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High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes, and dyslipidemia. The purpose of this study was to identify novel proteins and pathways that contribute to the pathogenesis and complications of NAFLD. C57BL/6J male mice were fed a 60% (HFD) or...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074682/ https://www.ncbi.nlm.nih.gov/pubmed/33907358 http://dx.doi.org/10.4172/jpb.1000214 |
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author | Luo, Moulun Mengos, April E. Stubblefield, Tianna M. Mandarino, Lawrence J. |
author_facet | Luo, Moulun Mengos, April E. Stubblefield, Tianna M. Mandarino, Lawrence J. |
author_sort | Luo, Moulun |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes, and dyslipidemia. The purpose of this study was to identify novel proteins and pathways that contribute to the pathogenesis and complications of NAFLD. C57BL/6J male mice were fed a 60% (HFD) or 10% (LFD) high or low fat diet. HFD induced obesity, hepatic steatosis and insulin resistance (euglycemic clamps, glucose infusion rate: LFD 50.5 ± 6.4 vs. HFD 14.2 ± 9.5 μg/ (g·min); n = 12). Liver proteins were analyzed by mass spectrometry-based proteomics analysis. Numerous hepatic proteins were altered in abundance after 60% HFD feeding. Nine down-regulated and nine up-regulated proteins were selected from this list for detailed analysis based on the criteria of 1.5-fold difference, consistency across replicates, and having at least 2 spectra assigned. Proteins that decreased in abundance were acyl-coA desaturase-I (SCD-1), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), pyruvate kinase isozymes R/L (PKLR), NADP-dependent malic enzyme (ME-1), ATP-citrate synthase (ACL), ketohexokinase (KHK), long-chain-fatty acid-CoA ligase-5 (ACSL-5) and carbamoyl-phosphate synthase-I (CPS-1). Those that increased were KIAA0564, apolipoprotein A-I (apoA-1), ornithine aminotransferase (OAT), multidrug resistance protein 2 (MRP-2), liver carboxylesterase-I (CES-1), aminopeptidase N (APN), fatty aldehyde dehydrogenase (FALDH), major urinary protein 2 (MUP-2) and KIAA0664. KIAA0564 and KIAA0664 proteins are uncharacterized and are novel proteins associated with NAFLD. The decreased abundance of normally highly abundant proteins like FAS and CPS-1 was confirmed by Coomassie Blue staining after bands were identified by MS/MS, and immunoblot analysis confirmed the increased abundance of KIAA0664 after 60% HFD feeding. In conclusion, this study shows NAFLD is characterized by changes in abundance of proteins related to cell injury, inflammation, and lipid metabolism. Two novel and uncharacterized proteins, KIAA0564 and KIAA0664, may provide insight into the pathogenesis of NAFLD induced by lipid oversupply. |
format | Online Article Text |
id | pubmed-8074682 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-80746822021-04-26 High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice Luo, Moulun Mengos, April E. Stubblefield, Tianna M. Mandarino, Lawrence J. J Proteomics Bioinform Article Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes, and dyslipidemia. The purpose of this study was to identify novel proteins and pathways that contribute to the pathogenesis and complications of NAFLD. C57BL/6J male mice were fed a 60% (HFD) or 10% (LFD) high or low fat diet. HFD induced obesity, hepatic steatosis and insulin resistance (euglycemic clamps, glucose infusion rate: LFD 50.5 ± 6.4 vs. HFD 14.2 ± 9.5 μg/ (g·min); n = 12). Liver proteins were analyzed by mass spectrometry-based proteomics analysis. Numerous hepatic proteins were altered in abundance after 60% HFD feeding. Nine down-regulated and nine up-regulated proteins were selected from this list for detailed analysis based on the criteria of 1.5-fold difference, consistency across replicates, and having at least 2 spectra assigned. Proteins that decreased in abundance were acyl-coA desaturase-I (SCD-1), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), pyruvate kinase isozymes R/L (PKLR), NADP-dependent malic enzyme (ME-1), ATP-citrate synthase (ACL), ketohexokinase (KHK), long-chain-fatty acid-CoA ligase-5 (ACSL-5) and carbamoyl-phosphate synthase-I (CPS-1). Those that increased were KIAA0564, apolipoprotein A-I (apoA-1), ornithine aminotransferase (OAT), multidrug resistance protein 2 (MRP-2), liver carboxylesterase-I (CES-1), aminopeptidase N (APN), fatty aldehyde dehydrogenase (FALDH), major urinary protein 2 (MUP-2) and KIAA0664. KIAA0564 and KIAA0664 proteins are uncharacterized and are novel proteins associated with NAFLD. The decreased abundance of normally highly abundant proteins like FAS and CPS-1 was confirmed by Coomassie Blue staining after bands were identified by MS/MS, and immunoblot analysis confirmed the increased abundance of KIAA0664 after 60% HFD feeding. In conclusion, this study shows NAFLD is characterized by changes in abundance of proteins related to cell injury, inflammation, and lipid metabolism. Two novel and uncharacterized proteins, KIAA0564 and KIAA0664, may provide insight into the pathogenesis of NAFLD induced by lipid oversupply. 2012-02-29 2012 /pmc/articles/PMC8074682/ /pubmed/33907358 http://dx.doi.org/10.4172/jpb.1000214 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Luo, Moulun Mengos, April E. Stubblefield, Tianna M. Mandarino, Lawrence J. High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title_full | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title_fullStr | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title_full_unstemmed | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title_short | High Fat Diet-Induced Changes in Hepatic Protein Abundance in Mice |
title_sort | high fat diet-induced changes in hepatic protein abundance in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074682/ https://www.ncbi.nlm.nih.gov/pubmed/33907358 http://dx.doi.org/10.4172/jpb.1000214 |
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