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Circulating mir-200c and mir-33a may be used as biomarkers for predicting high fructose corn syrup-induced fatty liver and vitamin D supplementation-related liver changes.

BACKGROUND
Nonalcoholic fatty liver is one of the most common forms of liver disease and role of microRNAs (miRNAs) on this illness is currently unclear. It was aimed to evaluate the predictive role of circulating miR-33a and mir-200c on high fructose corn syrup (HFCS)-induced fatty liver and vitamin D3 supplementation-related hepatic changes.


METHODS
Twenty-four rats were randomized into three groups: sham (n = 8), experimental fatty liver group (n = 8), and fatty liver + vitamin D3 supplementation group (n = 8). In the treatment group, 10 µg/kg/week of vitamin D3 was given by orogastric tube weekly for 4 weeks in addition to a high fructose diet. Serum AST, ALT, TNF-α, and MDA levels were tested. Liver tissue samples were examined using hematoxylin/eosin, periodic acid-Schif (PAS) and Masson's Trichrome staining. Circulating miR-33a and mir-200c were quantified by qRT-PCR method. Moreover, in silico analyses were accomplished.


RESULTS
In the vitamin D3 group, results of biochemical parameters were significantly different than those of the fatty liver group (p < 0.001). Moreover, significant differences in serum levels of circulating miR-33a and mir-200c were identified among all groups (p < 0.05). Finally, more favorable histopathological changes were noticed in the vitamin D3 supplementation group. The expressions of Ki-67 were also considerably reduced in the vitamin D3 group. According to KEGG pathway analysis, mir-33a and mir-200c were found to play a common role in the Hippo signaling pathway, lysine degradation, and protein processing.


DISCUSSION
Our current experimental fatty liver study showed that, in a specified dose, vitamin D3 supplementation could alleviate adverse undesirable hepatic effects of HFCS via miR-33a and mir-200c.