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Background:  Long-term high-fat diet (HFD) feeding, which can induce obesity, can also induce nonalcoholic steatohepatitis (NASH) and liver tumorigenesis. A previous study reported that concentrated Kurozu (CK) supplementation reduced the incidence of HFD-induced hepatic steatosis in mice. It was showed that CK supplementation improved dyslipidemia in animal and clinical study. Small noncoding RNAs, micro RNAs (miRs), play crucial roles in the biology of cell functions, lipid metabolism and neoplasms. However, the effect of CK treatment on the relationship between HFD and expression of miRs is unclear.   Objective:  To evaluate changes in the expression of hepatic miRs and lipid metabolism- associated genes on administering a HFD for 60 weeks in C57BL6J mice. The onset of hepatic steatosis induced by HFD treatment was also observed.   Methods:  The mice received a HFD, HFD with CK, or standard diet (SD) for 60 consecutive weeks. The effect of CK treatment on the expression levels of lipid metabolism-associated genes in the liver was evaluated.   Results:  HFD feeding significantly increased expression of  Tnf , and significantly decreased  Adipoq  and  Mlxipl  in the liver. The ingestion of CK elevated the expression levels of  Pgc-1α  and  Igfbp1  in the liver compared with the SD group. HFD feeding significantly increased the expression of  miR-488-5p , and significantly decreased  miR-29b  and - 122a-5p  in the liver. The ingestion of CK elevated the expression levels of  miR-34a , - 149-3p , and - 181a-5p  in the liver compared with the SD group. Expression levels of  miR-488-3p  in the serum HFD group were significantly higher than in the SD group. The ingestion of CK elevated the expression levels of  miR-181a-5p  in the serum compared with the SD group.   Conclusion:  These results suggest that CK supplementation reduced the onset of hepatic hyperplasia, and increased hepatic  miR-34a , - 149-3p , and - 181a-5p . These miRs may function as suppressors of tumors caused by HFD feeding.   Key Words :  High-fat diet, carcinogenesis, Kurozu, microRNA, miR-34a, miR-122a-5p, miR-149, miR-181a, miR-488

Effect of concentrated Kurozu, a traditional Japanese vinegar, on expression of hepatic miR-34a, -149-3p, and -181a-5p in high-fat diet-fed mice