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Long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in a mouse model of non-alcoholic fatty liver disease.
Toxicol Lett. 2020 Oct 10; 332:1-6.TL

Abstract

Non-alcoholic fatty liver disease (NAFLD) can be typically classified into two subgroups: non-alcoholic fatty liver and non-alcoholic steatohepatitis. Mouse models of NAFLD are useful tools for understanding the pathogenesis and progression of NAFLD and for developing drugs for its treatment. Here, we investigated the time-dependent changes in serum lipids and biochemical markers of hepatic function, hepatic inflammation, and fibrosis in mice fed a normal diet (ND) or a NAFLD diet (choline deficient, L-amino acid-defined, high-fat diet; CDAHFD) for 12 weeks. CDAHFD-fed mice showed significantly reduced serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol throughout the treatment period compared with ND-fed mice. The changes in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and total bilirubin showed an inverse U-shaped curve in the CDAHFD-fed mice. The serum alkaline phosphatase levels decreased in both ND- and CDAHFD-fed mice in a time-dependent manner. Furthermore, CDAHFD-fed mice showed a significant increase in the number of inflammatory foci and hepatic fibrosis at 6-12 weeks, although inflammatory foci and hepatic fibrogenesis were observable at relatively early stages as well (1-4 weeks). In conclusion, the long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in CDAHFD-fed mice identified in this study may provide a better understanding of NAFLD pathogenesis.

Authors+Show Affiliations

Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, 563-8577, Japan; AIST-Osaka University Advanced Photonics and Biosensing Open Innovation Laboratory, AIST, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan. Electronic address: toita-r@aist.go.jp.Division of Biopharmaceutics and Pharmacokinetics, National Cerebral and Cardiovascular Center Research Institute, 6-1 Shinmachi, Kishibe, Suita, Osaka, 564-8565, Japan. Electronic address: jrjhkang@ncvc.go.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32579995

Citation

Toita, Riki, and Jeong-Hun Kang. "Long-term Profile of Serological Biomarkers, Hepatic Inflammation, and Fibrosis in a Mouse Model of Non-alcoholic Fatty Liver Disease." Toxicology Letters, vol. 332, 2020, pp. 1-6.
Toita R, Kang JH. Long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in a mouse model of non-alcoholic fatty liver disease. Toxicol Lett. 2020;332:1-6.
Toita, R., & Kang, J. H. (2020). Long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in a mouse model of non-alcoholic fatty liver disease. Toxicology Letters, 332, 1-6. https://doi.org/10.1016/j.toxlet.2020.06.020
Toita R, Kang JH. Long-term Profile of Serological Biomarkers, Hepatic Inflammation, and Fibrosis in a Mouse Model of Non-alcoholic Fatty Liver Disease. Toxicol Lett. 2020 Oct 10;332:1-6. PubMed PMID: 32579995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in a mouse model of non-alcoholic fatty liver disease. AU - Toita,Riki, AU - Kang,Jeong-Hun, Y1 - 2020/06/21/ PY - 2020/02/13/received PY - 2020/06/16/revised PY - 2020/06/19/accepted PY - 2020/6/25/pubmed PY - 2020/9/15/medline PY - 2020/6/25/entrez KW - Animal model KW - Hepatic fibrosis KW - Hepatic inflammation KW - Non-alcoholic fatty liver disease KW - Non-alcoholic steatohepatitis KW - serum biomarker SP - 1 EP - 6 JF - Toxicology letters JO - Toxicol Lett VL - 332 N2 - Non-alcoholic fatty liver disease (NAFLD) can be typically classified into two subgroups: non-alcoholic fatty liver and non-alcoholic steatohepatitis. Mouse models of NAFLD are useful tools for understanding the pathogenesis and progression of NAFLD and for developing drugs for its treatment. Here, we investigated the time-dependent changes in serum lipids and biochemical markers of hepatic function, hepatic inflammation, and fibrosis in mice fed a normal diet (ND) or a NAFLD diet (choline deficient, L-amino acid-defined, high-fat diet; CDAHFD) for 12 weeks. CDAHFD-fed mice showed significantly reduced serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol throughout the treatment period compared with ND-fed mice. The changes in aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and total bilirubin showed an inverse U-shaped curve in the CDAHFD-fed mice. The serum alkaline phosphatase levels decreased in both ND- and CDAHFD-fed mice in a time-dependent manner. Furthermore, CDAHFD-fed mice showed a significant increase in the number of inflammatory foci and hepatic fibrosis at 6-12 weeks, although inflammatory foci and hepatic fibrogenesis were observable at relatively early stages as well (1-4 weeks). In conclusion, the long-term profile of serological biomarkers, hepatic inflammation, and fibrosis in CDAHFD-fed mice identified in this study may provide a better understanding of NAFLD pathogenesis. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/32579995/Long_term_profile_of_serological_biomarkers_hepatic_inflammation_and_fibrosis_in_a_mouse_model_of_non_alcoholic_fatty_liver_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-4274(20)30293-9 DB - PRIME DP - Unbound Medicine ER -