In conclusion, our study presents a strategy to alleviate the burden of obesity and reduce the risk of adiposity-related complications (e.g., NAFLD) by an ER stress- and oxidative stress- relieving nano-platform KT-NE to scavenge excessive ROS and restrain XBP1 hyperactivation in adipose tissues. This evidence concerns the gene XBP1 and obesity due to melanocortin 4 receptor deficiency.