mTOR signaling dysfunction in the hypothalamus of chronically sleep-restricted rats.…”

Section: Discussionmentioning

confidence: 55%

Chronic Timed Sleep Restriction Attenuates LepRb-Mediated Signaling Pathways and Circadian Clock Gene Expression in the Rat Hypothalamus

et al. 2020

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The sleep duration of adolescents has continued to decline over the past 20 years. Sleep insufficiency is one of the most important risk factors for obesity, but the mechanisms underlying the association are unclear. Therefore, the hypothalamic-regulated mechanisms of appetite and the circadian clock gene expression were examined in sleep-restricted rats. Rats aged 7 weeks were randomly divided into two groups: the control group and sleep restriction group (7 rats/group) rats were sleep-restricted for 4 weeks. Body weight gain and amount of food/water consumption were quantified. The expression of genes or proteins which regulated appetite and energy metabolism via leptin receptor signaling and the circadian clock in the hypothalamus were assessed. Chronic sleep restriction induced increased food intake and weight gain in adolescent and young adult rats from the second week of initiation of sleep restriction. Phosphorylation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) was decreased, although levels of circulating leptin or leptin receptor expression were unaltered. Furthermore, insulin receptor substrate (IRS)/phosphoinositide 3-kinase (PI3K)/AKT/mTOR and forkhead box O1 (FoxO1) signaling pathways were also compromised. Moreover, core circadian clock genes were also decreased in the sleep restriction group compared with the control. Chronic timed sleep restriction induced hyperphagic behaviors, attenuated leptin receptor-mediated signaling pathways, and depleted the expression of circadian clock gene in the hypothalamus of adolescent and young adult rats.

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Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats

Cited by 22 publications

References 46 publications

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy

Propofol protects hippocampal neurons in sleep-deprived rats by inhibiting mitophagy and autophagy

Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway

Chronic Timed Sleep Restriction Attenuates LepRb-Mediated Signaling Pathways and Circadian Clock Gene Expression in the Rat Hypothalamus

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