Diabetes & Metabolism Journal

Original Article

ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity: Yeul Bum Park, Yun Jung Choi, So Young Park, Jong Yeon Kim, Seong Ho Kim, Dae Kyu Song, Kyu Chang Won, Yong Woon Kim; Diabetes Metab J. 2011;35(3):219-225. Published online June 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.3.219

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Background

The hypothalamus, the center for body weight regulation, can sense changes in blood glucose level based on ATP-sensitive potassium (K_ATP) 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 K_ATP 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.

Citations

Citations to this article as recorded by

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