Moreover, renal Utx knockout not only ameliorated the HFD-induced kidney steatosis, but also prevented HFD-induced obesity and NAFLD due to increasing circulating serine level; renal-released serine prevented hepatocytes and renal tubular cells from lipid accumulation upon HFD stress (Figs. 1–3, 5, and 10 and Supplementary Figs. 1–3, 5). This evidence concerns the gene KDM6A and obesity due to melanocortin 4 receptor deficiency.