Sirt3 activation by honokiol improved fatty acid oxidation and renal function while reducing fatty acid deposition in wild-type mice with cisplatin-induced AKI, but not in Sirt3-defective mice.
Does Sirt3 activation by honokiol improve renal function and fatty acid oxidation in a murine model of cisplatin-induced AKI?
Sirt3 activation protects against cisplatin-induced acute kidney injury by improving fatty acid oxidation and mitochondrial function.
Fatty acid oxidation (FAO) dysfunction is one of the important mechanisms of renal fibrosis. Sirtuin 3 (Sirt3) has been confirmed to alleviate acute kidney injury (AKI) by improving mitochondrial function and participate in the regulation of FAO in other disease models. However, it is not clear whether Sirt3 is involved in regulating FAO to improve the prognosis of AKI induced by cisplatin. Here, using a murine model of cisplatin-induced AKI, we revealed that there were significantly FAO dysfunction and extensive lipid deposition in the mice with AKI. Metabolomics analysis suggested reprogrammed energy metabolism and decreased ATP production. In addition, fatty acid deposition can increase reactive oxygen species (ROS) production and induce apoptosis. Our data suggested that Sirt3 deletion aggravated FAO dysfunction, resulting in increased apoptosis of kidney tissues and aggravated renal injury. The activation of Sirt3 by honokiol could improve FAO and renal function and reduced fatty acid deposition in wide-type mice, but not Sirt3-defective mice. We concluded that Sirt3 may regulate FAO by deacetylating liver kinase B1 and activating AMP-activated protein kinase. Also, the activation of Sirt3 by honokiol increased ATP production as well as reduced ROS and lipid peroxidation through improving mitochondrial function. Collectively, these results provide new evidence that Sirt3 is protective against AKI. Enhancing Sirt3 to improve FAO may be a potential strategy to prevent kidney injury in the future.
Li et al. (Sun,) conducted a other in Cisplatin-induced acute kidney injury. Sirt3 activation by honokiol vs. Sirt3-defective mice was evaluated on Fatty acid oxidation, lipid deposition, apoptosis, and renal injury. Sirt3 activation by honokiol improved fatty acid oxidation and renal function while reducing fatty acid deposition in wild-type mice with cisplatin-induced AKI, but not in Sirt3-defective mice.