RESUMEN
Mitochondria transplantation has emerged as a successful therapeutic modality to treat several degenerative diseases. However, the biodistribution of transplanted mitochondria has not been well studied. We investigated the ex-vivo systemic biodistribution and therapeutic efficacy of intravenously transplanted graphene quantum dots (GQDs) conjugated to isolated mitochondria (Mt-GQDs) in diabetic rat tissues. The results revealed that Mt-GQDs facilitate the tracking of transplanted mitochondria without affecting their therapeutic efficacy. It is compelling to note that Mt-GQDs and isolated mitochondria show comparable therapeutic efficacies in decreasing blood glucose levels, oxidative stress, inflammatory gene expressions, and restoration of different mitochondrial functions in pancreatic tissues of diabetic rats. In addition, histological section examination under a fluorescence microscope demonstrated the localization of Mt-GQDs in multiple tissues of diabetic rats. In conclusion, this study indicates that Mt-GQDs provide an effective mitochondrial transplantation tracking modality.
RESUMEN
AIM: We investigated the effect of mitochondria transfer in high fat diet and streptozotocin (HFD + STZ) induced metabolic syndrome (MeS) in rats. The effect of mitochondria transfer in MeS with co-existing hypertension, hyperlipidaemia, diabetes and fatty liver together, has not been reported. MATERIALS AND METHODS: Heathy mitochondria was transferred intravenously and the effect on several physiological parameters and biochemical parameters were examined in HFD + STZ rats. In addition, RNA-sequencing of healthy liver tissues was performed to elucidate the molecular pathways affected by mitochondria transfer in restoring metabolic health. KEY FINDINGS: We observed reduction in both systolic and diastolic blood pressure levels, reduced blood glucose levels, and a marked reduction in serum lipid profiles. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) also improved along with evident restoration of liver morphology demonstrated by histopathological analysis. Enhanced mitochondrial biogenetics and reduction in oxidative stress and inflammatory markers was also observed. The pathway enrichment analysis revealed reduction in insulin resistance, inflammatory markers, regulation of mitochondrial bioenergetics, calcium ion homeostasis, fatty-acid ß-oxidation, cytokine immune regulators, and enhanced lipid solubilisation. The significant effect of healthy mitochondria transfer in restoration of metabolic functions was observed by the activation of PI3K-AKT, AMPK/mTOR pathways and cytokine immune regulators, suggesting that inflammatory mediators were also significantly affected after mitochondria transfer. SIGNIFICANCE: This study, provides insights on molecular processes triggered by mitochondria transfer in fatty liver regeneration and improvement of overall metabolic health.