TNF and obesity due to melanocortin 4 receptor deficiency: In support of this concept, direct injection of exogenous 18 carbon LPIs can rapidly (24 hr) increase the expression of genes characteristic of hepatic inflammation (Cd11c, Tnfa, IL1b) and early fibrosis (Desmin, Col1A1, Col1A2, and Acta2) in mice with Mboat7 knockdown (Figure 8 and Figure 8—figure supplement 2). These data suggest that 18 carbon LPI lipids can acutely induce hepatic inflammatory and fibrotic gene expression programs, but only when MBOAT7 function is compromised, as is seen in obesity or with loss of function variants like rs641738.