Investigation of WNK4's function as a novel adipogenic factor

2016 Fiscal Year Final Research Report

• Project/Area Number: 15H06184
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Takahashi Daiei 東京医科歯科大学, 医学部附属病院, 非常勤講師 (40759552)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Keywords: WNK4 / メタボリックシンドローム / 高血圧 / 肥満

Outline of Final Research Achievements

The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. However, WNKs' metabolic functions are not clear. In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adipocytes. In mouse primary preadipocytes and in 3T3-L1 adipocytes, WNK4 was markedly induced in the early phase of adipocyte differentiation. WNK4 expression preceded the expression of key transcriptional factors PPARγ and C/EBPα. WNK4-siRNA-transfected 3T3-L1 cells and human mesenchymal stem cells showed reduced expression of PPARγ and C/EBPα and lipid accumulation. WNK4 protein affected the DNA-binding ability of C/EBPβ and thereby reduced PPARγ expression. In the WNK4-/- mice, PPARγ and C/EBPα expression were decreased in adipose tissues, and the mice exhibited partial resistance to high-fat diet-induced adiposity. These data suggest that WNK4 may be a proadipogenic factor, and offer insights into the relationship between WNKs and energy metabolism.

Free Research Field

腎臓内科学