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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], 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 SHRSP5/Dmcr is a useful animal model for the development of nonalcoholic steatohepatitis (NASH) pathology when fed a high-fat, high-cholesterol diet, and further drug interventions can lead to concomitant cardiovascular disease. While SHRSP5/Dmcr rats have been used for basic research related to NASH, details of their bile acid metabolism in this condition are unknown. In this study, we aimed to clarify the changes in the serum bile acid (BA) fractions associated with NASH and found that glycine-conjugated and unconjugated bile acid increased with worsening NASH and cardiovascular disease while taurine-conjugated BA relatively decreased., Competing Interests: No potential conflict of interest relevant to this article was reported.