Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice

Abstract Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic un...

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Autores principales:	Lan N. Tu, Megan R. Showalter, Tomas Cajka, Sili Fan, Viju V. Pillai, Oliver Fiehn, Vimal Selvaraj
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/273c2e5360d44f8d90ee63f1a2c4e581
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spelling	oai:doaj.org-article:273c2e5360d44f8d90ee63f1a2c4e5812021-12-02T16:06:34ZMetabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice10.1038/s41598-017-05040-62045-2322https://doaj.org/article/273c2e5360d44f8d90ee63f1a2c4e5812017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05040-6https://doaj.org/toc/2045-2322Abstract Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients.Lan N. TuMegan R. ShowalterTomas CajkaSili FanViju V. PillaiOliver FiehnVimal SelvarajNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lan N. Tu Megan R. Showalter Tomas Cajka Sili Fan Viju V. Pillai Oliver Fiehn Vimal Selvaraj Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
description	Abstract Nonalcoholic fatty liver disease (NAFLD) in non-obese patients remains a clinical condition with unclear etiology and pathogenesis. Using a metabolomics approach in a mouse model that recapitulates almost all the characteristic features of non-obese NAFLD, we aimed to advance mechanistic understanding of this disorder. Mice fed high fat, high cholesterol, cholate (HFHCC) diet for three weeks consistently developed hepatic pathology similar to NAFLD and nonalcoholic steatohepatitis (NASH) without changes to body weight or fat pad weights. Gas- and liquid chromatography/mass spectrometry-based profiling of lipidomic and primary metabolism changes in the liver and plasma revealed that systemic mechanisms leading to steatosis and hepatitis in this non-obese NAFLD model were driven by a combination of effects directed by elevated free cholesterol, cholesterol esters and cholic acid, and associated changes to metabolism of sphingomyelins and phosphatidylcholines. These results demonstrate that mechanisms underlying cholesterol-induced non-obese NAFLD are distinct from NAFLD occurring as a consequence of metabolic syndrome. In addition, this investigation provides one of the first metabolite reference profiles for interpreting effects of dietary and hepatic cholesterol in human non-obese NAFLD/NASH patients.
format	article
author	Lan N. Tu Megan R. Showalter Tomas Cajka Sili Fan Viju V. Pillai Oliver Fiehn Vimal Selvaraj
author_facet	Lan N. Tu Megan R. Showalter Tomas Cajka Sili Fan Viju V. Pillai Oliver Fiehn Vimal Selvaraj
author_sort	Lan N. Tu
title	Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
title_short	Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
title_full	Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
title_fullStr	Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
title_full_unstemmed	Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
title_sort	metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/273c2e5360d44f8d90ee63f1a2c4e581
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Metabolomic characteristics of cholesterol-induced non-obese nonalcoholic fatty liver disease in mice

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