To investigate whether increased RSPO1 in adipose tissue can induce obesity, we generated an aP2 promoter‐driven human RSPO1 (hRSPO1) transgenic mouse model (hRSPO1Tg) in which hRSPO1 was effectively overexpressed in three adipose tissues (Figure S3A,B, Supporting Information). This evidence concerns the gene RSPO1 and obesity due to melanocortin 4 receptor deficiency.