Furthermore, HFD induces obesity and increases the number of activated M1 macrophages, leading to the development of chronic inflammation in WAT and aggravated, systemic insulin resistance.1, 36, 37 Hoxa5 is an important transcription factor that is highly expressed in adipose tissue and plays a vital role in regulating adipocytes, including their differentiation and inflammation.26, 27 In this study, we observed that Hoxa5 relieved HFD‐induced ERS in WAT, and ERS aggravates M1 macrophage activation. Here, HOXA5 is linked to Insulin resistance.