Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice

Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer...
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Autor*in:	Xiaoyang Zhu [verfasserIn] Qing Liu [verfasserIn] Andrew D. Patterson [verfasserIn] Arun K. Sharma [verfasserIn] Shantu G. Amin [verfasserIn] Samuel M. Cohen [verfasserIn] Frank J. Gonzalez [verfasserIn] Jeffrey M. Peters [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4 senescence

Übergeordnetes Werk:	In: Metabolites - MDPI AG, 2012, 13(2023), 8, p 936
Übergeordnetes Werk:	volume:13 ; year:2023 ; number:8, p 936

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/metabo13080936

Katalog-ID:	DOAJ093581459

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allfields	10.3390/metabo13080936 doi (DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d DE-627 ger DE-627 rakwb eng QR1-502 Xiaoyang Zhu verfasserin aut Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis. peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology Qing Liu verfasserin aut Andrew D. Patterson verfasserin aut Arun K. Sharma verfasserin aut Shantu G. Amin verfasserin aut Samuel M. Cohen verfasserin aut Frank J. Gonzalez verfasserin aut Jeffrey M. Peters verfasserin aut In Metabolites MDPI AG, 2012 13(2023), 8, p 936 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:13 year:2023 number:8, p 936 https://doi.org/10.3390/metabo13080936 kostenfrei https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d kostenfrei https://www.mdpi.com/2218-1989/13/8/936 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 8, p 936
spelling	10.3390/metabo13080936 doi (DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d DE-627 ger DE-627 rakwb eng QR1-502 Xiaoyang Zhu verfasserin aut Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis. peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology Qing Liu verfasserin aut Andrew D. Patterson verfasserin aut Arun K. Sharma verfasserin aut Shantu G. Amin verfasserin aut Samuel M. Cohen verfasserin aut Frank J. Gonzalez verfasserin aut Jeffrey M. Peters verfasserin aut In Metabolites MDPI AG, 2012 13(2023), 8, p 936 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:13 year:2023 number:8, p 936 https://doi.org/10.3390/metabo13080936 kostenfrei https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d kostenfrei https://www.mdpi.com/2218-1989/13/8/936 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 8, p 936
allfields_unstemmed	10.3390/metabo13080936 doi (DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d DE-627 ger DE-627 rakwb eng QR1-502 Xiaoyang Zhu verfasserin aut Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis. peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology Qing Liu verfasserin aut Andrew D. Patterson verfasserin aut Arun K. Sharma verfasserin aut Shantu G. Amin verfasserin aut Samuel M. Cohen verfasserin aut Frank J. Gonzalez verfasserin aut Jeffrey M. Peters verfasserin aut In Metabolites MDPI AG, 2012 13(2023), 8, p 936 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:13 year:2023 number:8, p 936 https://doi.org/10.3390/metabo13080936 kostenfrei https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d kostenfrei https://www.mdpi.com/2218-1989/13/8/936 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 8, p 936
allfieldsGer	10.3390/metabo13080936 doi (DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d DE-627 ger DE-627 rakwb eng QR1-502 Xiaoyang Zhu verfasserin aut Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis. peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology Qing Liu verfasserin aut Andrew D. Patterson verfasserin aut Arun K. Sharma verfasserin aut Shantu G. Amin verfasserin aut Samuel M. Cohen verfasserin aut Frank J. Gonzalez verfasserin aut Jeffrey M. Peters verfasserin aut In Metabolites MDPI AG, 2012 13(2023), 8, p 936 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:13 year:2023 number:8, p 936 https://doi.org/10.3390/metabo13080936 kostenfrei https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d kostenfrei https://www.mdpi.com/2218-1989/13/8/936 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 8, p 936
allfieldsSound	10.3390/metabo13080936 doi (DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d DE-627 ger DE-627 rakwb eng QR1-502 Xiaoyang Zhu verfasserin aut Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis. peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology Qing Liu verfasserin aut Andrew D. Patterson verfasserin aut Arun K. Sharma verfasserin aut Shantu G. Amin verfasserin aut Samuel M. Cohen verfasserin aut Frank J. Gonzalez verfasserin aut Jeffrey M. Peters verfasserin aut In Metabolites MDPI AG, 2012 13(2023), 8, p 936 (DE-627)718627164 (DE-600)2662251-8 22181989 nnns volume:13 year:2023 number:8, p 936 https://doi.org/10.3390/metabo13080936 kostenfrei https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d kostenfrei https://www.mdpi.com/2218-1989/13/8/936 kostenfrei https://doaj.org/toc/2218-1989 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2023 8, p 936
language	English
source	In Metabolites 13(2023), 8, p 936 volume:13 year:2023 number:8, p 936
sourceStr	In Metabolites 13(2023), 8, p 936 volume:13 year:2023 number:8, p 936
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence Microbiology
