Understanding the underlying molecular pathways by which

摘要

Molecular pathways by which MBOAT7/LPIAT1 depletion induces hepatic steatosis. MBOAT7/LPIAT1 has an acyltransferase activity, incorporating arachidonic acid into lysophosphatidylinositol in the Lands' cycle. Xia et al. recently suggest that MBOAT7 depletion promotes an increase in de novo lipogenesis driven by the activation of SREBP-1c. In an independent work, Tanaka et al. propose that MBOAT7 depletion simultaneously causes an increased PI synthesis and PI degradation mediated by an unknown protein with PLC activity resulting in DAG, a substrate of triglyceride synthesis. These mechanisms contribute to the development of MBOAT7-induced hepatic steatosis, although they have yet to be entirely elucidated. AA, arachidonic acid; AGPAT, 1-acylglycerol-3-phosphate-O-acyltransferase; CDP-DAG, cytidine diphosphate diacylglycerol; CDS, cytidine diphosphate diacylglycerol synthase; DAG, diacylglycerol; DGAT, diacylglycerol O-acyltransferase; FA, fatty acids; G-3-P, glycerol-3-phosphate; GPAT, glycerol-3-phosphate acyltransferase; IP1, inositol monophosphate; LPA, lysophosphatidic acid; LPI, lysophosphatidylinositol; MBOAT7, membrane-bound O-acyltransferase domain–containing 7; OA, oleic acid; PA, phosphatidic acid; PAP, phosphatidate phosphatase; PIAA, phosphatidylinositol with arachidonic acid; PIOA, phosphatidylinositol with oleic acid; PIS, PI synthase; PLA2, phospholipase A2; PLC, phospholipase C; SCAP, SREBP cleavage–activating protein; SREBP-1c, sterol regulatory element–binding protein-1c; TG, triglyceride.