Hiroya Yamada1, Koji Ohashi2, Koji Suzuki3, Eiji Munetsuna4, Yoshitaka Ando5, Mirai Yamazaki2, Hiroaki Ishikawa2, Naohiro Ichino6, Ryouji Teradaira2, Shuji Hashimoto7. 1. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan. Electronic address: hyamada@fujita-hu.ac.jp. 2. Department of Clinical Biochemistry, Fujita Health University School of Health Sciences, Toyoake, Japan. 3. Department of Public Health, Fujita Health University School of Health Sciences, Toyoake, Japan. 4. Department of Biochemistry, Fujita Health University School of Medicine, Toyoake, Japan. 5. Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University School of Medicine, Toyoake, Japan. 6. Department of Clinical Physiology, Fujita Health University School of Health Sciences, Toyoake, Japan. 7. Department of Hygiene, Fujita Health University School of Medicine, Toyoake, Japan.
Abstract
BACKGROUND: Circulating microRNAs (miRs) may be promising biomarkers for several diseases. We previously found that miR-122 can function as a biomarker for non-alcoholic fatty liver disease (NAFLD). However, little is known regarding the time course of circulating miR-122 levels during the development of NAFLD. Here, we examined circulating miR-122 levels using a rat model of NAFLD. METHODS: To clarify changes in serum levels of miR-122 during development of NAFLD, experimental rats were fed a high-fat diet (HFD) for 2-10 weeks, while control rats received standard chow. Serum and liver tissue was collected from all animals at 2, 6, and 10 weeks of feeding. Clinical laboratory parameters (cholesterol, TG, AST, ALT, NEFA) were determined by biochemistry analyzer. Hepatic lipid accumulation was estimated by Oil red O staining. Circulating miR-122 levels were then measured by real-time polymerase chain reaction. RESULTS: Over the 10 weeks of feeding, body weight, total liver lipids, and liver and serum triacylglycerol were increased in the HFD group compared to the control group. However, no significant changes in serum alanine aminotransferase activity were observed, suggesting that NAFLD status was mild. In contrast, we observed drastic up-regulation of circulating miR-122 levels. Our findings suggest that serum miR-122 level is indeed useful for assessing early NAFLD and might be superior to clinical markers traditionally used to monitor hepatic disease.
BACKGROUND: Circulating microRNAs (miRs) may be promising biomarkers for several diseases. We previously found that miR-122 can function as a biomarker for non-alcoholic fatty liver disease (NAFLD). However, little is known regarding the time course of circulating miR-122 levels during the development of NAFLD. Here, we examined circulating miR-122 levels using a rat model of NAFLD. METHODS: To clarify changes in serum levels of miR-122 during development of NAFLD, experimental rats were fed a high-fat diet (HFD) for 2-10 weeks, while control rats received standard chow. Serum and liver tissue was collected from all animals at 2, 6, and 10 weeks of feeding. Clinical laboratory parameters (cholesterol, TG, AST, ALT, NEFA) were determined by biochemistry analyzer. Hepatic lipid accumulation was estimated by Oil red O staining. Circulating miR-122 levels were then measured by real-time polymerase chain reaction. RESULTS: Over the 10 weeks of feeding, body weight, total liver lipids, and liver and serum triacylglycerol were increased in the HFD group compared to the control group. However, no significant changes in serum alanine aminotransferase activity were observed, suggesting that NAFLD status was mild. In contrast, we observed drastic up-regulation of circulating miR-122 levels. Our findings suggest that serum miR-122 level is indeed useful for assessing early NAFLD and might be superior to clinical markers traditionally used to monitor hepatic disease.