Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH dev...
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doaj-fa0258f1035045639d865f2074aee8f42020-11-25T02:04:06ZengMDPI AGNutrients2072-66432020-05-01121479147910.3390/nu12051479Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in HepatocytesMiori Tanaka0Akari Sato1Yoshimi Kishimoto2Hideaki Mabashi-Asazuma3Kazuo Kondo4Kaoruko Iida5Department of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanDepartment of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanEndowed Research Department “Food for Health”, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanDepartment of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanEndowed Research Department “Food for Health”, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanDepartment of Food and Nutritional Sciences, Graduate School of Humanities and Sciences, Ochanomizu University, 2-1-1 Otsuka, Bunkyo-ku, Tokyo 112-8610, JapanNonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), a natural polyphenol, was reported to exert a protective effect on hepatic steatosis in animal models, but the precise molecular mechanisms remain unclear. Here, we examined the effect of GA on hepatic lipid accumulation, apoptosis, and inflammatory response caused by hepatocyte–macrophage crosstalk. We demonstrated that GA attenuated palmitic acid (PA)-induced fat accumulation via the activation of AMP-activated protein kinase (AMPK) in HepG2 cells. GA also ameliorated cell viability and suppressed apoptosis-related gene expression and caspase 3/7 activity induced by PA and H<sub>2</sub>O<sub>2</sub>. In a co-culture of lipid-laden Hepa 1-6 hepatocytes and RAW 264 macrophages, GA reduced inflammatory mediator expression and induced antioxidant enzyme expression. These results indicate that GA suppresses hepatic lipid accumulation, apoptosis, and inflammation caused by the interaction between hepatocytes and macrophages. The potential effects of GA observed in our study could be effective in preventing NASH and its complications.https://www.mdpi.com/2072-6643/12/5/1479gallic acidpolyphenolnonalcoholic steatohepatitishepatocytemacrophage |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Miori Tanaka Akari Sato Yoshimi Kishimoto Hideaki Mabashi-Asazuma Kazuo Kondo Kaoruko Iida |
spellingShingle |
Miori Tanaka Akari Sato Yoshimi Kishimoto Hideaki Mabashi-Asazuma Kazuo Kondo Kaoruko Iida Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes Nutrients gallic acid polyphenol nonalcoholic steatohepatitis hepatocyte macrophage |
author_facet |
Miori Tanaka Akari Sato Yoshimi Kishimoto Hideaki Mabashi-Asazuma Kazuo Kondo Kaoruko Iida |
author_sort |
Miori Tanaka |
title |
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes |
title_short |
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes |
title_full |
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes |
title_fullStr |
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes |
title_full_unstemmed |
Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes |
title_sort |
gallic acid inhibits lipid accumulation via ampk pathway and suppresses apoptosis and macrophage-mediated inflammation in hepatocytes |
publisher |
MDPI AG |
series |
Nutrients |
issn |
2072-6643 |
publishDate |
2020-05-01 |
description |
Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), a natural polyphenol, was reported to exert a protective effect on hepatic steatosis in animal models, but the precise molecular mechanisms remain unclear. Here, we examined the effect of GA on hepatic lipid accumulation, apoptosis, and inflammatory response caused by hepatocyte–macrophage crosstalk. We demonstrated that GA attenuated palmitic acid (PA)-induced fat accumulation via the activation of AMP-activated protein kinase (AMPK) in HepG2 cells. GA also ameliorated cell viability and suppressed apoptosis-related gene expression and caspase 3/7 activity induced by PA and H<sub>2</sub>O<sub>2</sub>. In a co-culture of lipid-laden Hepa 1-6 hepatocytes and RAW 264 macrophages, GA reduced inflammatory mediator expression and induced antioxidant enzyme expression. These results indicate that GA suppresses hepatic lipid accumulation, apoptosis, and inflammation caused by the interaction between hepatocytes and macrophages. The potential effects of GA observed in our study could be effective in preventing NASH and its complications. |
topic |
gallic acid polyphenol nonalcoholic steatohepatitis hepatocyte macrophage |
url |
https://www.mdpi.com/2072-6643/12/5/1479 |
work_keys_str_mv |
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