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 GABA B 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 TNF␣ 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 GABA B 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 GABA B receptors is essential for proper energy balance.

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The optimal timing for pulmonary valve replacement after Tetralogy of Fallot (TOF) repair remains controversial. In this study, we estimated the feasibility of using flow energy loss (FEL) to predict right ventricular (RV) deterioration due to pulmonary regurgitation after TOF repair. We examined RV outflow tract (RVOT) flow in nine patients who underwent TOF or double-outlet right ventricle repair in the intervention group (Group I) and compared them with three healthy children in the control group (Group C). We evaluated flow across the RVOT and pulmonary valve by vector flow mapping (VFM) on echocardiography and by phase contrast-magnetic resonance imaging (PC-MRI). Next, we calculated FEL and analyzed the relationship between FEL and clinical parameters of RV function. The mean FEL was significantly greater in Group I than in Group C (p = 0.002). Flow pattern and FEL were comparable by VFM and PC-MRI at the same phase 14.6 years after TOF repair. There was a significant positive correlation for the cardiothoracic ratio with both the mean FEL [correlation coefficient (r) = 0.78; p = 0.012] and the diastolic peak FEL (r = 0.75; p = 0.021) in Group I. There was also a significant positive correlation between the serial change in QRS duration with both the mean FEL (r = 0.82; p = 0.014) and the diastolic FEL (r = 0.70; p = 0.052) in Group I. FEL by VFM is an effective tool for evaluating ventricular deterioration caused by RV workload.