title: MicroRNA profiles following metformin treatment in a mouse model of non-alcoholic steatohepatitis.
abstract: Non-alcoholic steatohepatitis (NASH) is one of the most common causes of chronic liver disease and is considered to be a causative factor of cryptogenic cirrhosis and hepatocellular carcinoma. microRNAs (miRNAs) are small non-coding RNAs that negatively regulate messenger RNA (mRNA). Recently, it was demonstrated that the aberrant expression of certain miRNAs plays a pivotal role in liver disease. The aim of the present study was to evaluate changes in miRNA profiles associated with metformin treatment in a NASH model. Eight-week-old male mice were fed a methionine- and choline-deficient (MCD) diet alone or with 0.08% metformin for 15 weeks. Metformin significantly downregulated the level of plasma transaminases and attenuated hepatic steatosis and liver fibrosis. The expression of miRNA-376a, miRNA‑127, miRNA-34a, miRNA-300 and miRNA-342-3p was enhanced among the 71 upregulated miRNAs, and the expression of miRNA-122, miRNA-194, miRNA-101b and miRNA-705 was decreased among 60 downregulated miRNAs in the liver of MCD-fed mice when compared with control mice. Of note, miRNA profiles were altered following treatment with metformin in MCD-fed mice. miRNA-376a, miRNA‑127, miRNA-34a, miRNA-300 and miRNA-342-3p were downregulated, but miRNA-122, miRNA-194, miRNA‑101b and miRNA-705 were significantly upregulated in MCD-fed mice treated with metformin. miRNA profiles were altered in MCD-fed mice and metformin attenuated this effect on miRNA expression. Therefore, miRNA profiles are a potential tool that may be utilized to clarify the mechanism behind the metformin-induced improvement of hepatic steatosis and liver fibrosis. Furthermore, identification of targetable miRNAs may be used as a novel therapy in human NASH.
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Akiko
authors: A
authors: Katsura
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Asahiro
authors: A
authors: Morishita
authors: Life Science Research Center, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Hisakazu
authors: H
authors: Iwama
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Joji
authors: J
authors: Tani
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Teppei
authors: T
authors: Sakamoto
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Miwa
authors: M
authors: Tatsuta
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Yuka
authors: Y
authors: Toyota
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Koji
authors: K
authors: Fujita
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Kiyohito
authors: K
authors: Kato
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Emiko
authors: E
authors: Maeda
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Takako
authors: T
authors: Nomura
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Hisaaki
authors: H
authors: Miyoshi
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Hirohito
authors: H
authors: Yoneyama
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Takashi
authors: T
authors: Himoto
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Shintaro
authors: S
authors: Fujiwara
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Hideki
authors: H
authors: Kobara
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Hirohito
authors: H
authors: Mori
authors: Department of Immunology and Immunopathology, Kagawa University School of Medicine, Kita-gun, Kagawa.
authors: Toshiro
authors: T
authors: Niki
authors: Department of Gastroenterology and Hepatology, Kochi Medical School, Koichi, Japan.
authors: Masafumi
authors: M
authors: Ono
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Mitsuomi
authors: M
authors: Hirashima
authors: Department of Gastroenterology and Neurology, Kagawa University School of Medicine, Kita-gun, Kagawa, Japan.
authors: Tsutomu
authors: T
authors: Masaki
mesh_terms: D000818:Animals; D002796:Choline Deficiency; D016000:Cluster Analysis; D004032:Diet; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D008715:Methionine / Q000172:deficiency; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D008687:Metformin; D008715:Methionine