Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, 08195 Sant Cugat del Vallès, Spain.
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
Int J Mol Sci. 2021 Jun 8;22(12):6186. doi: 10.3390/ijms22126186.
Despite the substantial role played by the hypothalamus in the regulation of energy balance and glucose homeostasis, the exact mechanisms and neuronal circuits underlying this regulation remain poorly understood. In the last 15 years, investigations using transgenic models, optogenetic, and chemogenetic approaches have revealed that SF1 neurons in the ventromedial hypothalamus are a specific lead in the brain's ability to sense glucose levels and conduct insulin and leptin signaling in energy expenditure and glucose homeostasis, with minor feeding control. Deletion of hormonal receptors, nutritional sensors, or synaptic receptors in SF1 neurons triggers metabolic alterations mostly appreciated under high-fat feeding, indicating that SF1 neurons are particularly important for metabolic adaptation in the early stages of obesity. Although these studies have provided exciting insight into the implications of hypothalamic SF1 neurons on whole-body energy homeostasis, new questions have arisen from these results. Particularly, the existence of neuronal sub-populations of SF1 neurons and the intricate neurocircuitry linking these neurons with other nuclei and with the periphery. In this review, we address the most relevant studies carried out in SF1 neurons to date, to provide a global view of the central role played by these neurons in the pathogenesis of obesity and diabetes.
尽管下丘脑在调节能量平衡和葡萄糖稳态方面起着重要作用，但对于这种调节的具体机制和神经元回路仍知之甚少。在过去的 15 年中，使用转基因模型、光遗传学和化学遗传学方法的研究表明，腹内侧下丘脑的 SF1 神经元是大脑感知葡萄糖水平并在能量消耗和葡萄糖稳态中进行胰岛素和瘦素信号传导的特定关键，对进食的控制作用较小。在 SF1 神经元中删除激素受体、营养传感器或突触受体会引发代谢改变，这些改变在高脂肪喂养下更为明显，表明 SF1 神经元在肥胖早期的代谢适应中尤为重要。尽管这些研究为下丘脑 SF1 神经元对全身能量稳态的影响提供了令人兴奋的见解，但这些结果也提出了新的问题。特别是 SF1 神经元的神经元亚群的存在以及将这些神经元与其他核团和与外周联系起来的复杂神经回路。在这篇综述中，我们将讨论迄今为止在 SF1 神经元中进行的最相关研究，以提供这些神经元在肥胖和糖尿病发病机制中发挥核心作用的整体观点。
