ISG15 and hepatocellular carcinoma: The mRNA level of Irf3 in HCC tissues was downregulated in HFD‐fed mice (Figure 2A), with a trend toward decreased protein levels (Figure 2B,C), in agreement with previous reports that hepatic Irf3 is downregulated by HFD‐feeding.[28, 29, 30] Moreover, we did not observe a significantly altered phosphorylated Irf3 level in HCC tissues between HFD‐ and NCD‐fed groups (Figure 2C), suggesting that Irf3 may not play a major role in upregulating hepatic Isg15 in HFD‐fed mice.