HDAC6 inhibitor ACY-1215 protects from nonalcoholic fatty liver disease via inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway

Shifeng Fu; Mengmeng Xu; Jianglei Li; Meihong Yu; Siyi Wang; Liu Han; Rong Li; Feihong Deng; Hailing Peng; Deliang Liu; Yuyong Tan

Heliyon (Jul 2024)

HDAC6 inhibitor ACY-1215 protects from nonalcoholic fatty liver disease via inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway

Shifeng Fu,
Mengmeng Xu,
Jianglei Li,
Meihong Yu,
Siyi Wang,
Liu Han,
Rong Li,
Feihong Deng,
Hailing Peng,
Deliang Liu,
Yuyong Tan

Affiliations

Shifeng Fu: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Mengmeng Xu: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Jianglei Li: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Meihong Yu: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Siyi Wang: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Liu Han: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Rong Li: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Feihong Deng: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China
Hailing Peng: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China; Longshan County People's Hospital, Longshan, 416899, Hunan Province, China
Deliang Liu: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China; Corresponding author. No.139 Renmin Road, Furong district, Changsha city, Hunan province, China.
Yuyong Tan: Department of Gastroenterology, Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan Province, China; Research Center of Digestive Diseases, Central South University, Changsha, 410011, Hunan Province, China; Clinical Research Center of Digestive Diseases of Hunan Province, Changsha, 410011, Hunan Province, China; Corresponding author. No.139 Renmin Road, Furong district, Changsha city, Hunan province, China.

Journal volume & issue: Vol. 10, no. 13
p. e33740

Abstract

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Background & aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. Methods: We established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. Results: ACY-1215 can reduce lipid aggregation, IL-1β, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1βs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. Conclusions: ACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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