In support of these previous observations, the use of cell type–specific conditional genetic ablation of iPLA2γ in conjunction with high-resolution respirometry of isolated mitochondria and analysis of hepatic eicosanoids suggest that HF feeding induces 12-HETE–mediated mitochondrial dysfunction which is initiated by the activation of hepatic iPLA2γ to generate nonesterified AA or arachidonoyl-lysolipids which serve as substrate(s) for 12-LOX. The gene discussed is ALOX12; the disease is hydrops fetalis.