Lipid overloading during liver regeneration causes delayed hepatocyte DNA replication by increasing ER stress in mice with simple hepatic steatosis

Autor: Yoshihiro Kamada, Mayumi Egawa, Kunimaro Furuta, Mina Hamano, Shinichi Kiso, Norihiro Chatani, Hisao Ezaki, Yuichi Yoshida, Takashi Kizu, Tetsuo Takehara
Rok vydání: 2013
Předmět:
Male
Cholagogues and Choleretics
Time Factors
medicine.medical_treatment
Gene Expression
Endoplasmic Reticulum
Mice
eIF-2 Kinase
Cyclin D1
Phosphorylation
Endoplasmic Reticulum Chaperone BiP
Heat-Shock Proteins
Fatty liver
Gastroenterology
Forkhead Transcription Factors
Organ Size
Liver regeneration
DNA-Binding Proteins
medicine.anatomical_structure
Lipotoxicity
Hepatocyte
ER stress
DNA Replication
medicine.medical_specialty
MAP Kinase Signaling System
Regulatory Factor X Transcription Factors
Biology
Diet
High-Fat
Taurochenodeoxycholic Acid
Stress
Physiological
Cyclins
Proliferating Cell Nuclear Antigen
Internal medicine
medicine
Animals
Hepatectomy
RNA
Messenger
Cyclin B1
Cell Proliferation
Original Article—Liver
Pancreas
and Biliary Tract
Regeneration (biology)
Forkhead Box Protein M1
Hepatology
medicine.disease
Liver Regeneration
Mice
Inbred C57BL
Hepatocytes
Unfolded Protein Response
Cancer research
Steatosis
Cyclin A2
Proto-Oncogene Proteins c-akt
Transcription Factors
Zdroj: Journal of Gastroenterology
ISSN: 1435-5922
0944-1174
DOI: 10.1007/s00535-013-0780-7
Popis: 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.
Databáze: OpenAIRE
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