Systems level analysis of lipid metabolism in oxygen-induced retinopathy [liver RNA-Seq]

Activation of anaplerosis takes away glutamine from the biosynthetic pathway to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from newly proliferating endothelial cells impeding physiological angiogenesis and leading to vasoobliteration. Using an oxygen-induced retinopathy (OIR) mouse model, we investigated the metabolic differences between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains at system levels to understand the molecular underpinnings that potentially contribute to hyperoxia-induced vascular abnormalities in the neural retina. Our systems level in vivo RNA-seq, proteomic, and lipidomic profiling and ex-vivo explant studies show that the medium-chain fatty acids serves as an alternative source to feed the TCA cycle. Our findings strongly implicate that medium-chain fatty acids could suppress glutamine-fueled anaplerosis and ameliorate hyperoxia-induced vascular abnormalities in conditions such as retinopathy of prematurity. Overall design: 12 days old OIR hyperoxia and normoxic mouse livers from OIR resistant and susecptible strains were compared to find out metabolic changes responsible to protect against OIR