In our study, the main results clearly showed that the replacement of rapid digestible CHO for slowly digestible CHO (ISR) in a HFD prevented the HFD-obesity-related adverse effects and improve lipid metabolism and glucose control through different mechanisms including regulation of hormones, such as insulin and leptin, and incretins (GLP-1), as well as the management of cellular metabolic pathways related to lipogenesis and protein homeostasis. Here, GCG is linked to obesity due to melanocortin 4 receptor deficiency.