Our previous study indicated that 3 months of consumption of H2-water improved obesity (body-fat weight) and diabetes (glucose, insulin, and triglycerides) in db/db mice accompanied by increased expression of the FGF21 gene; however, the causal association among their improved phenotypes, stimulated energy metabolism, and gene expression was unclear because of their long-term mutual interactions. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.