Therapeutic effects of Spirulina against experimentally-induced non-alcoholic fatty liver in rats may involve miR-21, -34a and -122

The present study was aimed to investigate the therapeutic effects of Spirulina against a rat model of high-fat-diet- induced non-alcoholic fatty liver (HFD-NAFL). The expression of mature miR-21, miR-34a and miR-122 and their targets genes; HPB1, SIRT1, and SREBP-1c; respectively were investigated as a molecular target of Spirulina. Fifty male rats were classified into two groups; negative control group (n = 10) and NAFL group (n = 40) which has been subdivided into 4 subgroups (10 rats each). One group is the untreated NAFL animals, while the other three groups were treated by oral aqueous Spirulina in a dose of 100, 200 and 500 mg/kg for 30 days. Serum AST, ALT, fasting glucose, and insulin were determined. The homeostasis model assessment index for insulin resistance (HOMA-IR) was calculated. Also, the hepatic expression of miR-21, miR-34a and miR-122 and their targets genes; HPB1, SIRT1, and SREBP-1c were assessed using real-time PCR. The NAFL animals showed marked induction of the hepatic expression of miR-21 and -34a which associated with marked suppression of their target genes; HPB1 and SIRT1; respectively. On the other hand, the expression of miR-122 showed significant suppression, while its target gene; SREBP-1c was greatly induced. The NAFL rats treated orally with different doses of Spirulina daily showed dose dependent ameliorations in body weight, liver functions, fasting blood sugar, insulin and HOMA-IR significantly. Spirulina treatment significantly and dose dependently modulate the hepatic expression of miR-21, miR-34a and miR-122 and their targets genes; HPB1, SIRT1, and SREBP-1c; respectively. Conclusion: Spirulina treatment of HFD-NAFL in rats modulated glucose, insulin sensitivity and showed anti-steatotic properties; effects that could be attributed at least partially to modulating hepatic microRNA expression. In conclusion, Spirulina can be considered as a potential anti-steatotic agent and might provide promising therapeutic approaches in NAFLD.