title: Melatonin ameliorates ER stress-mediated hepatic steatosis through miR-23a in the liver.
abstract: The endoplasmic reticulum (ER) stress induces hepatic steatosis and inflammation in the liver. Although melatonin ameliorates ER stress-target genes, it remains unknown whether melatonin protects against hepatic steatosis as well as inflammation through regulation of miRNA. MicroRNAs have been identified as pivotal regulators in the field of gene regulation and their dysfunctions are a common feature in a variety of metabolic diseases. Especially, among miRNAs, miR-23a has been shown to regulate ER stress. Herein, we investigated the crucial roles of melatonin in hepatic steatosis and inflammation in vivo. Tunicamycin challenge caused increase of hepatic triglyceride and intracellular calcium levels through activation of ER stress, whereas these phenomena were partially disrupted by melatonin. We also demonstrated that expression of miR-23a stimulated with tunicamycin was rescued by melatonin treatment, resulting in reduced ER stress in primary hepatocytes. Overall, these results suggest a new function of melatonin that is involved in ameliorating ER stress-induced hepatic steatosis and inflammation by attenuating miR-23a. Melatonin may be useful as a pharmacological agent to protect against hepatic metabolic diseases due to its ability to regulate expression of miR-23a.
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Seung-Jae
authors: SJ
authors: Kim
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Hye Suk
authors: HS
authors: Kang
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Jae-Ho
authors: JH
authors: Lee
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Jae-Hyung
authors: JH
authors: Park
authors: Metabolism and Nutrition Research Group, Korea Food Research Institute, Seongnam, South Korea.
authors: Chang Hwa
authors: CH
authors: Jung
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Jae-Hoon
authors: JH
authors: Bae
authors: Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon 406-840, South Korea.
authors: Byung-Chul
authors: BC
authors: Oh
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Dae-Kyu
authors: DK
authors: Song
authors: Dept of Microbiology, Keimyung University School of Medicine, Daegu 704-701, South Korea.
authors: Won-Ki
authors: WK
authors: Baek
authors: Dept of Physiology, Keimyung University School of Medicine, Daegu 704-701, South Korea. Electronic address: ssim73@kmu.ac.kr.
authors: Seung-Soon
authors: SS
authors: Im
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D002460:Cell Line; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050155:Lipogenesis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000627:therapeutic use*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014415:Tunicamycin
chemical_list: D000975:Antioxidants; D035683:MicroRNAs; C534062:Mirn23b microRNA, mouse; D017382:Reactive Oxygen Species; D014415:Tunicamycin; D008550:Melatonin
keywords: Calcium; ER stress; Hepatic steatosis; Melatonin; miR-23a