Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy

Abstract Previous studies have demonstrated that saturated fatty acids (SFAs) are more lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and promoting non-alcoholic steatohepatitis (NASH). However, there have been few studies have investigated the effects of carbon chain...

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Autores principales:	Mu-En Wang, Brijesh K. Singh, Meng-Chieh Hsu, Chien Huang, Paul M. Yen, Leang-Shin Wu, De-Shien Jong, Chih-Hsien Chiu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c6edea5ff3c74a4da44c0abc0815201a
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spelling	oai:doaj.org-article:c6edea5ff3c74a4da44c0abc0815201a2021-12-02T15:06:23ZIncreasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy10.1038/s41598-017-14376-y2045-2322https://doaj.org/article/c6edea5ff3c74a4da44c0abc0815201a2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14376-yhttps://doaj.org/toc/2045-2322Abstract Previous studies have demonstrated that saturated fatty acids (SFAs) are more lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and promoting non-alcoholic steatohepatitis (NASH). However, there have been few studies have investigated the effects of carbon chain length on SFA-induced autophagy impairment and lipotoxicity. To investigate whether SFAs with shorter carbon chain lengths have differential effects on hepatic autophagy and NASH development, we partially replaced lard with coconut oil to elevate the ratio of medium-chain fatty acids (MCFAs) to long-chain fatty acids (LCFAs) in a mouse high-fat diet (HFD) and fed mice for 16 weeks. In addition, we treated HepG2 cells with different combinations of fatty acids to study the mechanisms of MCFAs-mediated hepatic protections. Our results showed that increasing dietary MCFA/LCFA ratio mitigated HFD-induced Type 2 diabetes and NASH in mice. Importantly, we demonstrated that increased MCFA ratio exerted its protective effects by restoring Rubicon-suppressed autophagy. Our study suggests that the relative amount of LCFAs and MCFAs in the diet, in addition to the amount of SFAs, can significantly contribute to autophagy impairment and hepatic lipotoxicity. Collectively, we propose that increasing dietary MCFAs could be an alternative therapeutic and prevention strategy for Type 2 diabetes and NASH.Mu-En WangBrijesh K. SinghMeng-Chieh HsuChien HuangPaul M. YenLeang-Shin WuDe-Shien JongChih-Hsien ChiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mu-En Wang Brijesh K. Singh Meng-Chieh Hsu Chien Huang Paul M. Yen Leang-Shin Wu De-Shien Jong Chih-Hsien Chiu Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
description	Abstract Previous studies have demonstrated that saturated fatty acids (SFAs) are more lipotoxic than unsaturated fatty acids (UFAs) in inhibiting hepatic autophagy and promoting non-alcoholic steatohepatitis (NASH). However, there have been few studies have investigated the effects of carbon chain length on SFA-induced autophagy impairment and lipotoxicity. To investigate whether SFAs with shorter carbon chain lengths have differential effects on hepatic autophagy and NASH development, we partially replaced lard with coconut oil to elevate the ratio of medium-chain fatty acids (MCFAs) to long-chain fatty acids (LCFAs) in a mouse high-fat diet (HFD) and fed mice for 16 weeks. In addition, we treated HepG2 cells with different combinations of fatty acids to study the mechanisms of MCFAs-mediated hepatic protections. Our results showed that increasing dietary MCFA/LCFA ratio mitigated HFD-induced Type 2 diabetes and NASH in mice. Importantly, we demonstrated that increased MCFA ratio exerted its protective effects by restoring Rubicon-suppressed autophagy. Our study suggests that the relative amount of LCFAs and MCFAs in the diet, in addition to the amount of SFAs, can significantly contribute to autophagy impairment and hepatic lipotoxicity. Collectively, we propose that increasing dietary MCFAs could be an alternative therapeutic and prevention strategy for Type 2 diabetes and NASH.
format	article
author	Mu-En Wang Brijesh K. Singh Meng-Chieh Hsu Chien Huang Paul M. Yen Leang-Shin Wu De-Shien Jong Chih-Hsien Chiu
author_facet	Mu-En Wang Brijesh K. Singh Meng-Chieh Hsu Chien Huang Paul M. Yen Leang-Shin Wu De-Shien Jong Chih-Hsien Chiu
author_sort	Mu-En Wang
title	Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
title_short	Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
title_full	Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
title_fullStr	Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
title_full_unstemmed	Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy
title_sort	increasing dietary medium-chain fatty acid ratio mitigates high-fat diet-induced non-alcoholic steatohepatitis by regulating autophagy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c6edea5ff3c74a4da44c0abc0815201a
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Increasing Dietary Medium-Chain Fatty Acid Ratio Mitigates High-fat Diet-Induced Non-Alcoholic Steatohepatitis by Regulating Autophagy

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