In adult HFD-fed mice, cytosolic delivery of mtRNA into the inguinal adipose tissue depot, combined with Vit-D3 treatment, reduced Irf7 levels (and not Irf3 levels) and increased beige adipocyte content (Fig. 5h and Extended Data Fig. 7a), alleviated obesity and adipocyte inflammation and increased mitochondrial mass, thermogenesis and energy expenditure (Fig. 5h–j and Extended Data Figs. 7b,c and 8). Here, IRF3 is linked to obesity disorder.