Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phyt...

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Main Authors: Xianghui Huang, Jia Xu, Ye Xu, Bingxin Huangfu, Feng Zhang, Yanzhou Hu, Ruxin Gao, Xinxin Ren, Boyang Zhang, Kunlun Huang, Xiaoyun He
Format: Article
Language:English
Published: Tsinghua University Press 2024-09-01
Series:Food Science and Human Wellness
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Online Access:https://www.sciopen.com/article/10.26599/FSHW.2022.9250220
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author Xianghui Huang
Jia Xu
Ye Xu
Bingxin Huangfu
Feng Zhang
Yanzhou Hu
Ruxin Gao
Xinxin Ren
Boyang Zhang
Kunlun Huang
Xiaoyun He
author_facet Xianghui Huang
Jia Xu
Ye Xu
Bingxin Huangfu
Feng Zhang
Yanzhou Hu
Ruxin Gao
Xinxin Ren
Boyang Zhang
Kunlun Huang
Xiaoyun He
author_sort Xianghui Huang
collection DOAJ
description Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.
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institution Kabale University
issn 2097-0765
2213-4530
language English
publishDate 2024-09-01
publisher Tsinghua University Press
record_format Article
series Food Science and Human Wellness
spelling doaj-art-90b82387882349debc2ab03b94062e072025-01-10T06:56:56ZengTsinghua University PressFood Science and Human Wellness2097-07652213-45302024-09-011352727274010.26599/FSHW.2022.9250220Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarizationXianghui Huang0Jia Xu1Ye Xu2Bingxin Huangfu3Feng Zhang4Yanzhou Hu5Ruxin Gao6Xinxin Ren7Boyang Zhang8Kunlun Huang9Xiaoyun He10Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaKey Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education; College of Food Science and Nutritional Engineering; China Agricultural University, Beijing 100083, ChinaNon-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.https://www.sciopen.com/article/10.26599/FSHW.2022.9250220non-alcoholic steatohepatitis (nash)krüppel-like factor 4nuclear translocationchemokinelipid metabolism
spellingShingle Xianghui Huang
Jia Xu
Ye Xu
Bingxin Huangfu
Feng Zhang
Yanzhou Hu
Ruxin Gao
Xinxin Ren
Boyang Zhang
Kunlun Huang
Xiaoyun He
Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
Food Science and Human Wellness
non-alcoholic steatohepatitis (nash)
krüppel-like factor 4
nuclear translocation
chemokine
lipid metabolism
title Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
title_full Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
title_fullStr Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
title_full_unstemmed Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
title_short Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization
title_sort sulforaphane ameliorates non alcoholic steatohepatitis by klf4 mediated macrophage m2 polarization
topic non-alcoholic steatohepatitis (nash)
krüppel-like factor 4
nuclear translocation
chemokine
lipid metabolism
url https://www.sciopen.com/article/10.26599/FSHW.2022.9250220
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