Abstract
Nonalcoholic fatty liver disease (NAFLD) is the common disease in the liver, which is associated with metabolic syndrome and hepatocellular carcinoma. Accumulated evidence establishes that small non-coding microRNAs (miRNAs) contribute to the initiation and progression of NAFLD. However, the molecular repertoire of miRNA in NAFLD is still largely unknown. Here, using an integrative approach spanning bioinformatic analysis and functional approaches, we demonstrate that miR-124-3p participates in the development of NAFLD by directly targeting preadipocyte factor-1 (Pref-1). In response to high-fat diet (HFD), expression of miR-124-3p was increased in the liver. Inhibition of miR-124-3p expression led to a dramatic reduction of triglyceride contents in hepatocytes, in parallel with decreased inflammatory factors. Mechanistically, miR-124-3p directly controls the transcription of Pref-1, a secretory factor that has been proved to resist metabolic syndrome. Our work identifies a novel molecular axis in hepatosteatosis, and highlights miR-124-3p/Pref-1 as potential targets for clinical interventions of NAFLD.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, which is characterized by excessive hepatic fat deposition and a wide range of pathologies encompassing steatohepatitis, fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma [1, 2]
Hepatic miR-122 affects gene expressions in cholesterol and lipid metabolism, and thereby maintains liver homeostasis [10, 11]. miR-27a attenuated hepatic de novo lipogenesis and alleviated obesity-initiated NAFLD by inhibiting Fasn and Scd1 in liver [12]. miR-375 is up-regulated in NASH patients, and its inhibition ameliorates lipid accumulation and decreases inflammatory cytokines [13, 14]
MiR-124-3p Expression Is Increased by high-fat diet (HFD)-Induced Hepatosteatosis
Summary
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease, which is characterized by excessive hepatic fat deposition and a wide range of pathologies encompassing steatohepatitis, fibrosis, cirrhosis, liver failure, and hepatocellular carcinoma [1, 2]. MiRNAs are emerging as new regulators of glucose and lipid metabolism during liver development and disease progression, including NAFLD [8, 9]. MiR-375 is up-regulated in NASH patients, and its inhibition ameliorates lipid accumulation and decreases inflammatory cytokines [13, 14]. MiR-27a attenuated hepatic de novo lipogenesis and alleviated obesity-initiated NAFLD by inhibiting Fasn and Scd in liver [12]. Despite these studies, the molecular repertoire of miRNA in NAFLD is still largely unknown
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