Investigation of WNK4's function as a novel adipogenic factor

• 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
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: WNK4 / メタボリックシンドローム / 高血圧 / 肥満 / 脂肪細胞分化 / 医学 / 腎臓病学

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.

Research Products

• [Journal Article] WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice. (2017)
  • Author(s): Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, Nomura N, Zeniya M, Ochi H, Takeda S, Suganami T, Rai T, Uchida S.
  • Journal Title: EBioMedicine Volume: 18 Pages: 118-27
  • DOI: 10.1016/j.ebiom.2017.03.011
  • Peer Reviewed / Open Access
• [Presentation] WNK4 regulates adipocyte differentiation in 3T3-L1 cells (2016)
  • Author(s): Daiei Takahashi, Takayasu Mori, Eisei Sohara, Motoko Chiga, Yuichi Inoue, Naohiro Nomura, Moko Zeniya, Tatemitsu Rai, and Shinichi Uchida
  • Organizer: Annual Meeting of American Society of Nephrology
  • Place of Presentation: Chicago（米国）
  • Year and Date: 2016-11-19
  • Int'l Joint Research