Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease
Introduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeuti...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1186582/full |
| _version_ | 1797826821189795840 |
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| author | Keungmo Yang Hee-Hoon Kim Young-Ri Shim Tom Ryu Chang Wook Kim |
| author_facet | Keungmo Yang Hee-Hoon Kim Young-Ri Shim Tom Ryu Chang Wook Kim |
| author_sort | Keungmo Yang |
| collection | DOAJ |
| description | Introduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeutic potential in NAFLD. Thus, the present meta-analysis aimed to investigate the efficacy of NAC on NAFLD in preclinical studies.Methods: By searching PubMed, Web of Science, and Cochrane Library, 13 studies were included. The methodological quality was assessed based on the SYstematic Review Centre for Laboratory animal Experimentation guideline, and heterogeneity was evaluated with I2 and p values. Publication bias was assessed by Egger’s test and sensitivity analysis was performed.Results: The results showed that NAC treatment significantly improved systemic and hepatic lipid metabolism (p < 0.01), inflammation-related liver injury (p < 0.01), glucose intolerance (p < 0.05), and hepatic steatosis (p < 0.01) by restoring hepatic glutathione (GSH) (p < 0.05) and GSH reductase (p < 0.05) levels compared to controls in NAFLD-induced animals. Consistently, in bulk, single-cell, and spatial transcriptomics data, the abovementioned target pathways of NAC were strongly associated with NAFLD development in mice and patients.Conclusion: Our study suggests that NAC has therapeutic potential for NAFLD and should be considered for future clinical trials. |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T12:38:23Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-2f77c20a8b084a14b94147ef5caebad62023-05-15T04:38:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-05-011410.3389/fphar.2023.11865821186582Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver diseaseKeungmo Yang0Hee-Hoon Kim1Young-Ri Shim2Tom Ryu3Chang Wook Kim4Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaLife Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaLife Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaDepartment of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Republic of KoreaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaIntroduction: The continuous rise in the prevalence of nonalcoholic fatty liver disease (NAFLD) is emerging as a global health issue. Although the protective effects of N-acetylcysteine (NAC), an antioxidant, against various diseases have been reported, it is still unclear whether NAC has therapeutic potential in NAFLD. Thus, the present meta-analysis aimed to investigate the efficacy of NAC on NAFLD in preclinical studies.Methods: By searching PubMed, Web of Science, and Cochrane Library, 13 studies were included. The methodological quality was assessed based on the SYstematic Review Centre for Laboratory animal Experimentation guideline, and heterogeneity was evaluated with I2 and p values. Publication bias was assessed by Egger’s test and sensitivity analysis was performed.Results: The results showed that NAC treatment significantly improved systemic and hepatic lipid metabolism (p < 0.01), inflammation-related liver injury (p < 0.01), glucose intolerance (p < 0.05), and hepatic steatosis (p < 0.01) by restoring hepatic glutathione (GSH) (p < 0.05) and GSH reductase (p < 0.05) levels compared to controls in NAFLD-induced animals. Consistently, in bulk, single-cell, and spatial transcriptomics data, the abovementioned target pathways of NAC were strongly associated with NAFLD development in mice and patients.Conclusion: Our study suggests that NAC has therapeutic potential for NAFLD and should be considered for future clinical trials.https://www.frontiersin.org/articles/10.3389/fphar.2023.1186582/fullnonalcoholic fatty liver diseaseN-acetylcysteinemeta-analysislipid metabolismglutathioneinflammation |
| spellingShingle | Keungmo Yang Hee-Hoon Kim Young-Ri Shim Tom Ryu Chang Wook Kim Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease Frontiers in Pharmacology nonalcoholic fatty liver disease N-acetylcysteine meta-analysis lipid metabolism glutathione inflammation |
| title | Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease |
| title_full | Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease |
| title_fullStr | Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease |
| title_full_unstemmed | Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease |
| title_short | Comprehensive transcriptomic analysis and meta-analysis identify therapeutic effects of N-acetylcysteine in nonalcoholic fatty liver disease |
| title_sort | comprehensive transcriptomic analysis and meta analysis identify therapeutic effects of n acetylcysteine in nonalcoholic fatty liver disease |
| topic | nonalcoholic fatty liver disease N-acetylcysteine meta-analysis lipid metabolism glutathione inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1186582/full |
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