GABA Type B Receptor Signaling in Proopiomelanocortin Neurons Protects Against Obesity, Insulin Resistance, and Hypothalamic Inflammation in Male Mice on a High-Fat Diet
| Autor: | Daisuke Hagiwara, Hidetaka Suga, Yutaka Oiso, Yoshihiro Ito, Yoshihisa Sugimura, Hiroshi Arima, Motomitsu Goto, Yoshiharu Ozawa, Shigeru Hagimoto, Koichi Adachi, Miyuki Shibata, Bernhard Bettler, Ryoichi Banno |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Pro-Opiomelanocortin Genotype Transcription Genetic medicine.medical_treatment GABAB receptor Biology Diet High-Fat Weight Gain Eating Mice 03 medical and health sciences Sex Factors 0302 clinical medicine Insulin resistance Proopiomelanocortin Internal medicine medicine Animals Obesity Receptor 030304 developmental biology Inflammation 0303 health sciences Interleukin-6 Tumor Necrosis Factor-alpha General Neuroscience Insulin digestive oral and skin physiology Insulin tolerance test Arcuate Nucleus of Hypothalamus Articles Neuropeptide Y receptor medicine.disease Endocrinology Receptors GABA-B nervous system Hypothalamus biology.protein Female Insulin Resistance Energy Metabolism Gene Deletion hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | 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 GABABreceptor-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 GABABreceptors 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 GABABreceptors is essential for proper energy balance. |
| Databáze: | OpenAIRE |
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