Grass carp (Ctenopharyngodon idella) is one of the most important cultured fish in China, and it is popular with consumers because of its delicious flesh. In order to reduce the cost of aquaculture, high-fat diet (HFD) is widely used because of its protein sparing action [[1], [2], [3], [4]]. However, when the fat intake exceeds the upper tolerance limit of grass carp, the normal lipid metabolism will be disordered, thus limiting fish growth [[5], [6], [7], [8]]. It is one of the urgent problems to be solved in aquaculture to reduce the adverse effects caused by HFD.

Selenium (Se) is an essential element for humans and animals. Furthermore, a moderate amount of Se can improve antioxidant capacity [[9], [10], [11]], alleviate lipid metabolism disorders, and promote growth [12,13]. Previous study showed that the addition of appropriate amounts of Se reduced hepatocyte lipid accumulation and alleviated lipid metabolism disorders caused by high-sugar diets and HFD in rats [13]. Our recent studies also showed that 0.3–0.6 mg/kg of nano-Se significantly alleviated lipid accumulation and liver injury induced by HFD in grass carp [14], and sodium selenite reduced the lipid accumulation induced by oleic acid (OA) in grass carp hepatocytes [15]. However, the mechanism of selenium alleviating lipid accumulation is still unclear, which needs further exploration.

The microRNAs (miRNAs), a class of ∼22 nt noncoding RNA, are widely involved in regulating animal physiological metabolism [16] Exosome (exo) is a kind of extracellular vesicles secreted by various cell types and consists of a lipid bilayer with a diameter of 30-100 nm. It contains bioactive substances, such as proteins, lipids, and genetic material (e.g., miRNAs, lncRNAs), and plays a role in intercellular communication [17]. Many studies revealed that miR-22 is associated with lipid and metabolic homeostasis [18,19]. The research proved that miR-22 deficiency accelerated liver lipid accumulation in mice [20] and miR-22 overexpression inhibited muscle lipid synthesis [21], but some studies showed the opposite results [22,23]. The role of miR-22 in lipid metabolism may differ depending on tissue and physiological state. Exosomal miRNAs have been found to play a role in regulating lipid metabolism in animals [[24], [25], [26]]. However, the effect of exosome-derived miR-22 on lipid metabolism in hepatocytes is still unclear. In addition, Se addition to the diet significantly affects the expression profile of miRNAs in animals, and miRNAs play an important factor in the antioxidant function of Se and Se-related diseases [27]. Therefore, whether Se regulates lipid metabolism via miR-22 needs to be further investigated.

Therefore, in the current study, the grass carp hepatocyte (L8824) model was employed to further explore whether exosomal miR-22 was involved in Se reducing liver lipid accumulation of grass carp fed with HFD and potential mechanisms of miR-22 regulating lipid metabolism. The results may provide new ideas for solving the problem of excessive lipid accumulation in grass carp, which has important theoretical and application significance.