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WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice
The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is clear. In this study, we found that WNK4 was expressed in mouse adipose tissue and 3T3-L1 adip...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405161/ https://www.ncbi.nlm.nih.gov/pubmed/28314693 http://dx.doi.org/10.1016/j.ebiom.2017.03.011 |
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author | Takahashi, Daiei Mori, Takayasu Sohara, Eisei Tanaka, Miyako Chiga, Motoko Inoue, Yuichi Nomura, Naohiro Zeniya, Moko Ochi, Hiroki Takeda, Shu Suganami, Takayoshi Rai, Tatemitsu Uchida, Shinichi |
author_facet | Takahashi, Daiei Mori, Takayasu Sohara, Eisei Tanaka, Miyako Chiga, Motoko Inoue, Yuichi Nomura, Naohiro Zeniya, Moko Ochi, Hiroki Takeda, Shu Suganami, Takayoshi Rai, Tatemitsu Uchida, Shinichi |
author_sort | Takahashi, Daiei |
collection | PubMed |
description | The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is 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. |
format | Online Article Text |
id | pubmed-5405161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-54051612017-05-05 WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice Takahashi, Daiei Mori, Takayasu Sohara, Eisei Tanaka, Miyako Chiga, Motoko Inoue, Yuichi Nomura, Naohiro Zeniya, Moko Ochi, Hiroki Takeda, Shu Suganami, Takayoshi Rai, Tatemitsu Uchida, Shinichi EBioMedicine Research Paper The with-no-lysine kinase (WNK) 4 gene is a causative gene in pseudohypoaldosteronism type II. Although WNKs are widely expressed in the body, neither their metabolic functions nor their extrarenal role is 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. Elsevier 2017-03-08 /pmc/articles/PMC5405161/ /pubmed/28314693 http://dx.doi.org/10.1016/j.ebiom.2017.03.011 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Takahashi, Daiei Mori, Takayasu Sohara, Eisei Tanaka, Miyako Chiga, Motoko Inoue, Yuichi Nomura, Naohiro Zeniya, Moko Ochi, Hiroki Takeda, Shu Suganami, Takayoshi Rai, Tatemitsu Uchida, Shinichi WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title | WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title_full | WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title_fullStr | WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title_full_unstemmed | WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title_short | WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice |
title_sort | wnk4 is an adipogenic factor and its deletion reduces diet-induced obesity in mice |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405161/ https://www.ncbi.nlm.nih.gov/pubmed/28314693 http://dx.doi.org/10.1016/j.ebiom.2017.03.011 |
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