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container_title	Metabolites
authorswithroles_txt_mv	Xiaoyang Zhu @@aut@@ Qing Liu @@aut@@ Andrew D. Patterson @@aut@@ Arun K. Sharma @@aut@@ Shantu G. Amin @@aut@@ Samuel M. Cohen @@aut@@ Frank J. Gonzalez @@aut@@ Jeffrey M. Peters @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Xiaoyang Zhu
spellingShingle	Xiaoyang Zhu misc QR1-502 misc peroxisome proliferator-activated receptor-α (PPARα) misc hepatocarcinogenesis misc linoleic acid misc CD4<sup<+</sup< T cell misc senescence misc Microbiology Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice
authorStr	Xiaoyang Zhu
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topic_title	QR1-502 Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice peroxisome proliferator-activated receptor-α (PPARα) hepatocarcinogenesis linoleic acid CD4<sup<+</sup< T cell senescence
topic	misc QR1-502 misc peroxisome proliferator-activated receptor-α (PPARα) misc hepatocarcinogenesis misc linoleic acid misc CD4<sup<+</sup< T cell misc senescence misc Microbiology
topic_unstemmed	misc QR1-502 misc peroxisome proliferator-activated receptor-α (PPARα) misc hepatocarcinogenesis misc linoleic acid misc CD4<sup<+</sup< T cell misc senescence misc Microbiology
topic_browse	misc QR1-502 misc peroxisome proliferator-activated receptor-α (PPARα) misc hepatocarcinogenesis misc linoleic acid misc CD4<sup<+</sup< T cell misc senescence misc Microbiology
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title	Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice
ctrlnum	(DE-627)DOAJ093581459 (DE-599)DOAJ1049ad43d5d041adbdc3b51a8f7b2f5d
title_full	Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice
author_sort	Xiaoyang Zhu
journal	Metabolites
journalStr	Metabolites
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lang_code	eng
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publishDateSort	2023
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author_browse	Xiaoyang Zhu Qing Liu Andrew D. Patterson Arun K. Sharma Shantu G. Amin Samuel M. Cohen Frank J. Gonzalez Jeffrey M. Peters
container_volume	13
class	QR1-502
format_se	Elektronische Aufsätze
author-letter	Xiaoyang Zhu
doi_str_mv	10.3390/metabo13080936
author2-role	verfasserin
title_sort	accumulation of linoleic acid by altered peroxisome proliferator-activated receptor-α signaling is associated with age-dependent hepatocarcinogenesis in <i<ppara</i< transgenic mice
callnumber	QR1-502
title_auth	Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice
abstract	Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis.
abstractGer	Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis.
abstract_unstemmed	Long-term ligand activation of PPARα in mice causes hepatocarcinogenesis through a mechanism that requires functional PPARα. However, hepatocarcinogenesis is diminished in both <i<Ppara</i<-null and <i<PPARA</i<-humanized mice, yet both lines develop age-related liver cancer independently of treatment with a PPARα agonist. Since PPARα is a master regulator of liver lipid metabolism in the liver, lipidomic analyses were carried out in wild-type, <i<Ppara</i<-null, and <i<PPARA</i<-humanized mice treated with and without the potent agonist GW7647. The levels of hepatic linoleic acid in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice were markedly higher compared to wild-type controls, along with overall fatty liver. The number of liver CD4<sup<+</sup< T cells was also lower in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and was negatively correlated with the elevated linoleic acid. Moreover, more senescent hepatocytes and lower serum TNFα and IFNγ levels were observed in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice with age. These studies suggest a new role for PPARα in age-associated hepatocarcinogenesis due to altered lipid metabolism in <i<Ppara</i<-null and <i<PPARA</i<-humanized mice and the accumulation of linoleic acid as part of an overall fatty liver that is associated with loss of CD4<sup<+</sup< T cells in the liver in both transgenic models. Since fatty liver is a known causal risk factor for liver cancer, <i<Ppara</i<-null and <i<PPARA</i<-humanized mice are valuable models for examining the mechanisms of PPARα and age-dependent hepatocarcinogenesis.
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container_issue	8, p 936
title_short	Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice
url	https://doi.org/10.3390/metabo13080936 https://doaj.org/article/1049ad43d5d041adbdc3b51a8f7b2f5d https://www.mdpi.com/2218-1989/13/8/936 https://doaj.org/toc/2218-1989
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author2	Qing Liu Andrew D. Patterson Arun K. Sharma Shantu G. Amin Samuel M. Cohen Frank J. Gonzalez Jeffrey M. Peters
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doi_str	10.3390/metabo13080936
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up_date	2024-07-03T18:10:55.223Z
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Accumulation of Linoleic Acid by Altered Peroxisome Proliferator-Activated Receptor-α Signaling Is Associated with Age-Dependent Hepatocarcinogenesis in <i<Ppara</i< Transgenic Mice

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