Inhibition of activation of ACCbeta, fatty acids synthase, might be a novel therapeutic strategy against diabetic nephropathy.

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461341
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: ISSHIKI KEIJI 滋賀医科大学, 医学部, 非常勤講師 (60378487)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 腎臓病学 / 糖尿病性腎症 / 脂肪毒性

Outline of Final Research Achievements

To investigate the role of ACCβ, fatty acids synthase, in initiation and progression of diabetic nephropathy, we examined the effect of ACCβ using streptozotocin-induced diabetic mouse model in podocyte-specific ACCβ overexpressing mice and proximal tubular cell-specific ACCβ overexpressing mice. Overexpression of ACCβ exacerbated podocyte injury and proximal tubular injury, respectively in streptozotocin-induced diabetic model. Furthermore, in ACCβ overexpressing-cultured podocytes and ACCβ overexpressing-cultured proximal tubular cells, podocyte injury and proximal tubular injury, respectively, were enhanced under high glucose condition. The AMPK activation by AICAR ameliorated both ACCβ-induced podocyte injury and ACCβ-induced proximal tubular injury under high glucose condition.
It is suggested that excess of ACCβ contributes to exacerbation of diabetic nephropathy, and the regulation of AMPK/ACCβ pathway may be a new therapeutic strategy to prevent diabetic nephropathy.

Free Research Field

腎臓病学