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Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity

Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to...

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Autores principales: Shih, Lu-Min, Tang, Hsiang-Yu, Lynn, Ke-Shiuan, Huang, Cheng-Yu, Ho, Hung-Yao, Cheng, Mei-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278256/
https://www.ncbi.nlm.nih.gov/pubmed/30400243
http://dx.doi.org/10.3390/molecules23112862
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author Shih, Lu-Min
Tang, Hsiang-Yu
Lynn, Ke-Shiuan
Huang, Cheng-Yu
Ho, Hung-Yao
Cheng, Mei-Ling
author_facet Shih, Lu-Min
Tang, Hsiang-Yu
Lynn, Ke-Shiuan
Huang, Cheng-Yu
Ho, Hung-Yao
Cheng, Mei-Ling
author_sort Shih, Lu-Min
collection PubMed
description Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes. C16:0 induced inflammation and cell death, whereas C16:1 induced significant lipid droplet accumulation. Moreover, inhibition of de novo sphingolipid synthesis by myriocin (Myr) aggravated C16:0 induced lipoapoptosis. Lipid profiles are different in C16:0 and C16:1-treated cells. Stable isotope-labeled lipidomics elucidates the roles of specific fatty acids that affect lipid metabolism and cause lipotoxicity or lipid droplet formation. It indicates that not only saturation or monounsaturation of fatty acids plays a role in hepatic lipotoxicity but also Myr inhibition exasperates lipoapoptosis through ceramide in-direct pathway. Using the techniques presented in this study, we can potentially investigate the mechanism of lipid metabolism and the heterogeneous development of NAFLD.
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spelling pubmed-62782562018-12-13 Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity Shih, Lu-Min Tang, Hsiang-Yu Lynn, Ke-Shiuan Huang, Cheng-Yu Ho, Hung-Yao Cheng, Mei-Ling Molecules Article Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes. C16:0 induced inflammation and cell death, whereas C16:1 induced significant lipid droplet accumulation. Moreover, inhibition of de novo sphingolipid synthesis by myriocin (Myr) aggravated C16:0 induced lipoapoptosis. Lipid profiles are different in C16:0 and C16:1-treated cells. Stable isotope-labeled lipidomics elucidates the roles of specific fatty acids that affect lipid metabolism and cause lipotoxicity or lipid droplet formation. It indicates that not only saturation or monounsaturation of fatty acids plays a role in hepatic lipotoxicity but also Myr inhibition exasperates lipoapoptosis through ceramide in-direct pathway. Using the techniques presented in this study, we can potentially investigate the mechanism of lipid metabolism and the heterogeneous development of NAFLD. MDPI 2018-11-02 /pmc/articles/PMC6278256/ /pubmed/30400243 http://dx.doi.org/10.3390/molecules23112862 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shih, Lu-Min
Tang, Hsiang-Yu
Lynn, Ke-Shiuan
Huang, Cheng-Yu
Ho, Hung-Yao
Cheng, Mei-Ling
Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title_full Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title_fullStr Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title_full_unstemmed Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title_short Stable Isotope-Labeled Lipidomics to Unravel the Heterogeneous Development Lipotoxicity
title_sort stable isotope-labeled lipidomics to unravel the heterogeneous development lipotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6278256/
https://www.ncbi.nlm.nih.gov/pubmed/30400243
http://dx.doi.org/10.3390/molecules23112862
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