Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes
Background and purpose: Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332222013415 |
| _version_ | 1811221115745337344 |
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| author | Pu Reun Roh Sung Min Kim Byung-Yoon Kang Kyoung Do Mun Jong Geun Park Min Woo Kang Wonhee Hur Ji Won Han Heechul Nam Seung Kew Yoon Pil Soo Sung |
| author_facet | Pu Reun Roh Sung Min Kim Byung-Yoon Kang Kyoung Do Mun Jong Geun Park Min Woo Kang Wonhee Hur Ji Won Han Heechul Nam Seung Kew Yoon Pil Soo Sung |
| author_sort | Pu Reun Roh |
| collection | DOAJ |
| description | Background and purpose: Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH. Experimental approach: Two different NASH mouse models were established: 1) by subcutaneous injection of streptozotocin (0.2 mg) and feeding the mice a high-fat, high-cholesterol (HFHC) diet, and 2) feeding the mice a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet. Key results: Serum alanine aminotransferase and triglyceride levels in TAF-treated NASH mice were significantly lower than those in the mock-treated ones. The livers from the TAF-treated NASH mice showed attenuated mononuclear phagocyte (MP) infiltration compared to those from the mock-treated ones. TAF-treated NASH mice exhibited decreased liver infiltration of activated MPs (IAIE+/PD-L1+/MerTK+). In ex vivo experiments using sorted human CD14+ monocytes treated with lipopolysaccharide (LPS) and/or TAF, we confirmed the decreased level of phosphorylated AKT in TAF-treated LPS-stimulated monocytes compared to that in the mock-treated ones. Mouse liver immunoblotting showed that phosphorylation levels of AKT were significantly lower in the TAF-treated NASH group than in the mock-treated group. Conclusion and implications: TAF exerts anti-inflammatory effects in NASH livers by attenuating AKT phosphorylation in intrahepatic activated MPs. Therefore, TAF may serve as a new therapeutic option for NASH. |
| first_indexed | 2024-04-12T07:53:42Z |
| format | Article |
| id | doaj.art-cdae4852a10042038630058c32fb5a9b |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-12T07:53:42Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-cdae4852a10042038630058c32fb5a9b2022-12-22T03:41:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-12-01156113952Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytesPu Reun Roh0Sung Min Kim1Byung-Yoon Kang2Kyoung Do Mun3Jong Geun Park4Min Woo Kang5Wonhee Hur6Ji Won Han7Heechul Nam8Seung Kew Yoon9Pil Soo Sung10The Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of KoreaDivision of Viral Disease Research, Center for Infectious Disease Research, Korea National Institute of Health, Chungbuk 28159, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, Uijeongbu 11765, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, Department of Biomedicine & Health Sciences, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul 06591, Republic of Korea; Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea; Corresponding author at: Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Republic of Korea.Background and purpose: Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH. Experimental approach: Two different NASH mouse models were established: 1) by subcutaneous injection of streptozotocin (0.2 mg) and feeding the mice a high-fat, high-cholesterol (HFHC) diet, and 2) feeding the mice a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet. Key results: Serum alanine aminotransferase and triglyceride levels in TAF-treated NASH mice were significantly lower than those in the mock-treated ones. The livers from the TAF-treated NASH mice showed attenuated mononuclear phagocyte (MP) infiltration compared to those from the mock-treated ones. TAF-treated NASH mice exhibited decreased liver infiltration of activated MPs (IAIE+/PD-L1+/MerTK+). In ex vivo experiments using sorted human CD14+ monocytes treated with lipopolysaccharide (LPS) and/or TAF, we confirmed the decreased level of phosphorylated AKT in TAF-treated LPS-stimulated monocytes compared to that in the mock-treated ones. Mouse liver immunoblotting showed that phosphorylation levels of AKT were significantly lower in the TAF-treated NASH group than in the mock-treated group. Conclusion and implications: TAF exerts anti-inflammatory effects in NASH livers by attenuating AKT phosphorylation in intrahepatic activated MPs. Therefore, TAF may serve as a new therapeutic option for NASH.http://www.sciencedirect.com/science/article/pii/S0753332222013415NASH mouse modelPharmacological effectAKTTenofovir alafenamideMononuclear phagocyte |
| spellingShingle | Pu Reun Roh Sung Min Kim Byung-Yoon Kang Kyoung Do Mun Jong Geun Park Min Woo Kang Wonhee Hur Ji Won Han Heechul Nam Seung Kew Yoon Pil Soo Sung Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes Biomedicine & Pharmacotherapy NASH mouse model Pharmacological effect AKT Tenofovir alafenamide Mononuclear phagocyte |
| title | Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes |
| title_full | Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes |
| title_fullStr | Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes |
| title_full_unstemmed | Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes |
| title_short | Tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of AKT in intrahepatic mononuclear phagocytes |
| title_sort | tenofovir alafenamide alleviates nonalcoholic steatohepatitis in mice by blocking the phosphorylation of akt in intrahepatic mononuclear phagocytes |
| topic | NASH mouse model Pharmacological effect AKT Tenofovir alafenamide Mononuclear phagocyte |
| url | http://www.sciencedirect.com/science/article/pii/S0753332222013415 |
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