Asah2 dysfunction results in the accumulation of sphingolipid, which is demonstrated to induce decreased electron transport chain activity and ATP production, fragmentation of mitochondria, ROS production, and chronic oxidative stress in obesity and type 2 diabetes [27,55,56], which is similar to our findings in ISCs. This evidence concerns the gene ASAH2 and obesity due to melanocortin 4 receptor deficiency.