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Overexpression of WNK1 in POMC-expressing neurons reduces weigh gain via WNK4-mediated degradation of Kir6.2.

 Woo Young Chung  ;  Jung Woo Han  ;  Woon Heo  ;  Min Goo Lee  ;  Joo Young Kim 
 Molecular and Cellular Biochemistry, Vol.447(1~2) : 165-174, 2018 
Journal Title
 Molecular and Cellular Biochemistry 
Issue Date
Aging/genetics ; Aging/metabolism ; Animals ; Gene Expression Regulation* ; HEK293 Cells ; Humans ; Hypothalamus/cytology ; Hypothalamus/metabolism* ; KATP Channels/genetics ; KATP Channels/metabolism* ; Mice ; Mice, Transgenic ; Neurons/cytology ; Neurons/metabolism* ; Pro-Opiomelanocortin/biosynthesis* ; Pro-Opiomelanocortin/genetics ; Protein Stability ; Protein-Serine-Threonine Kinases/biosynthesis* ; Protein-Serine-Threonine Kinases/genetics ; Proteolysis* ; Rats ; WNK Lysine-Deficient Protein Kinase 1/biosynthesis* ; WNK Lysine-Deficient Protein Kinase 1/genetics
Appetite ; Kir6.2 ; POMC-expressing neuron ; Protein degradation ; Transgenic mice ; WNK1 ; WNK4
"With no lysine" (WNK) kinases have been shown to regulate various ion transporters in various tissues, but studies on the function of WNK kinases in the brain have been limited. In this study, we discovered that WNK1 and WNK4 in POMC-expressing neuronal cells in WNK1 overexpressed transgenic mice (WNK1 TG) decrease appetite via degradation of Kir6.2. Weight gain after 20 weeks of age was delayed in WNK1 TG mice as a result of reduced food intake. Expression of WNK1 and proopiomelanocortin (POMC) was higher in POMC-expressing neurons in the hypothalamus of WNK1 TG mice than in WT mice. Immunostaining of serial sections of the hypothalamus revealed that POMC-expressing neurons were smaller in WNK1 TG mice than in WT mice. In addition, expression of Kir6.2 was significantly reduced in WNK1 TG mice. Overexpression and knockdown of WNK4 demonstrated that WNK4 regulates protein expression of Kir6.2 via protein-protein interaction. Accordingly, reduced age-dependent weight gain of WNK1 TG mice seems to be related with the decreased Kir6.2 expression via WNK1- and WNK4-regulated protein stability of Kir6.2.
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1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Joo Young(김주영) ORCID logo https://orcid.org/0000-0003-2623-1491
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
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