DHA alleviates high glucose-induced mitochondrial dysfunction in Oreochromis niloticus by inhibiting DRP1-mediated mitochondrial fission

Abstract

Dynamin-related protein 1 (DRP1) is a key regulator in the maintenance of mammalian glucose homeostasis, but the relevant information remains poorly understood on aquatic animals. In the study, DRP1 is formally described for the first time in Oreochromis niloticus. DRP1 encodes a peptide of 673 amino acid residues that contained three conserved domains: a GTPase domain, a dynamin middle domain and a dynamin GTPase effector domain. DRP1 transcripts are widely distributed in all of the detected seven organs/tissues, and the highest mRNA levels in brain. High-carbohydrate (45 %) fed fish showed a significant upregulation of liver DRP1 expression than that of control (30 %) group. Glucose administration upregulated liver DRP1 expression, with peak values observed at 1 h; then its expression returned to the basal value at 12 h. In the in vitro study, DRP1 over-expression significantly decreased mitochondrial abundance in hepatocytes. DHA significantly increased mitochondrial abundance, transcriptions of mitochondrial transcription factor A (TFAM) and mitofusin 1 and 2 (MFN1 and MFN2) and complex II and III activities of high glucose-treated hepatocyte, whereas the opposite was true for DRP1, mitochondrial fission factor (MFF) and fission (FIS) expression. Together, these findings illustrated that O. niloticus DRP1 is highly conserved, and it participated in glucose control of fish. DHA could alleviate high glucose-induced mitochondrial dysfunction of fish by inhibiting DRP1-mediated mitochondrial fission.