To investigate whether TFE3 is sufficient to mitigate HFD‐induced obesity and diabetes, we overexpressed TFE3 in the liver of WT mice by intravenous injection of the virus expressing the human TFE3 under the control of a promoter mainly expressed in the liver (HDAd‐PEPCK‐TFE3) and fed them with a HFD for 12 weeks. Here, PCK2 is linked to obesity due to melanocortin 4 receptor deficiency.