Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes

Leptin, a hormone that is predominantly produced by adipose tissue, is closely associated with various liver diseases. However, there is a lack of understanding as to whether leptin directly induces cytotoxic effects in hepatocytes as well as the mechanisms that are involved. Inflammasomes, which ar...

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Autores principales:	Ananda Baral, Pil-Hoon Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	autophagy ER stress hepatocyte inflammasomes leptin Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/2d272c674d1046009f693b32b28fb8a8
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spelling	oai:doaj.org-article:2d272c674d1046009f693b32b28fb8a82021-11-25T17:58:05ZLeptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes10.3390/ijms2222125891422-00671661-6596https://doaj.org/article/2d272c674d1046009f693b32b28fb8a82021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12589https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Leptin, a hormone that is predominantly produced by adipose tissue, is closely associated with various liver diseases. However, there is a lack of understanding as to whether leptin directly induces cytotoxic effects in hepatocytes as well as the mechanisms that are involved. Inflammasomes, which are critical components in the innate immune system, have been recently shown to modulate cell death. In this study, we examined the effect of leptin on the viability of rat hepatocytes and the underlying mechanisms, with a particular focus on the role of inflammasomes activation. Leptin treatment induced cytotoxicity in rat hepatocytes, as determined by decreased cell viability, increased caspase-3 activity, and the enhanced release of lactate dehydrogenase. NLRP3 inflammasomes were activated by leptin both in vitro and in vivo, as determined by the maturation of interleukin-1β and caspase-1, and the increased expression of inflammasome components, including NLRP3 and ASC. Mechanistically, leptin-induced inflammasome activation is mediated via the axis of ROS production, ER stress, and autophagy. Notably, the inhibition of inflammasomes by treatment with the NLRP3 inhibitor or the IL-1 receptor antagonist protected the hepatocytes from leptin-induced cell death. Together, these results indicate that leptin exerts cytotoxic effects in hepatocytes, at least in part, via the activation of NLRP3 inflammasomes.Ananda BaralPil-Hoon ParkMDPI AGarticleautophagyER stresshepatocyteinflammasomesleptinBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12589, p 12589 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	autophagy ER stress hepatocyte inflammasomes leptin Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	autophagy ER stress hepatocyte inflammasomes leptin Biology (General) QH301-705.5 Chemistry QD1-999 Ananda Baral Pil-Hoon Park Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
description	Leptin, a hormone that is predominantly produced by adipose tissue, is closely associated with various liver diseases. However, there is a lack of understanding as to whether leptin directly induces cytotoxic effects in hepatocytes as well as the mechanisms that are involved. Inflammasomes, which are critical components in the innate immune system, have been recently shown to modulate cell death. In this study, we examined the effect of leptin on the viability of rat hepatocytes and the underlying mechanisms, with a particular focus on the role of inflammasomes activation. Leptin treatment induced cytotoxicity in rat hepatocytes, as determined by decreased cell viability, increased caspase-3 activity, and the enhanced release of lactate dehydrogenase. NLRP3 inflammasomes were activated by leptin both in vitro and in vivo, as determined by the maturation of interleukin-1β and caspase-1, and the increased expression of inflammasome components, including NLRP3 and ASC. Mechanistically, leptin-induced inflammasome activation is mediated via the axis of ROS production, ER stress, and autophagy. Notably, the inhibition of inflammasomes by treatment with the NLRP3 inhibitor or the IL-1 receptor antagonist protected the hepatocytes from leptin-induced cell death. Together, these results indicate that leptin exerts cytotoxic effects in hepatocytes, at least in part, via the activation of NLRP3 inflammasomes.
format	article
author	Ananda Baral Pil-Hoon Park
author_facet	Ananda Baral Pil-Hoon Park
author_sort	Ananda Baral
title	Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title_short	Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title_full	Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title_fullStr	Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title_full_unstemmed	Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title_sort	leptin induces apoptotic and pyroptotic cell death via nlrp3 inflammasome activation in rat hepatocytes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2d272c674d1046009f693b32b28fb8a8
work_keys_str_mv	AT anandabaral leptininducesapoptoticandpyroptoticcelldeathvianlrp3inflammasomeactivationinrathepatocytes AT pilhoonpark leptininducesapoptoticandpyroptoticcelldeathvianlrp3inflammasomeactivationinrathepatocytes
_version_	1718411791802826752

Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes

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