Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism

Objective To investigate the protective effects of dietary intervention with theaflavin-3, 3'-digallate (TFDG) on liver injury induced by high-fat diet (HFD) in mice and its underlying mechanism. Methods Forty C57BL/6 mice were randomly and equally divided into normal control (NC), model contro...

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Main Authors: ZHANG Gan, FU Hongjuan, ZOU Yixin, DENG Zhihui, CHANG Hui
Format: Article
Language:zho
Published: Editorial Office of Journal of Third Military Medical University 2022-01-01
Series:Di-san junyi daxue xuebao
Subjects:
Online Access:http://aammt.tmmu.edu.cn/Upload/rhtml/202107051.htm
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author ZHANG Gan
FU Hongjuan
ZOU Yixin
DENG Zhihui
CHANG Hui
author_facet ZHANG Gan
FU Hongjuan
ZOU Yixin
DENG Zhihui
CHANG Hui
author_sort ZHANG Gan
collection DOAJ
description Objective To investigate the protective effects of dietary intervention with theaflavin-3, 3'-digallate (TFDG) on liver injury induced by high-fat diet (HFD) in mice and its underlying mechanism. Methods Forty C57BL/6 mice were randomly and equally divided into normal control (NC), model control (MC) and TFDG administration (TF5 and TF10) groups. The mice of the NC group were fed with normal diet, and those of the other 3 groups were given HFD. Then the TF5 and TF10 groups were intragastrically given 5 mg/kg and 10 mg/kg TFDG respectively, while the NC and MC groups were treated with normal saline. After 12 weeks of intervention, the liver index, serum ALT and AST levels were detected, and the pathological changes of liver tissues were observed in the mice. The contents of inflammatory factors and the expression levels of related proteins in liver tissue were determined by ELISA and Western blotting respectively, and the mRNA level of miR-233 was measured by qRT-PCR. Results HFD significantly increased the liver index as well as serum ALT and AST levels, while these changes were effectively reversed by TFDG administration (P < 0.05). Pathological observation displayed that TFDG intervention reduced the formation of lipid droplets in liver tissue, and lipid content detection also suggested that TFDG remarkably declined the levels of triglyceride (TG) and total cholesterol (TC) in liver tissue (P < 0.05). ELISA indicated that the levels of IL-1β, IL-6 and TNF-α were elevated notably in the liver of HFD-fed mice, and Western blotting confirmed higher protein levels of NLRP3, caspase-1 and IL-1β, whereas TFDG inhibited the inflammatory response of liver (P < 0.05) and the activation of NLRP3/IL-1β pathway (P < 0.05). In addition, TFDG intervention greatly up-regulated the expression of miR-223 in the hepatocytes under high-fat condition. After oligonucleotide inhibitor blocked the effect of TFDG on miR-223 expression, its inhibitory effect on inflammatory response was weakened as well (P < 0.05). Conclusion TFDG can effectively alleviate liver injury and inflammatory response induced by HFD, which may be through up-regulation of miR-223 to inhibiting NLRP3 pathway.
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spelling doaj.art-9b01081cb305456eaec5c457cfe2be002022-12-21T19:46:38ZzhoEditorial Office of Journal of Third Military Medical UniversityDi-san junyi daxue xuebao1000-54042022-01-0144214715410.16016/j.2097-0927.202107051Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanismZHANG Gan0FU Hongjuan1ZOU Yixin2DENG Zhihui3 CHANG Hui4College of Food Science, National Experimental Education Demonstration Center for Food Science and Engineering, Southwest University, Chongqing, 400715, China College of Food Science, National Experimental Education Demonstration Center for Food Science and Engineering, Southwest University, Chongqing, 400715, China College of Food Science, National Experimental Education Demonstration Center for Food Science and Engineering, Southwest University, Chongqing, 400715, China College of Food Science, National Experimental Education Demonstration Center for Food Science and Engineering, Southwest University, Chongqing, 400715, China College of Food Science, National Experimental Education Demonstration Center for Food Science and Engineering, Southwest University, Chongqing, 400715, China Objective To investigate the protective effects of dietary intervention with theaflavin-3, 3'-digallate (TFDG) on liver injury induced by high-fat diet (HFD) in mice and its underlying mechanism. Methods Forty C57BL/6 mice were randomly and equally divided into normal control (NC), model control (MC) and TFDG administration (TF5 and TF10) groups. The mice of the NC group were fed with normal diet, and those of the other 3 groups were given HFD. Then the TF5 and TF10 groups were intragastrically given 5 mg/kg and 10 mg/kg TFDG respectively, while the NC and MC groups were treated with normal saline. After 12 weeks of intervention, the liver index, serum ALT and AST levels were detected, and the pathological changes of liver tissues were observed in the mice. The contents of inflammatory factors and the expression levels of related proteins in liver tissue were determined by ELISA and Western blotting respectively, and the mRNA level of miR-233 was measured by qRT-PCR. Results HFD significantly increased the liver index as well as serum ALT and AST levels, while these changes were effectively reversed by TFDG administration (P < 0.05). Pathological observation displayed that TFDG intervention reduced the formation of lipid droplets in liver tissue, and lipid content detection also suggested that TFDG remarkably declined the levels of triglyceride (TG) and total cholesterol (TC) in liver tissue (P < 0.05). ELISA indicated that the levels of IL-1β, IL-6 and TNF-α were elevated notably in the liver of HFD-fed mice, and Western blotting confirmed higher protein levels of NLRP3, caspase-1 and IL-1β, whereas TFDG inhibited the inflammatory response of liver (P < 0.05) and the activation of NLRP3/IL-1β pathway (P < 0.05). In addition, TFDG intervention greatly up-regulated the expression of miR-223 in the hepatocytes under high-fat condition. After oligonucleotide inhibitor blocked the effect of TFDG on miR-223 expression, its inhibitory effect on inflammatory response was weakened as well (P < 0.05). Conclusion TFDG can effectively alleviate liver injury and inflammatory response induced by HFD, which may be through up-regulation of miR-223 to inhibiting NLRP3 pathway.http://aammt.tmmu.edu.cn/Upload/rhtml/202107051.htmtheaflavinnon-alcoholic fatty liver diseaseinflammatory responsemicrorna
spellingShingle ZHANG Gan
FU Hongjuan
ZOU Yixin
DENG Zhihui
CHANG Hui
Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
Di-san junyi daxue xuebao
theaflavin
non-alcoholic fatty liver disease
inflammatory response
microrna
title Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
title_full Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
title_fullStr Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
title_full_unstemmed Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
title_short Effects of theaflavin-3, 3'-digallate on high-fat diet-induced liver injury in mice and its mechanism
title_sort effects of theaflavin 3 3 digallate on high fat diet induced liver injury in mice and its mechanism
topic theaflavin
non-alcoholic fatty liver disease
inflammatory response
microrna
url http://aammt.tmmu.edu.cn/Upload/rhtml/202107051.htm
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