Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway
Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Buildin...
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Nature Portfolio
2024-03-01
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Online Access: | https://doi.org/10.1038/s41598-024-56970-x |
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author | Wenying Zhang Fuju Wu |
author_facet | Wenying Zhang Fuju Wu |
author_sort | Wenying Zhang |
collection | DOAJ |
description | Abstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS. |
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language | English |
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spelling | doaj.art-75fc50d5d5244a839f3f0f9a3f5d5c3e2024-03-17T12:21:45ZengNature PortfolioScientific Reports2045-23222024-03-0114111310.1038/s41598-024-56970-xLinoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathwayWenying Zhang0Fuju Wu1Department of Obstetrics and Gynecology, The Second Hospital of Jilin UniversityDepartment of Obstetrics and Gynecology, The Second Hospital of Jilin UniversityAbstract Polycystic ovary syndrome (PCOS) is a complex reproductive endocrinological disorder influenced by a combination of genetic and environmental factors. Linoleic acid (LA) is a widely consumed ω-6 polyunsaturated fatty acid, accounting for approximately 80% of daily fatty acid intake. Building upon the prior investigations of our team, which established a connection between LA levels in the follicular fluid and PCOS, this study deeply examined the specific impact of LA using a granulosa cell line. Our findings revealed that LA exerts its influence on granulosa cells (GCs) by binding to the estrogen receptor (ER). Activated ER triggers the transcription of the FOXO1 gene. Reactive oxygen species (ROS)-related oxidative stress (OS) and inflammation occur downstream of LA-induced FOXO1 activation. Increased OS and inflammation ultimately culminate in GC apoptosis. In summary, LA modulates the apoptosis and inflammation phenotypes of GCs through the ER-FOXO1-ROS-NF-κB pathway. Our study provides additional experimental evidence to comprehend the pathophysiology of PCOS and provides novel insights into the dietary management of individuals with PCOS.https://doi.org/10.1038/s41598-024-56970-xLinoleic acidGranulosa cellDietary fatty acidsPolycystic ovary syndromeApoptosisEstrogen receptor |
spellingShingle | Wenying Zhang Fuju Wu Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway Scientific Reports Linoleic acid Granulosa cell Dietary fatty acids Polycystic ovary syndrome Apoptosis Estrogen receptor |
title | Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway |
title_full | Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway |
title_fullStr | Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway |
title_full_unstemmed | Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway |
title_short | Linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the ER-FOXO1-ROS-NFκB pathway |
title_sort | linoleic acid induces human ovarian granulosa cell inflammation and apoptosis through the er foxo1 ros nfκb pathway |
topic | Linoleic acid Granulosa cell Dietary fatty acids Polycystic ovary syndrome Apoptosis Estrogen receptor |
url | https://doi.org/10.1038/s41598-024-56970-x |
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