Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis
Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the abi...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1148814/full |
| _version_ | 1797866875748614144 |
|---|---|
| author | Shi-Bin Ding Xiao-Lei Chu Yu-Xuan Jin Jin-Jin Jiang Xiao Zhao Min Yu |
| author_facet | Shi-Bin Ding Xiao-Lei Chu Yu-Xuan Jin Jin-Jin Jiang Xiao Zhao Min Yu |
| author_sort | Shi-Bin Ding |
| collection | DOAJ |
| description | Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice.Methods: Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. In vitro, steatotic L-02 cells were used to explore the underlying mechanism.Results: In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells.Conclusion: Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes. |
| first_indexed | 2024-04-09T23:31:18Z |
| format | Article |
| id | doaj.art-e51f119500214d00995a9b046e60e201 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-09T23:31:18Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e51f119500214d00995a9b046e60e2012023-03-21T05:26:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.11488141148814Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosisShi-Bin DingXiao-Lei ChuYu-Xuan JinJin-Jin JiangXiao ZhaoMin YuBackground: Non-alcoholic fatty liver disease (NAFLD) is a chronic advanced liver disease that is highly related to metabolic disorders and induced by a high-fat diet (HFD). Recently, epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea that has the ability to protect against non-alcoholic fatty liver disease, but the molecular mechanism remains poorly deciphered. Ferroptosis plays a vital role in the progression of non-alcoholic fatty liver disease, but experimental evidence of ferroptosis inhibition by epigallocatechin gallate is limited. Hence, our study aimed to investigate the effect and mechanisms of epigallocatechin gallate on hepatic ferroptosis to mitigate hepatic injury in high-fat diet-fed mice.Methods: Fifty male C57BL/6 mice were fed either a standard chow diet (SCD), a high-fat diet, or a high-fat diet and administered epigallocatechin gallate or ferrostatin-1 (a ferroptosis-specific inhibitor) for 12 weeks. Liver injury, lipid accumulation, hepatic steatosis, oxidative stress, iron overload, and ferroptosis marker proteins were examined. In vitro, steatotic L-02 cells were used to explore the underlying mechanism.Results: In our research, we found that epigallocatechin gallate notably alleviated liver injury and lipid accumulation, oxidative stress, hepatic steatosis, decreased iron overload and inhibited ferroptosis in a high-fat diet-induced murine model of non-alcoholic fatty liver disease. In vitro experiments, using ferrostatin-1 and a mitochondrial reactive oxygen species (MtROS) scavenger (Mito-TEMPO), we found that epigallocatechin gallate remarkably alleviated oxidative stress and inhibited ferroptosis by reducing the level of mitochondrial reactive oxygen species in steatotic L-02 cells.Conclusion: Taken together, our results revealed that epigallocatechin gallate may exert protective effects on hepatic lipotoxicity by inhibiting mitochondrial reactive oxygen species-mediated hepatic ferroptosis. Findings from our study provide new insight into prevention and treatment strategies for non-alcoholic fatty liver disease pathological processes.https://www.frontiersin.org/articles/10.3389/fphar.2023.1148814/fullepigallocatechin gallatemitochondrial ROSferroptosishigh-fat diethepatic lipotoxicity |
| spellingShingle | Shi-Bin Ding Xiao-Lei Chu Yu-Xuan Jin Jin-Jin Jiang Xiao Zhao Min Yu Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis Frontiers in Pharmacology epigallocatechin gallate mitochondrial ROS ferroptosis high-fat diet hepatic lipotoxicity |
| title | Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis |
| title_full | Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis |
| title_fullStr | Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis |
| title_full_unstemmed | Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis |
| title_short | Epigallocatechin gallate alleviates high-fat diet-induced hepatic lipotoxicity by targeting mitochondrial ROS-mediated ferroptosis |
| title_sort | epigallocatechin gallate alleviates high fat diet induced hepatic lipotoxicity by targeting mitochondrial ros mediated ferroptosis |
| topic | epigallocatechin gallate mitochondrial ROS ferroptosis high-fat diet hepatic lipotoxicity |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1148814/full |
| work_keys_str_mv | AT shibinding epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis AT xiaoleichu epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis AT yuxuanjin epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis AT jinjinjiang epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis AT xiaozhao epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis AT minyu epigallocatechingallatealleviateshighfatdietinducedhepaticlipotoxicitybytargetingmitochondrialrosmediatedferroptosis |