Investigating and identifying pathogenic molecules of non-alcoholic fatty liver disease (NAFLD) has become imperative, which would serve as effective targets in the future. We established high-fat diet (HFD)-induced NAFLD model in mice and palmitic acid (PA)-induced model in mouse AML12 cells. The level of miR-218-5p was examined by qRT-PCR, and Elovl5 was identified as the potential target gene of miR-218-5p . The binding relationship between miR-218-5p and Elovl5 was validated by double luciferase reporter gene assay, and inhibition/overexpression of miR-218-5p in vitro . The functional mechanisms of miR-218-5p / Elovl5 in regulating lipogenesis in NAFLD were investigated in vivo and in vitro through gain- and loss-of-function studies. MiR-218-5p was significantly increased, and Elovl5 was decreased in model group. According to the double luciferase reporter and gene interference experiments in AML12 cells, Elovl5 was a target gene of miR-218-5p and its expression was regulated by miR-218-5p . The SREBP1-mediated lipogenesis signaling pathway regulated by Elovl5 was upregulated in model group. Moreover, silencing of miR-218-5p significantly upregulated Elovl5 expression, and suppressed SREBP1 signaling pathway in PA-induced AML-12 cells. Correspondingly, the cell injury, elevated TC, TG contents and lipid droplet accumulation were ameliorated. Furthermore, the effect of miR-218-5p on lipogenesis in vitro and in vivo was obstructed by si-Elovl5 , implicating that miR-218-5p promotes lipogenesis by targeting ELOVL5 in NAFLD. miR-218-5p could promote fatty acid synthesis by targeting Elovl5 , thereby accelerating the development of NAFLD, which is one of the key pathogenic mechanisms of NAFLD and provides a new molecular target for the management of NAFLD.
Marine hydrosphere is in grave danger if extreme weather conditions, such as high temperatures and heat waves, become the norm. The functional characteristics of nano Zn oxides (nZnO) might provide a “booster substance” that helps marine species to endure environmental stress. In the present study, physiological indicators and simulated severe environments were used to evaluate the antioxidative ability of nZnO in marine rabbitfish Siganus fuscescens, with an aim to help them resist extreme environmental stress. Rabbitfish were exposed to different diets with ZnSO4 and nZnO at the optimum requirement level (Zn content of 62.5 μg g−1), and then challenged with a low dissolved oxygen concentration and higher temperature. We demonstrated that dietary nZnO promoted the anti-oxidation defense system of the rabbitfish by improving the activities of the antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), and the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio without tissue damage. Compound stressors reduced the median survival duration of the rabbitfish from 4.25 h to 2.5 h (dietary exposure) and 9 h to 5.75 h (dietary nZnO exposure) compared to single environmental stress. nZnO downregulated the HIF gene expression and increased the prolyl hydroxylase (PHD) activity in the liver of the rabbitfish. After 10 h of extreme environmental exposure, the gene expression results indicated that nZnO inhibited the NF-κB/IL-1β/IL-6 pathway and TNF-α/Bcl-2/Bax/caspase 9 pathway and activated the akt/mTOR/elovl5 and elovl8 pathway of the rabbitfish to maintain the resilience of the fish under the extreme environment. These results strongly suggested that nZnO may improve the anti-oxidation ability of fish to resist extreme environments.
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