Based on our observation that caspase-8 signaling regulated cell death and inflammatory responses in macrophages to LPS and palmitate in vitro, as well as past reports that RIPK3 and/or caspase-8 activity can regulate inflammasome-dependent and independent inflammatory responses in other disease models (Allam et al, 2014; Lawlor et al, 2015), we next investigated how loss of caspase-8 in myeloid cells impacts HFD-induced obesity and MAFLD development. The gene discussed is RIPK3; the disease is obesity due to melanocortin 4 receptor deficiency.