University of Bordeaux, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale, INSERM U1215, Bordeaux, France.
Neuronal Control of Metabolism (NeuCoMe) Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Nat Metab. 2021 Mar;3(3):299-308. doi: 10.1038/s42255-021-00345-3. Epub 2021 Feb 25.
Hypothalamic AgRP and POMC neurons are conventionally viewed as the yin and yang of the body's energy status, since they act in an opposite manner to modulate appetite and systemic energy metabolism. However, although AgRP neurons' functions are comparatively well understood, a unifying theory of how POMC neuronal cells operate has remained elusive, probably due to their high level of heterogeneity, which suggests that their physiological roles might be more complex than initially thought. In this Perspective, we propose a conceptual framework that integrates POMC neuronal heterogeneity with appetite regulation, whole-body metabolic physiology and the development of obesity. We highlight emerging evidence indicating that POMC neurons respond to distinct combinations of interoceptive signals and food-related cues to fine-tune divergent metabolic pathways and behaviours necessary for survival. The new framework we propose reflects the high degree of developmental plasticity of this neuronal population and may enable progress towards understanding of both the aetiology and treatment of metabolic disorders.
下丘脑的 AgRP 和 POMC 神经元通常被视为机体能量状态的阴阳两面，因为它们以相反的方式作用，调节食欲和全身能量代谢。然而，尽管 AgRP 神经元的功能得到了比较好的理解，但对于 POMC 神经元细胞如何运作的统一理论仍然难以捉摸，这可能是由于其高度的异质性，这表明它们的生理作用可能比最初想象的更复杂。在这篇观点文章中，我们提出了一个概念框架，将 POMC 神经元的异质性与食欲调节、全身代谢生理学和肥胖的发展联系起来。我们强调了一些新的证据，表明 POMC 神经元对不同的内感受信号和与食物相关的线索做出反应，以微调生存所需的不同代谢途径和行为。我们提出的新框架反映了该神经元群体高度的发育可塑性，这可能有助于我们理解代谢紊乱的病因和治疗方法。
