Abstract: SA-PO1038

WNK4 Deletion Inhibits Adipogenesis In Vitro and In Vivo

Session Information

  • Na+, K+, Cl-
    November 04, 2017 | Location: Hall H, Morial Convention Center
    Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

  • 703 Na+, K+, Cl- Basic

Authors

  • Takahashi, Daiei, Tokyo Medical and Dental University, Tokyo, Japan
  • Rai, Tatemitsu, TOKYO MEDICAL & DENTAL UNIV, TOKYO, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
  • Tanaka, Miyako, Nagoya University, Nagoya, Japan
  • Inoue, Yuichi, Tokyo medical and dental university, Tokyo, Japan
  • Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Chiga, Motoko, Department of Nephrology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Zeniya, Moko, Tokyo Medical and Dental University, Tokyo, Japan
  • Suganami, Takayoshi, Nagoya University, Nagoya, Japan
Background

The with-no-lysine kinase (WNK) 1 and WNK4 genes are responsible for pseudohypoaldosteronism type II (PHAII), a hereditary hypertensive disease. We have demonstrated the importance of the WNK4–OSR1/SPAK–NCC signaling cascade in the kidney for blood pressure regulation, however, the extrarenal roles of WNK4 is not clear. We previously presented WNK4 is induced in the early phase of 3T3-L1 adipocyte differentiation and is expressed in mouse mature adipose tissues. In this study, we evaluated WNK4’s contribution to the adipogenesis in vitro and in vivo.

Methods

We used mouse primary preadipocytes, 3T3-L1 fibroblasts, and human mesenchymal stem cells (hMSC-AT) to elucidate potential roles of WNK4 in adipose tissue. The functions of WNK4 in these cells was examined by siRNA specific to WNK4 (si-WNK4). We also generated WNK4 knock-down 3T3-L1 cell lines using TALEN. We fed WNK4-/- mice a high-fat diet and examined their metabolic functions.

Results

In mouse primary preadipocytes, WNK4 was predominantly expressed in the mature adipocyte, and WNK4 in the stromal vascular fraction was induced by the differentiation stimuli. WNK4 expression preceded the expression of key transcriptional factors PPARγ and C/EBPα. Si-WNK4-transfected 3T3-L1 cells and hMSC-AT cells showed reduced expression of PPARγ and C/EBPα and decreased lipid accumulation. WNK4 knocked-down 3T3-L1 cells also showed 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.

Conclusion

WNK4 is a key molecule of adipocyte differentiation and is involved in diet-induced adiposity. Thus, WNK4 would be a novel target molecule for the treatment of metabolic syndrome.

Funding

  • Government Support - Non-U.S.