UBE3A and obesity due to melanocortin 4 receptor deficiency: Indeed, Ube3a+/– mice are prone to HFD-induced obesity andfatty liver development, suggesting an antagonistic role of UBE3Ain obesity-related pathogenesis.35 Mechanistically,a recent report from Kim et al. demonstrated that UBE3A suppresseslipogenic gene expression by targeting the histone methyltransferaseMLL4 for ubiquitination and degradation, resulting in the inhibitionof hepatic steatosis.35 We found that HFDfeeding down-regulates the UBE3A level in the mouse liver, suggestingthe sensitivity of UBE3A to over nutritional conditions (Figure 4).