INS and obesity due to melanocortin 4 receptor deficiency: As indicated in the following discussion, the restoration of impaired metabolic flexibility or the ability to effectively oxidize carbohydrate in the fed condition and change to burning fat in the fasted condition was attested by reduced weight gain, decreased obesity-related metabolic biomarkers (e.g., insulin, leptin, and total cholesterol in plasma and triacylglycerol in liver), increased adiponectin, and reestablishment of diurnal oscillation of RER by TRF.