Consistently, β-cell specific LSD1 deletion physiologically and epigenetically phenocopies the HF diet state: basal hyperinsulinemia, impaired GSIS and activation of a ‘stressed/immature’ gene signature (i.e., hexokinase1 [Hk1], 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 [Pfkfb3], jun proto-oncogene [Jun], fos proto-oncogene [Fos], nuclear factor, interleukin 3 regulated [Nfil3]). Here, PFKFB3 is linked to hydrops fetalis.