ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity.
10.4093/dmj.2011.35.3.219
- Author:
Yeul Bum PARK
1
;
Yun Jung CHOI
;
So Young PARK
;
Jong Yeon KIM
;
Seong Ho KIM
;
Dae Kyu SONG
;
Kyu Chang WON
;
Yong Woon KIM
Author Information
1. Department of Neurosurgery, Yeungnam University College of Medicine, Daegu, Korea. ywkim@med.yu.ac.kr
- Publication Type:Original Article
- Keywords:
Appetite;
Hypothalamus;
Intra-abdominal fat;
KATP channels
- MeSH:
Animals;
Appetite;
Blood Glucose;
Body Weight;
Glucose;
Hyperphagia;
Hypothalamus;
Intra-Abdominal Fat;
KATP Channels;
Mice;
Neurons;
Neuropeptide Y;
Obesity;
Potassium;
Social Control, Formal
- From:Diabetes & Metabolism Journal
2011;35(3):219-225
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (KATP) channels in the hypothalamic neurons. We hypothesized that a lack of glucose sensing in the hypothalamus affects the regulations of appetite and body weight. METHODS: To evaluate this hypothesis, the responses to glucose loading and high fat feeding for eight weeks were compared in Kir6.2 knock-out (KO) mice and control C57BL/6 mice, because Kir6.2 is a key component of the KATP channel. RESULTS: The hypothalamic neuropeptide Y (NPY) analyzed one hour after glucose injection was suppressed in C57BL/6 mice, but not in Kir6.2 KO mice, suggesting a blunted hypothalamic response to glucose in Kir6.2 KO mice. The hypothalamic NPY expression at a fed state was elevated in Kir6.2 KO mice and was accompanied with hyperphagia. However, the retroperitoneal fat mass was markedly decreased in Kir6.2 KO mice compared to that in C57BL/6 mice. Moreover, the body weight and visceral fat following eight weeks of high fat feeding in Kir6.2 KO mice were not significantly different from those in control diet-fed Kir6.2 KO mice, while body weight and visceral fat mass were elevated due to high fat feeding in C57BL/6 mice. CONCLUSION: These results suggested that Kir6.2 KO mice showed a blunted hypothalamic response to glucose loading and elevated hypothalamic NPY expression accompanied with hyperphagia, while visceral fat mass was decreased, suggesting resistance to diet-induced obesity. Further study is needed to explain this phenomenon.
