TY - JOUR
T1 - Bile acids aggravate nonalcoholic steatohepatitis and cardiovascular disease in SHRSP5/Dmcr rat model
AU - Yamamoto, Shusei
AU - Sato, Ikumi
AU - Fukuhama, Natsuki
AU - Akiyama, Natsumi
AU - Sakai, Miku
AU - Kumazaki, Shota
AU - Ran, Shang
AU - Hirohata, Satoshi
AU - Kitamori, Kazuya
AU - Yamori, Yukio
AU - Watanabe, Shogo
N1 - Funding Information:
This work was supported by grants from the Japan Society for the Promotion of Science Grant-in-Aid for Young Scientists (B), Grant Number 15K19178 and Grant-in-Aid for Scientific Research (C), Grant Number 18K10993 to S. Watanabe.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Background and aims: Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model. Method and results: From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group. Conclusion: In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.
AB - Background and aims: Nonalcoholic steatohepatitis (NASH) is linked to an increased risk of cardiovascular disease, regardless of the risk factors in metabolic syndrome. However, the intermediary factors between NASH and cardiovascular disease are still unknown. A previous study revealed that serum and hepatic bile acid (BA) levels are increased in some NASH patients. We aimed to examine whether NASH and cardiovascular disease were aggravated by BA using an animal model. Method and results: From 10 to 18 weeks of age, SHRSP5/Dmcr rats divided into 3 groups were fed 3 types of high-fat and high-cholesterol (HFC) diets which were changed in the cholic acid (CA) concentration (0%, 2%, or 4%). The nitro oxide synthase inhibition (L-NAME) was administered intraperitoneally from 16 to 18 weeks of age. The 4% CA groups showed the worst LV dysfunction and myocardial fibrosis, and demonstrated severe hepatic fibrosis and lipid depositions. In addition, a large amount of lipid accumulation was observed in the aortas of the 4% CA group, and NFκB and VCAM-1 gene expression levels were increased. These findings were not seen in the 0% CA group. Conclusion: In the SHRSP5/Dmcr rat model, NASH and cardiovascular disease were aggravated with increasing BAs concentrations in an HFC diet.
KW - Accumulation of lipid
KW - Bile acids
KW - Cardiovascular disease
KW - Nonalcoholic steatohepatitis
KW - SHRSP5/Dmcr
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U2 - 10.1016/j.yexmp.2020.104437
DO - 10.1016/j.yexmp.2020.104437
M3 - Article
C2 - 32246926
AN - SCOPUS:85082724228
VL - 114
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
M1 - 104437
ER -
