PDF(Pubmed)
Abstract：
The coordination of food intake, energy storage, and expenditure involves complex interactions between hypothalamic neurons and peripheral tissues including pancreatic islets, adipocytes, muscle, and liver. Previous research shows that deficiency of the transcription factor Alx3 alters pancreatic islet-dependent glucose homeostasis. In this study we carried out a comprehensive assessment of metabolic alterations in Alx3 deficiency. We report that Alx3-deficient mice exhibit decreased food intake without changes in body weight, along with reduced energy expenditure and altered respiratory exchange ratio. Magnetic resonance imaging reveals increased adiposity and decreased muscle mass, which was associated with markers of motor and sympathetic denervation. By contrast, Alx3-deficient mice on a high-fat diet show attenuated weight gain and improved insulin sensitivity, compared to control mice. Gene expression analysis demonstrates altered lipogenic and lipolytic gene profiles. In wild type mice Alx3 is expressed in hypothalamic arcuate nucleus neurons, but not in major peripheral metabolic organs. Functional diffusion-weighted magnetic resonance imaging reveals selective hypothalamic responses to fasting in the arcuate nucleus of Alx3-deficient mice. Additionally, altered expression of proopiomelanocortin and melanocortin-3 receptor mRNA in the hypothalamus suggests impaired regulation of feeding behavior. This study highlights the crucial role for Alx3 in governing food intake, energy homeostasis, and metabolic nutrient partitioning, thereby influencing body mass composition.
摘要：
食物摄入的协调，储能，和支出涉及下丘脑神经元和包括胰岛在内的外周组织之间的复杂相互作用，脂肪细胞,肌肉，还有肝脏.先前的研究表明，转录因子Alx3的缺乏会改变胰岛依赖性葡萄糖稳态。在这项研究中，我们对Alx3缺乏症的代谢改变进行了全面评估。我们报告说，缺乏Alx3的小鼠表现出减少的食物摄入量，而体重没有变化，随着能量消耗的减少和呼吸交换率的改变。磁共振成像显示肥胖增加，肌肉质量减少，这与运动和交感神经支配的标志物有关。相比之下,高脂肪饮食中缺乏Alx3的小鼠表现出减轻的体重增加和改善的胰岛素敏感性，与对照小鼠相比。基因表达分析显示脂肪生成和脂肪分解基因谱改变。在野生型小鼠中，Alx3在下丘脑弓状核神经元中表达，但不是在主要的外周代谢器官。功能扩散加权磁共振成像揭示了Alx3缺陷小鼠弓状核对禁食的下丘脑反应。此外,下丘脑原黑皮质素和黑皮质素3受体mRNA表达的改变表明进食行为的调节受损。这项研究强调了Alx3在控制食物摄入方面的关键作用，能量稳态，和代谢营养分配，从而影响身体质量组成。
