Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis

Abstract Non-alcoholic fatty liver disease closely contributes to the development of obesity and insulin resistance. Even though pioglitazone has been reported to effectively lessen hepatic steatosis in human studies, its molecular mechanism remains unclear. This study is designed to investigate the...

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Autores principales:	Pi-Jung Hsiao, Hsin-Ying Clair Chiou, He-Jiun Jiang, Mei-Yueh Lee, Tusty-Jiuan Hsieh, Kung-Kai Kuo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0da5b63457f741fca1c8e27f395d5c0e
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spelling	oai:doaj.org-article:0da5b63457f741fca1c8e27f395d5c0e2021-12-02T15:05:25ZPioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis10.1038/s41598-017-09702-32045-2322https://doaj.org/article/0da5b63457f741fca1c8e27f395d5c0e2017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09702-3https://doaj.org/toc/2045-2322Abstract Non-alcoholic fatty liver disease closely contributes to the development of obesity and insulin resistance. Even though pioglitazone has been reported to effectively lessen hepatic steatosis in human studies, its molecular mechanism remains unclear. This study is designed to investigate the regulation of cytosolic lipolysis, β-oxidation and autophagy by pioglitazone in a mice model of high fat diet (HFD) and cell model incubated with palmitic acid. Our results revealed hepatic steatosis was apparently induced by HFD and it was significantly reversed by pioglitazone. The serum insulin and hepatic triglyceride content was significantly decreased by co-administered pioglitazone with HFD. Hepatic expression of cytosolic-lipolysis related proteins (ATGL, HSL), β-oxidation (CPT-1A) and autophagy-related proteins (ATG7, LC3, LAL) was significantly enhanced by pioglitazone. Knockdown PPARα/PPARγ in AML12 cells significantly and proportionally reduced the expressions of ATGL, CPT-1A and LC3II, which was induced by pioglitazone. Furthermore, facilitation of the autophagic flux by pioglitazone was obviously blocked by lysosomal inhibitor, leupeptin, to demonstrate accumulation of the LC3II and intracellular lipid in AML12 cells. Our results demonstrated that pioglitazone attenuating the hepatic steatosis may be mediated by enhancing cytosolic lipolysis, β-oxidation and autophagy in a PPARα and PPARγ dependent manner.Pi-Jung HsiaoHsin-Ying Clair ChiouHe-Jiun JiangMei-Yueh LeeTusty-Jiuan HsiehKung-Kai KuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pi-Jung Hsiao Hsin-Ying Clair Chiou He-Jiun Jiang Mei-Yueh Lee Tusty-Jiuan Hsieh Kung-Kai Kuo Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
description	Abstract Non-alcoholic fatty liver disease closely contributes to the development of obesity and insulin resistance. Even though pioglitazone has been reported to effectively lessen hepatic steatosis in human studies, its molecular mechanism remains unclear. This study is designed to investigate the regulation of cytosolic lipolysis, β-oxidation and autophagy by pioglitazone in a mice model of high fat diet (HFD) and cell model incubated with palmitic acid. Our results revealed hepatic steatosis was apparently induced by HFD and it was significantly reversed by pioglitazone. The serum insulin and hepatic triglyceride content was significantly decreased by co-administered pioglitazone with HFD. Hepatic expression of cytosolic-lipolysis related proteins (ATGL, HSL), β-oxidation (CPT-1A) and autophagy-related proteins (ATG7, LC3, LAL) was significantly enhanced by pioglitazone. Knockdown PPARα/PPARγ in AML12 cells significantly and proportionally reduced the expressions of ATGL, CPT-1A and LC3II, which was induced by pioglitazone. Furthermore, facilitation of the autophagic flux by pioglitazone was obviously blocked by lysosomal inhibitor, leupeptin, to demonstrate accumulation of the LC3II and intracellular lipid in AML12 cells. Our results demonstrated that pioglitazone attenuating the hepatic steatosis may be mediated by enhancing cytosolic lipolysis, β-oxidation and autophagy in a PPARα and PPARγ dependent manner.
format	article
author	Pi-Jung Hsiao Hsin-Ying Clair Chiou He-Jiun Jiang Mei-Yueh Lee Tusty-Jiuan Hsieh Kung-Kai Kuo
author_facet	Pi-Jung Hsiao Hsin-Ying Clair Chiou He-Jiun Jiang Mei-Yueh Lee Tusty-Jiuan Hsieh Kung-Kai Kuo
author_sort	Pi-Jung Hsiao
title	Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
title_short	Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
title_full	Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
title_fullStr	Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
title_full_unstemmed	Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis
title_sort	pioglitazone enhances cytosolic lipolysis, β-oxidation and autophagy to ameliorate hepatic steatosis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0da5b63457f741fca1c8e27f395d5c0e
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_version_	1718388812755763200

Pioglitazone Enhances Cytosolic Lipolysis, β-oxidation and Autophagy to Ameliorate Hepatic Steatosis

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