1869-P: Nonalcoholic Fatty Liver Disease and Insulin Resistance Are Associated via Xanthine Oxidoreductase Activity

Abstract

Xanthine oxidoreductase (XOR), which is mainly produced by the liver, has been reported to be associated with insulin resistance in addition to disorder of uric acid metabolism, which is common in obese people. Moreover, nonalcoholic fatty liver disease (NAFLD) is known to trigger insulin resistance, but the mechanism has not been sufficiently elucidated. In this study, we used FibroScan equipped with controlled attenuation parameter (CAP) estimation to measure intrahepatic fat accumulation and to evaluate the association of insulin resistance with intrahepatic fat accumulation and XOR activity by adjusting for the effects of visceral fat. Of the 200 individuals who had undergone health checkups at our medical center, 142 individuals (59 men) were included in the study after excluding 58 individuals because of incomplete data, habitual alcohol consumption, or ongoing treatment with hypoglycemic and antihyperuricemic agents. NAFLD was defined as a CAP value ≥236 dB/m. Plasma XOR activity was measured by liquid chromatography-triple quadrupole mass spectrometry using [13C2, 15N2] xanthine as a stable isotope substrate developed by Sanwa Kagaku Kenkyusho Co., Ltd. The association of insulin resistance (HOMA-IR ≥2.5) with NAFLD was analyzed by multivariate logistic analysis while adjusting the effects of other factors. NAFLD, as well as visceral fat area, were found to be an independent explanatory factor for insulin resistance. However, when logarithmic values of XOR activity levels (ln-XOR) were added to the analysis model, ln-XOR, but not NAFLD, was a significant explanatory factor for insulin resistance (odds ratio [95% confidence interval]: 4.36 [2.21-8.60]). This finding suggested that XOR of the liver was involved in the association between NAFLD and insulin resistance. In conclusion, NAFLD and insulin resistance are associated via XOR Activity. Disclosure S. Fukumoto: Research Support; Self; Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi K.K. M. Kurajoh: None. T. Nakamura: None. T. Murase: None. Y. Kakutani: None. Y. Yamazaki: None. A. Ochi: None. K. Motoyama: None. T. Morioka: Research Support; Self; Eli Lilly and Company, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Roche Diagnostics K.K., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Other Relationship; Self; Ono Pharmaceutical Co., Ltd. T. Shoji: Research Support; Self; Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Kissei Pharmaceutical Co., Ltd., Kowa, Kyowa Hakko Kirin Co., Ltd. M. Emoto: Research Support; Self; Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical CO., Ltd., Takeda Pharmaceutical Company Limited. M. Inaba: None. Funding Japan Society for the Promotion of Science