Shusei Yamamoto1, Ikumi Sato1, Natsuki Fukuhama2, Natsumi Akiyama2, Miku Sakai2, Shota Kumazaki1, Shang Ran3, Satoshi Hirohata1, Kazuya Kitamori4, Yukio Yamori5, Shogo Watanabe6. 1. Department of Medical Technology, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. 2. Department of Medical Technology, Faculty of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. 3. Advanced Institute for Medical Sciences, Dalian Medical University, No.9 West Section Lvshun South Road, Dalian, Liaoning Province 116-044, China. 4. College of Human Life and Environment, Kinjo Gakuin University, 2-1723, Omori, Moriyama-ku, Nagoya-shi, Aichi 463-8521, Japan. 5. Institute for World Health Development, Mukogawa Women's University, 4-16, Edagawa-cho, Nishinomiya-shi, Hyogo 663-8143, Japan. 6. Department of Medical Technology, Graduate School of Health Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama-shi, Okayama 700-8558, Japan. Electronic address: watanabe1224@okayama-u.ac.jp.
Abstract
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.
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 NASHpatients. 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.