PT  - JOURNAL ARTICLE
AU  - Yoshihiro Ito
AU  - Ryoichi Banno
AU  - Miyuki Shibata
AU  - Koichi Adachi
AU  - Shigeru Hagimoto
AU  - Daisuke Hagiwara
AU  - Yoshiharu Ozawa
AU  - Motomitsu Goto
AU  - Hidetaka Suga
AU  - Yoshihisa Sugimura
AU  - Bernhard Bettler
AU  - Yutaka Oiso
AU  - Hiroshi Arima
TI  - GABA Type B Receptor Signaling in Proopiomelanocortin Neurons Protects Against Obesity, Insulin Resistance, and Hypothalamic Inflammation in Male Mice on a High-Fat Diet
AID  - 10.1523/JNEUROSCI.0897-13.2013
DP  - 2013 Oct 23
TA  - The Journal of Neuroscience
PG  - 17166--17173
VI  - 33
IP  - 43
4099  - http://www.jneurosci.org/content/33/43/17166.short
4100  - http://www.jneurosci.org/content/33/43/17166.full
SO  - J. Neurosci.2013 Oct 23; 33
AB  - There is evidence suggesting that the GABA system in the arcuate nucleus, where orexigenic neuropeptide Y and agouti-related peptide as well as anorexigenic proopiomelanocortin (POMC) are expressed, plays an important role in energy balance. In this study, we generated POMC-specific GABAB receptor-deficient [knock-out (KO)] mice. Male KO mice on a high-fat diet (HFD) showed mild increases in body weight (BW) at the age of 9 weeks compared to wild-type (WT) mice, and the differences remained significant until 16 weeks old. However, there was no difference in BW in females between genotypes. While food intake was similar between genotypes, oxygen consumption was significantly decreased in the male KO mice. The insulin tolerance test revealed that the male KO mice were less insulin sensitive compared to WT mice at the age of 8 weeks, when there was no significant difference in BW between genotypes. Despite increased BW, POMC mRNA expression in the arcuate nucleus was significantly decreased in the KO mice compared to WT mice at the age of 16 weeks. Furthermore, the expression of TNFα as well as IL-6, proinflammatory markers in the hypothalamus, was significantly increased in the KO mice on a HFD compared to WT mice. This demonstrates that the deletion of GABAB receptors in POMC neurons in the male mice on a HFD results in obesity, insulin resistance, and hypothalamic inflammation. Furthermore, the decreased POMC expression in the obese KO mice suggests that the regulation of POMC expression through GABAB receptors is essential for proper energy balance.