Abstract: Exosomes were obtained by cultivating hypothalamic neural stem cells from fat-1 transgenic mice and total RNA was extracted from them for high-throughput sequencing. To study the regulatory effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on exosomal miRNAs derived from neural stem cells in the hypothalamus, and to explore the mechanism of action of n-3 PUFAs in inhibiting hypothalamic inflammation and obesity, the hypothalamic neural stem cells from fat-1 transgenic mice and wild-type C57BL/6 mice were cultured, separately. Exosomes were collected from the cell culture supernatant for total RNA extraction. After high-throughput sequencing, bioinformatics was used to analyze the differentially expressed miRNAs and predict the target genes. The target genes were analyzed by KEGG (Kyoto encyclopedia of genes and genomes) enrichment analysis and their relative expression levels were detected by quantitative real-time polymerase chain reaction (qPCR). The results showed that compared with wild-type C57BL/6 mice, the exosome miRNAs derived from hypothalamic neural stem cells in fat-1 transgenic mice had distinctive expression profiles, and the target genes of the miRNAs that were significantly differentially expressed were at key positions in the hypothalamic inflammation and fatty acid metabolism pathways. As validated by qPCR, the expression of the key target genes that were differentially expressed were regulated by n-3 PUFAs. In conclusion, the increase of endogenous n-3 PUFAs level can regulate the expression of miRNAs in exosomes from neural stem cells in the hypothalamus and the expression of genes related to inflammatory response and lipid metabolism, thereby inhibiting hypothalamic inflammation and resisting obesity.

Key words: endogenous n-3 polyunsaturated fatty acids; exosome; miRNA; hypothalamic inflammation; lipid?metabolism