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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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Detalles Bibliográficos
Autores principales: Baral, Ananda, Park, Pil-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622994/
https://www.ncbi.nlm.nih.gov/pubmed/34830465
http://dx.doi.org/10.3390/ijms222212589
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author Baral, Ananda
Park, Pil-Hoon
author_facet Baral, Ananda
Park, Pil-Hoon
author_sort Baral, Ananda
collection PubMed
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.
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spelling pubmed-86229942021-11-27 Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes Baral, Ananda Park, Pil-Hoon Int J Mol Sci Article 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. MDPI 2021-11-22 /pmc/articles/PMC8622994/ /pubmed/34830465 http://dx.doi.org/10.3390/ijms222212589 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Baral, Ananda
Park, Pil-Hoon
Leptin Induces Apoptotic and Pyroptotic Cell Death via NLRP3 Inflammasome Activation in Rat Hepatocytes
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8622994/
https://www.ncbi.nlm.nih.gov/pubmed/34830465
http://dx.doi.org/10.3390/ijms222212589
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