Cargando…
Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis
BACKGROUND AND AIM: Impaired fatty liver regeneration has already been reported in many genetic modification models. However, in diet-induced simple hepatic steatosis, which showed similar phenotype with clinical pathology, whether liver regeneration is impaired or not remains unclear. In this study...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Japan
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925298/ https://www.ncbi.nlm.nih.gov/pubmed/23512345 http://dx.doi.org/10.1007/s00535-013-0780-7 |
_version_ | 1782303842925281280 |
---|---|
author | Hamano, Mina Ezaki, Hisao Kiso, Shinichi Furuta, Kunimaro Egawa, Mayumi Kizu, Takashi Chatani, Norihiro Kamada, Yoshihiro Yoshida, Yuichi Takehara, Tetsuo |
author_facet | Hamano, Mina Ezaki, Hisao Kiso, Shinichi Furuta, Kunimaro Egawa, Mayumi Kizu, Takashi Chatani, Norihiro Kamada, Yoshihiro Yoshida, Yuichi Takehara, Tetsuo |
author_sort | Hamano, Mina |
collection | PubMed |
description | BACKGROUND AND AIM: Impaired fatty liver regeneration has already been reported in many genetic modification models. However, in diet-induced simple hepatic steatosis, which showed similar phenotype with clinical pathology, whether liver regeneration is impaired or not remains unclear. In this study, we evaluated liver regeneration in mice with diet-induced simple hepatic steatosis, and focused on excess lipid accumulation occurring during liver regeneration. METHODS: Mice were fed high fat diet (HFD) or control diet for 9–10 weeks. We analyzed intrahepatic lipid accumulation, DNA replication, and various signaling pathways including cell proliferation and ER stress during liver regeneration after partial hepatectomy. In addition, some of mice were pretreated with tauroursodeoxycholic acid (TUDCA), a chemical chaperone which alleviates ER stress, and then we estimated TUDCA effects on liver regeneration. RESULTS: The peak of hepatocyte BrdU incorporation, the expression of proliferation cell nuclear antigen (PCNA) protein, and the expressions of cell cycle-related genes were observed in delayed time in HFD mice. The expression of phosphorylated Erk1/2 was also delayed in HFD mice. The amounts of liver triglyceride were at least twofold higher in HFD mice at each time point. Intrahepatic palmitic acid was increased especially in HFD mice. ER stress induced during liver regeneration was significantly higher in HFD mice. In HFD mice, pretreatment with TUDCA reduced ER stress and resulted in improvement of delayed liver regeneration. CONCLUSION: In simple hepatic steatosis, lipid overloading occurring during liver regeneration might be caused ER stress and results in delayed hepatocyte DNA replication. |
format | Online Article Text |
id | pubmed-3925298 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Springer Japan |
record_format | MEDLINE/PubMed |
spelling | pubmed-39252982014-02-20 Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis Hamano, Mina Ezaki, Hisao Kiso, Shinichi Furuta, Kunimaro Egawa, Mayumi Kizu, Takashi Chatani, Norihiro Kamada, Yoshihiro Yoshida, Yuichi Takehara, Tetsuo J Gastroenterol Original Article—Liver, Pancreas, and Biliary Tract BACKGROUND AND AIM: Impaired fatty liver regeneration has already been reported in many genetic modification models. However, in diet-induced simple hepatic steatosis, which showed similar phenotype with clinical pathology, whether liver regeneration is impaired or not remains unclear. In this study, we evaluated liver regeneration in mice with diet-induced simple hepatic steatosis, and focused on excess lipid accumulation occurring during liver regeneration. METHODS: Mice were fed high fat diet (HFD) or control diet for 9–10 weeks. We analyzed intrahepatic lipid accumulation, DNA replication, and various signaling pathways including cell proliferation and ER stress during liver regeneration after partial hepatectomy. In addition, some of mice were pretreated with tauroursodeoxycholic acid (TUDCA), a chemical chaperone which alleviates ER stress, and then we estimated TUDCA effects on liver regeneration. RESULTS: The peak of hepatocyte BrdU incorporation, the expression of proliferation cell nuclear antigen (PCNA) protein, and the expressions of cell cycle-related genes were observed in delayed time in HFD mice. The expression of phosphorylated Erk1/2 was also delayed in HFD mice. The amounts of liver triglyceride were at least twofold higher in HFD mice at each time point. Intrahepatic palmitic acid was increased especially in HFD mice. ER stress induced during liver regeneration was significantly higher in HFD mice. In HFD mice, pretreatment with TUDCA reduced ER stress and resulted in improvement of delayed liver regeneration. CONCLUSION: In simple hepatic steatosis, lipid overloading occurring during liver regeneration might be caused ER stress and results in delayed hepatocyte DNA replication. Springer Japan 2013-03-20 2014 /pmc/articles/PMC3925298/ /pubmed/23512345 http://dx.doi.org/10.1007/s00535-013-0780-7 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.5/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Original Article—Liver, Pancreas, and Biliary Tract Hamano, Mina Ezaki, Hisao Kiso, Shinichi Furuta, Kunimaro Egawa, Mayumi Kizu, Takashi Chatani, Norihiro Kamada, Yoshihiro Yoshida, Yuichi Takehara, Tetsuo Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title | Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title_full | Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title_fullStr | Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title_full_unstemmed | Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title_short | Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis |
title_sort | lipid overloading during liver regeneration causes delayed hepatocyte dna replication by increasing er stress in mice with simple hepatic steatosis |
topic | Original Article—Liver, Pancreas, and Biliary Tract |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3925298/ https://www.ncbi.nlm.nih.gov/pubmed/23512345 http://dx.doi.org/10.1007/s00535-013-0780-7 |
work_keys_str_mv | AT hamanomina lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT ezakihisao lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT kisoshinichi lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT furutakunimaro lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT egawamayumi lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT kizutakashi lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT chataninorihiro lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT kamadayoshihiro lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT yoshidayuichi lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis AT takeharatetsuo lipidoverloadingduringliverregenerationcausesdelayedhepatocytednareplicationbyincreasingerstressinmicewithsimplehepaticsteatosis |