Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis

Baoqing Liu,1 Xiaoxiang Mao,2,3 Dandan Huang,2,3 Fei Li,1 Nianguo Dong11Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Liu B, Mao X, Huang D, Li F, Dong N
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	metabolic homeostasis starvation stress NLRP3 MCC950 SREBP-1c Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/5b37ca73dbc0437a8b6f58ee6a1b66fe
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5b37ca73dbc0437a8b6f58ee6a1b66fe
record_format	dspace
spelling	oai:doaj.org-article:5b37ca73dbc0437a8b6f58ee6a1b66fe2021-12-02T09:59:09ZNovel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis1178-7007https://doaj.org/article/5b37ca73dbc0437a8b6f58ee6a1b66fe2019-05-01T00:00:00Zhttps://www.dovepress.com/novel-role-of-nlrp3-inflammasome-in-regulation-of-lipogenesis-in-fasti-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Baoqing Liu,1 Xiaoxiang Mao,2,3 Dandan Huang,2,3 Fei Li,1 Nianguo Dong11Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaBackground: The liver coordinates a series of metabolic adaptations to maintain the energy balance of the system and provide adequate nutrients to key organs, tissues and cells during starvation. However, the mediators and underlying molecular mechanisms that mediate these fasting-induced adaptive responses remain unclear.Materials and methods: Male wild-type C57BL/6J littermates (8-weeks-old) were intraperitoneally injected with MCC950 or vehicle, and then randomly divided into three groups: fed, fasted, and refed. Plasma IL1β and insulin levels were detected by ELISA kits. Plasma and hepatic metabolites were determined using commercial assay kits. HepaRG cell line was applied to verify the regulation of NLRP3 on lipogenesis.Results: NOD-like receptor protein 3 (NLRP3) and its downstream inflammatory cytokines were significantly suppressed after 24 h fasting and recovered upon 6 h refeeding in plasma and liver tissues of mice. Moreover, fasting-induced hepatic steatosis and accompanied liver injury were ameliorated when mice were intraperitoneally injected with MCC950 (a selective NLRP3 inhibitor). Further study revealed that MCC950 suppressed sterol regulatory element-binding protein-1c (SREBP-1c) expression and transcriptional activity, thus inhibited lipogenesis in the liver, which may explain its role in stabilizing lipid metabolism.Conclusion: The NLRP3 inhibitor-MCC950 protects against fasting-induced hepatic steatosis. The novel and critical role of NLRP3 in lipogenesis may explain its importance in regulating the adaptive responses of the liver upon starvation stress and may provide therapeutic value.Keywords: metabolic homeostasis, starvation stress, NLRP3, MCC950, SREBP-1cLiu BMao XHuang DLi FDong NDove Medical Pressarticlemetabolic homeostasisstarvation stressNLRP3MCC950SREBP-1cSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 12, Pp 801-811 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	metabolic homeostasis starvation stress NLRP3 MCC950 SREBP-1c Specialties of internal medicine RC581-951
spellingShingle	metabolic homeostasis starvation stress NLRP3 MCC950 SREBP-1c Specialties of internal medicine RC581-951 Liu B Mao X Huang D Li F Dong N Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
description	Baoqing Liu,1 Xiaoxiang Mao,2,3 Dandan Huang,2,3 Fei Li,1 Nianguo Dong11Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaBackground: The liver coordinates a series of metabolic adaptations to maintain the energy balance of the system and provide adequate nutrients to key organs, tissues and cells during starvation. However, the mediators and underlying molecular mechanisms that mediate these fasting-induced adaptive responses remain unclear.Materials and methods: Male wild-type C57BL/6J littermates (8-weeks-old) were intraperitoneally injected with MCC950 or vehicle, and then randomly divided into three groups: fed, fasted, and refed. Plasma IL1β and insulin levels were detected by ELISA kits. Plasma and hepatic metabolites were determined using commercial assay kits. HepaRG cell line was applied to verify the regulation of NLRP3 on lipogenesis.Results: NOD-like receptor protein 3 (NLRP3) and its downstream inflammatory cytokines were significantly suppressed after 24 h fasting and recovered upon 6 h refeeding in plasma and liver tissues of mice. Moreover, fasting-induced hepatic steatosis and accompanied liver injury were ameliorated when mice were intraperitoneally injected with MCC950 (a selective NLRP3 inhibitor). Further study revealed that MCC950 suppressed sterol regulatory element-binding protein-1c (SREBP-1c) expression and transcriptional activity, thus inhibited lipogenesis in the liver, which may explain its role in stabilizing lipid metabolism.Conclusion: The NLRP3 inhibitor-MCC950 protects against fasting-induced hepatic steatosis. The novel and critical role of NLRP3 in lipogenesis may explain its importance in regulating the adaptive responses of the liver upon starvation stress and may provide therapeutic value.Keywords: metabolic homeostasis, starvation stress, NLRP3, MCC950, SREBP-1c
format	article
author	Liu B Mao X Huang D Li F Dong N
author_facet	Liu B Mao X Huang D Li F Dong N
author_sort	Liu B
title	Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
title_short	Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
title_full	Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
title_fullStr	Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
title_full_unstemmed	Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
title_sort	novel role of nlrp3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/5b37ca73dbc0437a8b6f58ee6a1b66fe
work_keys_str_mv	AT liub novelroleofnlrp3inflammasomeinregulationoflipogenesisinfastinginducedhepaticsteatosis AT maox novelroleofnlrp3inflammasomeinregulationoflipogenesisinfastinginducedhepaticsteatosis AT huangd novelroleofnlrp3inflammasomeinregulationoflipogenesisinfastinginducedhepaticsteatosis AT lif novelroleofnlrp3inflammasomeinregulationoflipogenesisinfastinginducedhepaticsteatosis AT dongn novelroleofnlrp3inflammasomeinregulationoflipogenesisinfastinginducedhepaticsteatosis
_version_	1718397882964377600

Novel role of NLRP3-inflammasome in regulation of lipogenesis in fasting-induced hepatic steatosis

Ejemplares similares