Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro
Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease...
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2021-12-01
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author | Meng-Hsun Yu Tung-Wei Hung Chi-Chih Wang Sheng-Wen Wu Tzu-Wei Yang Ching-Yu Yang Tsui-Hwa Tseng Chau-Jong Wang |
author_facet | Meng-Hsun Yu Tung-Wei Hung Chi-Chih Wang Sheng-Wen Wu Tzu-Wei Yang Ching-Yu Yang Tsui-Hwa Tseng Chau-Jong Wang |
author_sort | Meng-Hsun Yu |
collection | DOAJ |
description | Neochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid β-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5’ adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway. |
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spelling | doaj.art-7ac34dc23ab2469ba31281c73abe26032023-11-23T02:34:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122231316310.3390/ijms222313163Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In VitroMeng-Hsun Yu0Tung-Wei Hung1Chi-Chih Wang2Sheng-Wen Wu3Tzu-Wei Yang4Ching-Yu Yang5Tsui-Hwa Tseng6Chau-Jong Wang7Institute of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medicine, Division of Nephrology, Chung Shan Medical University Hospital, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medicine, Division of Nephrology, Chung Shan Medical University Hospital, Taichung 40201, TaiwanSchool of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanInstitute of Medicine, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Medical Applied Chemistry, Chung Shan Medical University, Taichung 40201, TaiwanDepartment of Health Industry Technology Management, Chung Shan Medical University, Taichung 40201, TaiwanNeochlorogenic acid (5-Caffeoylquinic acid; 5-CQA), a major phenolic compound isolated from mulberry leaves, possesses anti-oxidative and anti-inflammatory effects. Although it modulates lipid metabolism, the molecular mechanism is unknown. Using an in-vitro model of nonalcoholic fatty liver disease (NAFLD) in which oleic acid (OA) induced lipid accumulation in HepG2 cells, we evaluated the alleviation effect of 5-CQA. We observed that 5-CQA improved OA-induced intracellular lipid accumulation by downregulating sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN) expression, which regulates the fatty acid synthesis, as well as SREBP2 and HMG-CoA reductases (HMG-CoR) expressions, which regulate cholesterol synthesis. Treatment with 5-CQA also increased the expression of fatty acid β-oxidation enzymes. Remarkably, 5-CQA attenuated OA-induced miR-34a expression. A transfection assay with an miR-34a mimic or miR-34a inhibitor revealed that miR-34a suppressed Moreover, Sirtuin 1 (SIRT1) expression and inactivated 5’ adenosine monophosphate-activated protein kinase (AMPK). Our results suggest that 5-CQA alleviates lipid accumulation by downregulating miR-34a, leading to activation of the SIRT1/AMPK pathway.https://www.mdpi.com/1422-0067/22/23/131635-CQANAFLDfatty acid synthesischolesterol synthesismiR-34a |
spellingShingle | Meng-Hsun Yu Tung-Wei Hung Chi-Chih Wang Sheng-Wen Wu Tzu-Wei Yang Ching-Yu Yang Tsui-Hwa Tseng Chau-Jong Wang Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro International Journal of Molecular Sciences 5-CQA NAFLD fatty acid synthesis cholesterol synthesis miR-34a |
title | Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro |
title_full | Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro |
title_fullStr | Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro |
title_full_unstemmed | Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro |
title_short | Neochlorogenic Acid Attenuates Hepatic Lipid Accumulation and Inflammation via Regulating miR-34a In Vitro |
title_sort | neochlorogenic acid attenuates hepatic lipid accumulation and inflammation via regulating mir 34a in vitro |
topic | 5-CQA NAFLD fatty acid synthesis cholesterol synthesis miR-34a |
url | https://www.mdpi.com/1422-0067/22/23/13163 |
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