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Redox-Unlockable Nanoparticle-Based MST1 Delivery System to Attenuate Hepatic Steatosis via the AMPK/SREBP-1c Signaling Axis.

ABSTRACT: To date, few effective treatments have been licensed for nonalcoholic fatty liver disease (NAFLD), which a kind of chronic liver disease. Mammalian sterile 20-like kinase 1 (MST1) is reported to be involved in the development of NAFLD. Thus, we evaluated the suitability of a redox-unlockable polymeric nanoparticle Hep@PGEA vector to deliver MST1 or siMST1 (HCP/MST1 or HCP/siMST1) for NAFLD therapy. The Hep@PGEA vector can efficiently deliver the condensed functional nucleic acids MST1 or siMST1 into NAFLD-affected mouse liver to upregulate or downregulate MST1 expression. The HCP/MST1 complexes significantly improved liver insulin resistance sensitivity and reduced liver damage and lipid accumulation by the AMPK/SREBP-1c pathway without significant adverse events. Instead, HCP/siMST1 delivery exacerbates the NAFLD. The analysis of NAFLD patient samples further clarified the role of MST1 in the development of hepatic steatosis in patients with NAFLD. The MST1-based gene intervention is of considerable potential for clinical NAFLD therapy, and the Hep@PGEA vector provides a promising option for NAFLD gene therapy.

SUBMITTER: Li Y

PROVIDER: S-EPMC9353777 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Redox-Unlockable Nanoparticle-Based MST1 Delivery System to Attenuate Hepatic Steatosis via the AMPK/SREBP-1c Signaling Axis.

Li Yuhan Y Nie Jing-Jun JJ Yang Yuhui Y Li Jianning J Li Jiarui J Wu Xianxian X Liu Xing X Chen Da-Fu DF Yang Zhiwei Z Xu Fu-Jian FJ Yang Yi Y

ACS applied materials & interfaces 20220720 30

To date, few effective treatments have been licensed for nonalcoholic fatty liver disease (NAFLD), which a kind of chronic liver disease. Mammalian sterile 20-like kinase 1 (MST1) is reported to be involved in the development of NAFLD. Thus, we evaluated the suitability of a redox-unlockable polymeric nanoparticle Hep@PGEA vector to deliver MST1 or siMST1 (HCP/MST1 or HCP/siMST1) for NAFLD therapy. The Hep@PGEA vector can efficiently deliver the condensed functional nucleic acids MST1 or siMST1 ...[more]

PMID: 35858286

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Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, and its incidence is increasing annually, but there is currently no specific drug for treating NAFLD. Shenling Baizhu powder (SL) is a safe herbal compound commonly used in clinical practice. Our previous research has shown that SL has the effect of preventing NAFLD, but its specific mechanism has not been determined. In this study, the potential mechanism of SL on NAFLD was explored by in vivo experiments.MethodsWistar rats fed a choline-deficient amino acid-defined diet (CDAA) were treated with SL for 8 weeks. Then, serum samples were collected to obtain biochemical indicators; adipose tissue and liver samples were collected for pathological detection; a moorFLPI-2 blood flow imager was used to measure liver microcirculation blood flow, and a rat cytokine array was used to screen potential target proteins. The expression of liver adiponectin/SREBP-1c pathway-related proteins was determined by Western blotting.ResultsSL effectively reduced the liver wet weight, as well as the levels of total cholesterol (TC) and triglyceride (TG) in the liver, and ameliorated liver injury in CDAA-fed rats. Pathological examinations showed that SL markedly reduced liver lipid droplets and improved liver lipid accumulation. In addition, the detection of liver blood flow showed that SL increased liver microcirculation in CDAA-fed rats. Through the cytokine array, a differentially expressed cytokine, namely, adiponectin, was screened in the liver. Western blotting assays showed that SL increased the expression of adiponectin and phosphoacetyl-CoA Carboxylase (p-ACC) in the liver and decreased the expression of steroid regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS).ConclusionThese results suggest that SL can increase the levels of adiponectin in the liver and serum and can inhibit the expression of SREBP-1c, thereby regulating systemic lipid metabolism and reducing liver lipid accumulation.

Dataset Information

Redox-Unlockable Nanoparticle-Based MST1 Delivery System to Attenuate Hepatic Steatosis via the AMPK/SREBP-1c Signaling Axis.

Publications

Redox-Unlockable Nanoparticle-Based MST1 Delivery System to Attenuate Hepatic Steatosis via the AMPK/SREBP-1c Signaling Axis.

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