In conclusion, we showed that a novel treatment with a combination of LC and NR, but not the mono-treatments, significantly attenuated obesity, fat mass, hepatic steatosis and exerted beneficial effects on metabolic control pathways and upstream regulators (ACOX, SCPAP, SREBF2, PPARGC1B, INSR) in the liver. The gene discussed is PPARGC1B; the disease is obesity due to melanocortin 4 receptor deficiency.