In our study, we showed that lifelong consumption of a diet consisting of 25% kcal from sucrose generally had no significant impact on inducing overeating and obesity and most related outcomes (blood glucose and insulin level; plasma total cholesterol and TG level; liver histopathology and gene expression; and life expectancy), compared to a 10% kcal sucrose diet. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.