Although additional studies will be necessary in humans to fully characterize the complex nature and the biological significance of each sweetener, the present work demonstrated that honey has a protective effect in the development of obesity, since rats that are fed honey, showed the lowest levels of incretins, insulin, serum glucose, and leptin and the lowest stimulation of inflammatory signaling pathways. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.