1. Therapeutic effect of ouabagenin, a novel liver X receptor agonist, on atherosclerosis in nonalcoholic steatohepatitis in SHRSP5/Dmcr rat model
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Yamamoto, Shusei, Sato, Ikumi, Fujii, Moe, Kakimoto, Mai, Honma, Koki, Kirihara, Sora, Nakayama, Hinako, Fukuoka, Taketo, Tamura, Satoru, Ueda, Minoru, Hirohata, Satoshi, and Watanabe, Shogo
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Models ,Health aspects ,Atherosclerosis -- Models -- Health aspects ,Cholesterol -- Health aspects -- Models ,Liver -- Health aspects -- Models - Abstract
Shogo Watanabe^orcid.org/0000-0002-1700-2892 1. Introduction Metabolic syndrome (MS) is an increasing health issue in today's society that causes lifestyle diseases, such as hypertension, diabetes, and dyslipidemia. Nonalcoholic fatty liver disease (NAFLD) [...], The liver X receptor (LXR) can enhance cholesterol transporters, which could remove excess cholesterol from foam cells in atheromas. LXR has two subtypes: LXR[alpha], which aggravates hepatic lipid accumulation, and LXR[beta], which does not. In 2018, ouabagenin (OBG) was reported as a potential LXR[beta]-specific agonist. We aimed to examine whether OBG specifically affects LXR[beta] in nonalcoholic steatohepatitis (NASH); it did not aggravate hepatic steatosis and can suppress the development of atherosclerosis. SHRSP5/Dmcr rats fed a high-fat and high-cholesterol diet were divided into four groups as follows: (I) L-NAME group, (II) L-NAME/OBG group, (III) OBG (-) group, and (IV) OBG (+) group. All groups' rats were intraperitoneally administered L-NAME. The L-NAME/OBG group's rats were intraperitoneally administered OBG and L-NAME simultaneously. After L-NAME administration, the OBG (+) group's rats were administered OBG, while the OBG (- ) group's rats were not. Although all rats developed NASH, OBG did not exacerbate steatosis (L-NAME/OBG and OBG (+) groups). In addition, endothelial cells were protected in the L-NAME/OBG group and foam cells in the atheroma were reduced in the OBG (+) group. OBG is an LXR[beta]-specific agonist and has a potential therapeutic effect on atherosclerosis without developing lipid accumulation in the liver. Key words: nonalcoholic steatohepatitis, atherosclerosis, SHRSP5/Dmcr, ouabagenin, liver X receptor [beta]
- Published
- 2023
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