Role of fatty acid elongase Elovl6 in the sucrose preference formation

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In this study, we investigated the effects of Elovl6 deletion in leptin receptor-deficient db/db mice, a model of type 2 diabetes. We analyzed the body weights, serum glucose, insulin and HbA1c levels of db+/m, db/db, and db/db-Elovl6KO mice. We also performed immunohistochemical staining and quantitative RT-PCR analysis of islet.Although the obesity of db/db-Elovl6KO mice was similar to db/db mice, development of hyperglycemia and glucose intolerance was dramatically improved. Histological examination indicated that Elovl6 deletion was associated with increased islet mass in db/db mice, and this correlated with serum hyperinsulinemia and glucose-responsive insulin secretion. The expression of several inflammatory genes such as TNF-α and MCP-1 were reduced, and the expression of genes related to β cell function such as PDX-1 and insulin were increased in islets from db/db-Elovl6KO mice compared with db/dbmice. These results suggest that Elovl6 is an important factor on both beta-cell mass and function in T2D. Elovl6 inhibition can be a novel therapeutic target for T2D.