miR-10c Targets dgat2 and Affects the Expression of Genes Involved in Fatty Acid and Triglyceride Metabolism in Oreochromis niloticus Under Heat Stress

miR-10c靶向dgat2并影响热应激下尼罗罗非鱼脂肪酸和甘油三酯代谢相关基因的表达

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Abstract

Heat stress induces metabolic adaptations in fish, including the regulation of triglyceride (TG) synthesis/degradation to preserve cellular lipid balance and energy homeostasis. Diacylglycerol acyltransferase (DGAT) catalyzes the final step in TG synthesis. However, the molecular mechanisms by which DGAT regulates TG metabolism in heat-stressed fish remain unexplored. Our previous study suggested that miR-10c regulates dgat2 expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus) under heat stress. Here, we characterized the GIFT miR-10c precursor as a 65-nucleotide transcript yielding a 22 nt mature miRNA (oni-miR-10c). A phylogenetic analysis revealed a high level of miR-10c sequence conservation across species. A dual-luciferase reporter assay confirmed dgat2 as a direct target of miR-10c. Overexpression of miR-10c in vivo down-regulated dgat2 transcripts and DGAT2 protein. SiRNA-knockdown of dgat2 resulted in upregulation of cpt1α, fas, and lpl and downregulation of hsl, thereby reprogramming lipid metabolism in GIFT hepatocytes. Thus, the miR-10c-dgat2 regulatory axis facilitates TG hydrolysis and promotes fatty acid metabolism under heat stress. Our findings highlight miR-10c's potential as a dgat2 inhibitor and its function in regulating lipid metabolism in heat-stressed GIFT. Our study reveals a key molecular pathway mediating thermal adaptation of energy metabolism in fish, providing novel targets for preventing heat-induced metabolic disorders.

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