Messenger RNA levels of enzymes involved in glycerolipid synthesis in the brain of the mouse and its alterations in Agpat2-/- and db/db mice.

Abstract

AimsExpression of genes encoding enzymes involved in glycerolipid and monoacylglycerol pathways in specific brain regions is poorly known and its impact in insulin resistance (IR) and type 2 diabetes (T2D) in the brain remains unreported. We determined mRNA levels of enzymes involved in glycerolipid synthesis in different regions of the mouse brain and evaluated their changes in two models of IR and T2D, the Agpat2-/- and Leprdb/db mice. MethodsCerebral cortex, hypothalamus, hippocampus and cerebellum were dissected from adult Agpat2-/- mice, Leprdb/db mice and their respective wild type littermates. Total RNA was isolated and mRNA abundance was measured by RT-qPCR. Key findingsGPAT1, AGPAT1-4, LIPIN1/2, DGAT1/2 and MOGAT1 mRNAs were detected in all studied brain regions, whereas GPAT2, LIPIN3 and MOGAT2 were undetectable. Abundance of AGPATs, LIPIN1 and DGAT1, was higher in cerebellum and hypothalamus. LIPIN2 and MOGAT1 levels were higher in hypothalamus, and DGAT2 was higher in cortex and hypothalamus. In Agpat2-/- mice, LIPIN1 levels were increased in all the brain regions. By contrast, GPAT1 in cortex and hypothalamus, AGPAT3 in hippocampus and hypothalamus, AGPAT4 in hypothalamus, and MOGAT1 in cortex, hypothalamus and cerebellum were lower in Agpat2-/- mice. Leprdb/db mice showed fewer and milder changes, with increased levels of GPAT1 and LIPIN1 in cerebellum, and AGPAT3 in hypothalamus. Conclusions and SignificanceEnzymes of glycerolipids synthesis are differentially expressed across regions of the mouse brain. Two mouse models of IR and T2D have altered gene expression of glycerolipid enzymes in the brain.