Hyperphagia and obesity in Na,K-ATPase alpha2 subunit-defective mice.
OBJECTIVE
The Na,K-ATPase alpha2 subunit gene (Atp1a2) is expressed in the brain, skeletal muscles, heart, and adipocytes. Specific function of the alpha2 subunit, such as involvement in differentiation and function of adipocytes, has not been addressed. The aim of this study was to examine whether Atp1a2-defective heterozygous mice show obesity and reveal the mechanisms underlying the obesity.


METHODS
We measured the differentiation and glucose uptake function of in vitro-differentiated adipocytes derived from embryonic fibroblasts of Atp1a2-defective mice. Food intake, body temperature, metabolic rate, and spontaneous activity and mRNA levels of neuropeptide genes were compared between the heterozygous and wild-type adult mice.


RESULTS
Atp1a2 heterozygous female mice developed obesity after middle age. The time course of in vitro adipocyte differentiation of embryonic fibroblasts isolated from wild type, heterozygous, and homozygous mice was not different, glucose and Rb uptake activities of the in vitro-differentiated adipocytes were not altered, and the effects of insulin on glucose uptake and those of monensin and ouabain on Rb uptake were similar among the genotypes. However, food intake in the light phase was significantly greater in the heterozygous mice than the wild type in the 24-hour dark-light cycle, whereas it was similar under constant-light condition. Body temperature, metabolic rate at rest, and spontaneous motor activity of the heterozygous mice were similar to those of the wild type. Orexin mRNA level was lower in heterozygous than wild-type mice.


CONCLUSIONS
The Na,K-ATPase alpha2 subunit is not involved in the differentiation or in glucose and Rb uptake function of in vitro-differentiated adipocytes. Hyperphagia is the likely primary cause of obesity in Atp1a2 heterozygous mice.
Kawakami
Kiyoshi
K
Division of Biology, Center for Molecular Medicine, Jichi Medical School, Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498. Japan. kkawakam@jichi.ac.jp
Onaka
Tatsushi
T
Iwase
Michiko
M
Homma
Ikuo
I
Ikeda
Keiko
K
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017931:DNA Primers; D005247:Feeding Behavior; D005260:Female; D005947:Glucose / Q000378:metabolism; D006579:Heterozygote; D006963:Hyperphagia / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000235:genetics / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose