Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis

Abstract Non-alcoholic fatty liver disease (NAFLD) results from triglyceride accumulation within the liver and some of them advances to non-alcoholic steatohepatitis (NASH). It is important to note that in NAFLD development, hepatic de novo lipogenesis (DNL) derives from excess carbohydrates and fat...

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Autores principales:	Sang R. Lee, Sun Woo Kwon, Pelin Kaya, Young Ho Lee, Jong Geol Lee, Globinna Kim, Geun-Shik Lee, In-Jeoung Baek, Eui-Ju Hong
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Progesterone Receptor Membrane Component 1 (PGRMC1) Non-alcoholic Steatohepatitis (NASH) Non-alcoholic Fatty Liver Disease (NAFLD) NAFLD Development Excess Energy Conditions Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0178d83a786046cfa39dfbfd36639d30
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spelling	oai:doaj.org-article:0178d83a786046cfa39dfbfd36639d302021-12-02T11:41:23ZLoss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis10.1038/s41598-018-34148-62045-2322https://doaj.org/article/0178d83a786046cfa39dfbfd36639d302018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-34148-6https://doaj.org/toc/2045-2322Abstract Non-alcoholic fatty liver disease (NAFLD) results from triglyceride accumulation within the liver and some of them advances to non-alcoholic steatohepatitis (NASH). It is important to note that in NAFLD development, hepatic de novo lipogenesis (DNL) derives from excess carbohydrates and fats under a condition of excess energy through β-oxidation. As a main regulator for DNL, sterol regulatory element-binding protein 1 (Srebp-1) forms complex with progesterone receptor membrane component 1 (Pgrmc1). To investigate whether Pgrmc1 may have a notable effect on DNL via SREBP-1 activation, we generated Pgrmc1 knockout (KO) mice and fed a high fat diet for one month. High-fat-fed Pgrmc1 KO mice showed a substantial increase in levels of hepatic TG accumulation, and they were predisposed to NAFLD when compared to WT mice. Loss of Pgrmc1 increased mature SREBP-1 protein level, suggesting that induction of hepatic steatosis in Pgrmc1 KO mice might be triggered by de novo lipogenesis. Moreover, Pgrmc1 KO mice were also more vulnerable to early stage of NASH, showing high levels of alanine aminotransferase, obesity-linked pro-inflammatory cytokines, and fibrosis markers. This is interesting because Pgrmc1 involves with the first step in regulating the hepatic de novo lipogenesis under an excess energy condition.Sang R. LeeSun Woo KwonPelin KayaYoung Ho LeeJong Geol LeeGlobinna KimGeun-Shik LeeIn-Jeoung BaekEui-Ju HongNature PortfolioarticleProgesterone Receptor Membrane Component 1 (PGRMC1)Non-alcoholic Steatohepatitis (NASH)Non-alcoholic Fatty Liver Disease (NAFLD)NAFLD DevelopmentExcess Energy ConditionsMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Progesterone Receptor Membrane Component 1 (PGRMC1) Non-alcoholic Steatohepatitis (NASH) Non-alcoholic Fatty Liver Disease (NAFLD) NAFLD Development Excess Energy Conditions Medicine R Science Q
spellingShingle	Progesterone Receptor Membrane Component 1 (PGRMC1) Non-alcoholic Steatohepatitis (NASH) Non-alcoholic Fatty Liver Disease (NAFLD) NAFLD Development Excess Energy Conditions Medicine R Science Q Sang R. Lee Sun Woo Kwon Pelin Kaya Young Ho Lee Jong Geol Lee Globinna Kim Geun-Shik Lee In-Jeoung Baek Eui-Ju Hong Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
description	Abstract Non-alcoholic fatty liver disease (NAFLD) results from triglyceride accumulation within the liver and some of them advances to non-alcoholic steatohepatitis (NASH). It is important to note that in NAFLD development, hepatic de novo lipogenesis (DNL) derives from excess carbohydrates and fats under a condition of excess energy through β-oxidation. As a main regulator for DNL, sterol regulatory element-binding protein 1 (Srebp-1) forms complex with progesterone receptor membrane component 1 (Pgrmc1). To investigate whether Pgrmc1 may have a notable effect on DNL via SREBP-1 activation, we generated Pgrmc1 knockout (KO) mice and fed a high fat diet for one month. High-fat-fed Pgrmc1 KO mice showed a substantial increase in levels of hepatic TG accumulation, and they were predisposed to NAFLD when compared to WT mice. Loss of Pgrmc1 increased mature SREBP-1 protein level, suggesting that induction of hepatic steatosis in Pgrmc1 KO mice might be triggered by de novo lipogenesis. Moreover, Pgrmc1 KO mice were also more vulnerable to early stage of NASH, showing high levels of alanine aminotransferase, obesity-linked pro-inflammatory cytokines, and fibrosis markers. This is interesting because Pgrmc1 involves with the first step in regulating the hepatic de novo lipogenesis under an excess energy condition.
format	article
author	Sang R. Lee Sun Woo Kwon Pelin Kaya Young Ho Lee Jong Geol Lee Globinna Kim Geun-Shik Lee In-Jeoung Baek Eui-Ju Hong
author_facet	Sang R. Lee Sun Woo Kwon Pelin Kaya Young Ho Lee Jong Geol Lee Globinna Kim Geun-Shik Lee In-Jeoung Baek Eui-Ju Hong
author_sort	Sang R. Lee
title	Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
title_short	Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
title_full	Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
title_fullStr	Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
title_full_unstemmed	Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
title_sort	loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0178d83a786046cfa39dfbfd36639d30
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Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis

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