Therefore, the objective of this study was to determine how heterozygous knockout of GAA (HetKO‐GAA) in mice impacts metabolic health (i.e., body weight, insulin sensitivity, glucose tolerance, fatty liver) and metabolism (i.e., liver glycogen content, liver glucose output, substrate metabolism, energy expenditure, liver transcriptome) in a mouse model of high‐fat diet‐induced obesity and prediabetes. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.