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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Main Authors: Meng-Hsun Yu, Tung-Wei Hung, Chi-Chih Wang, Sheng-Wen Wu, Tzu-Wei Yang, Ching-Yu Yang, Tsui-Hwa Tseng, Chau-Jong Wang
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/23/13163
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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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