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Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice

Maternal obesity is one of the major risk factors for pregnancy complications and is associated with low-grade chronic systemic inflammation due to higher levels of pro-inflammatory cytokines such as interleukin (IL)-1β. Pregnant women with obesity have abnormal lipid profiles, characterized by high...

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Autores principales: SANO, Michiya, SHIMAZAKI, Sayaka, KANEKO, Yasuaki, KARASAWA, Tadayoshi, TAKAHASHI, Masafumi, OHKUCHI, Akihide, TAKAHASHI, Hironori, KUROSAWA, Akira, TORII, Yasushi, IWATA, Hisataka, KUWAYAMA, Takehito, SHIRASUNA, Koumei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Society for Reproduction and Development 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297640/
https://www.ncbi.nlm.nih.gov/pubmed/32101829
http://dx.doi.org/10.1262/jrd.2020-007
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author SANO, Michiya
SHIMAZAKI, Sayaka
KANEKO, Yasuaki
KARASAWA, Tadayoshi
TAKAHASHI, Masafumi
OHKUCHI, Akihide
TAKAHASHI, Hironori
KUROSAWA, Akira
TORII, Yasushi
IWATA, Hisataka
KUWAYAMA, Takehito
SHIRASUNA, Koumei
author_facet SANO, Michiya
SHIMAZAKI, Sayaka
KANEKO, Yasuaki
KARASAWA, Tadayoshi
TAKAHASHI, Masafumi
OHKUCHI, Akihide
TAKAHASHI, Hironori
KUROSAWA, Akira
TORII, Yasushi
IWATA, Hisataka
KUWAYAMA, Takehito
SHIRASUNA, Koumei
author_sort SANO, Michiya
collection PubMed
description Maternal obesity is one of the major risk factors for pregnancy complications and is associated with low-grade chronic systemic inflammation due to higher levels of pro-inflammatory cytokines such as interleukin (IL)-1β. Pregnant women with obesity have abnormal lipid profiles, characterized by higher levels of free fatty acids, especially palmitic acid (PA). Previously, we reported that PA stimulated IL-1β secretion via activation of NLRP3 inflammasome in human placental cells. These observations led us to hypothesize that higher levels of PA induce NLRP3 inflammasome activation and placental inflammation, resulting in pregnancy complications. However, the effects of PA on NLRP3 inflammasome during pregnancy in vivo remain unclear. Therefore, PA solutions were administered intravenously into pregnant mice on day 12 of gestation. Maternal body weight was significantly decreased and absorption rates were significantly higher in PA-injected mice. The administration of PA significantly increased IL-1β protein and the mRNA expression of NLRP3 inflammasome components (NLRP3,ASC, and caspase-1) within the placenta. In murine placental cell culture, PA significantly stimulated IL-1β secretion, and this secretion was suppressed by a specific NLRP3 inhibitor (MCC950). Simultaneously, the number of macrophages/monocytes and neutrophils, together with the mRNA expression of these chemokines increased significantly in the placentas of PA-treated mice. Treatment with PA induced ASC assembling and IL-1β secretion in macrophages, and this PA-induced IL-1β secretion was significantly suppressed in NLRP3-knockdown macrophages. These results indicate that transient higher levels of PA exposure in pregnant mice activates NLRP3 inflammasome and induces placental inflammation, resulting in the incidence of absorption.
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spelling pubmed-72976402020-06-22 Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice SANO, Michiya SHIMAZAKI, Sayaka KANEKO, Yasuaki KARASAWA, Tadayoshi TAKAHASHI, Masafumi OHKUCHI, Akihide TAKAHASHI, Hironori KUROSAWA, Akira TORII, Yasushi IWATA, Hisataka KUWAYAMA, Takehito SHIRASUNA, Koumei J Reprod Dev Original Article Maternal obesity is one of the major risk factors for pregnancy complications and is associated with low-grade chronic systemic inflammation due to higher levels of pro-inflammatory cytokines such as interleukin (IL)-1β. Pregnant women with obesity have abnormal lipid profiles, characterized by higher levels of free fatty acids, especially palmitic acid (PA). Previously, we reported that PA stimulated IL-1β secretion via activation of NLRP3 inflammasome in human placental cells. These observations led us to hypothesize that higher levels of PA induce NLRP3 inflammasome activation and placental inflammation, resulting in pregnancy complications. However, the effects of PA on NLRP3 inflammasome during pregnancy in vivo remain unclear. Therefore, PA solutions were administered intravenously into pregnant mice on day 12 of gestation. Maternal body weight was significantly decreased and absorption rates were significantly higher in PA-injected mice. The administration of PA significantly increased IL-1β protein and the mRNA expression of NLRP3 inflammasome components (NLRP3,ASC, and caspase-1) within the placenta. In murine placental cell culture, PA significantly stimulated IL-1β secretion, and this secretion was suppressed by a specific NLRP3 inhibitor (MCC950). Simultaneously, the number of macrophages/monocytes and neutrophils, together with the mRNA expression of these chemokines increased significantly in the placentas of PA-treated mice. Treatment with PA induced ASC assembling and IL-1β secretion in macrophages, and this PA-induced IL-1β secretion was significantly suppressed in NLRP3-knockdown macrophages. These results indicate that transient higher levels of PA exposure in pregnant mice activates NLRP3 inflammasome and induces placental inflammation, resulting in the incidence of absorption. The Society for Reproduction and Development 2020-02-27 2020-06 /pmc/articles/PMC7297640/ /pubmed/32101829 http://dx.doi.org/10.1262/jrd.2020-007 Text en ©2020 Society for Reproduction and Development This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)
spellingShingle Original Article
SANO, Michiya
SHIMAZAKI, Sayaka
KANEKO, Yasuaki
KARASAWA, Tadayoshi
TAKAHASHI, Masafumi
OHKUCHI, Akihide
TAKAHASHI, Hironori
KUROSAWA, Akira
TORII, Yasushi
IWATA, Hisataka
KUWAYAMA, Takehito
SHIRASUNA, Koumei
Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title_full Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title_fullStr Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title_full_unstemmed Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title_short Palmitic acid activates NLRP3 inflammasome and induces placental inflammation during pregnancy in mice
title_sort palmitic acid activates nlrp3 inflammasome and induces placental inflammation during pregnancy in mice
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297640/
https://www.ncbi.nlm.nih.gov/pubmed/32101829
http://dx.doi.org/10.1262/jrd.2020-007
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