Diabetes Metab J.  2011 Jun;35(3):219-225. 10.4093/dmj.2011.35.3.219.

ATP-Sensitive Potassium Channel-Deficient Mice Show Hyperphagia but Are Resistant to Obesity

• Park YB
• Choi YJ
• Park SY
• Kim JY
• Kim SH
• Song DK
• Won KC
• Kim YW

• KMID: 2175420
• DOI: http://doi.org/10.4093/dmj.2011.35.3.219

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.

Keyword

Appetite; Hypothalamus; Intra-abdominal fat; KATP channels

MeSH Terms

Animals
Appetite
Blood Glucose
Body Weight
Glucose
Hyperphagia
Hypothalamus
Intra-Abdominal Fat
KATP Channels
Mice
Neurons
Neuropeptide Y
Obesity
Potassium
Social Control, Formal
Blood Glucose
Glucose
KATP Channels
Neuropeptide Y
Potassium

Figure

• 

  Fig. 1 The serum glucose levels (A) and hypothalamic expressions of proopiomelanocortin (POMC; B) and neuropeptide Y (NPY; C) mRNA following intraperitoneal saline or glucose injection in overnight fasted C57BL/6 and Kir6.2 knockout (KO) mice. Values are the mean±standard error of 5 to 10 experimental animals per group. aP<0.05 vs. the saline group.

• 

  Fig. 2 The average daily caloric intake (A) and deposition of retroperitoneal white adipose tissue (RT-WAT; B) in control or high fat diet-fed C57BL/6 (normal) and Kir6.2-deficient (KO) mice. Values are the mean±standard error of 5 to 10 experimental animals per group. N-C, normal control group; N-HF, high fat-fed normal mice; KO-C, control diet fed Kir6.2 KO mice; KO-HF, high fat diet-fed Kir6.2 KO mice. aP<0.05 vs. N-C, bP<0.05 vs. KO-C.

• 

  Fig. 3 The serum levels of glucose (A), free fatty acids (FFA; B), insulin (C), and leptin (D), and the hypothalamic expressions of proopiomelanocortin (POMC; E) and neuropeptide Y (NPY; F) mRNA in control or high fat diet-fed C57BL/6 (normal) and Kir6.2-deficient (KO) mice. Values are the mean±standard error of 5 to 10 experimental animals per group. N-C, normal control group; N-HF, high fat-fed normal mice; KO-C, control diet-fed Kir6.2 KO mice; KO-HF, high fat diet-fed Kir6.2 KO mice. aP<0.05 vs. N-C.

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