Forced expression of Smads2/3/4, but not MPK38-mediated phosphorylation-defective Smad mutants, induced a significant increase in ASK1/TGF-β/p53 signaling activation (Supplementary Fig. 4) and ameliorated glucose and lipid metabolism (Figs. 5 and 6) in HFD-fed mice versus uninfected mice fed a HFD, whereas Ad-Smad7 infection decreased ASK1/TGF-β/p53 signaling and further worsened the impaired glucose and lipid metabolism in a MPK38 phosphorylation-dependent manner. Here, SMAD7 is linked to infection.