Thus, HFD feeding leading to incomplete beta oxidation and accumulation of long and medium chain acylcarnitines or increased efflux of short chain acylcarnitines from the mitochondria may play a contributory role in the development of obesity and insulin resistance in the skeletal muscle through retrograde communication to regulate NEMG expression and mitochondrial adaptations. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.