Fatty hepatocyte-derived exosomal miR-122 promotes lipid synthesis and reduces immunocompetence in grass carp (Ctenopharyngodon idella)

Exosomes are nano-sized extracellular vesicles (EVs) secreted by all cell types and are a large component of the broader class of EVs, which feature a bimolecular phospholipid membrane and are critical in inter-tissue communication. Cellular crosstalk between the liver and the immune system is known to be closely mediated by exosomes. Nevertheless, information is scarce regarding the exact interaction between the lipid metabolism and inflammatory functions of exosomal microRNAs (miRNAs) in aquatic animals. The current investigation first analyzes exosomes derived from fatty hepatocytes treated with oleic acid (OA). Fatty hepatocyte-derived exo-somes (OA-Exosomes, OA-Exos) were sequenced by BGISEQ-500 sequencing technology and injected intraper-itoneally into the grass carp. A total of 298 differentially expressed miRNAs were characterized in the grass carp fatty hepatocyte exosomes, of which 132 were upregulated miRNAs and 166 were downregulated miRNAs. Among the top 9 upregulated miRNAs with the highest differential expression, miR-18a-5p, miR-144, miR-122, and miR-143 were primarily involved in lipid metabolism. AST levels were remarkably elevated in the OA-Exos group (P < 0.05), while it demonstrated swollen hepatocytes, vacuolar degeneration, and increased hepatic lipid droplets in this group, indicating that exosomes promoted the formation of fatty liver and subsequent liver injury. In addition, the lipid synthesis genes ACC, FAS, PPAR gamma and SPEBP-1 were significantly upregulated (P < 0.05), while PPAR alpha and LPL expressions were significantly downregulated (P < 0.05) after treatment with OA-Exos and miR-122 agomir. Levels of proinflammatory mediator TNF-alpha, NF-kappa B, and IL-1 beta were also upregulated in the hepatopancreatic system of grass carp that received intraperitoneal injections of OA-Exos and miR-122 agomir (P < 0.05). These results suggested that the exosome of interest and its miR-122 may promote the occurrence of fatty liver and inflammation, thus laying the foundation for further studies on lipid metabolism and immune regulation of exosomes in fish.

Automated summary

This study investigates the exact interaction between lipid metabolism and inflammatory functions of exosomal microRNAs (miRNAs) in aquatic animals. The researchers sequenced exosomes derived from fatty hepatocytes treated with oleic acid (OA) and found differentially expressed miRNAs involved in lipid metabolism and inflammation. The results suggest that these exosomes and miRNAs may promote the occurrence of fatty liver and inflammation.