New molecular techniques for exploring neuronal appetite pathways


Satiety and hunger are controlled by a complex and distributed neural network. The ‘standard model’ of energy homeostasis as the net product of orexigenic agouti-related protein and anorexigenic pro-opiomelanocortin neurons within the hypothalamus is the cornerstone of our understanding. It is, however, patently incomplete, and fundamental gaps exist in our understanding of the identity and organisation of cell types forming the appetitive neurocircuitry, their functions and the relevance of those identified and characterised in mice to the equivalent human neurocircuitry. Technological advances in single-cell and spatial transcriptomics, increasingly refined genetic tools for neuronal manipulation in mice, and the development of human hypothalamic cell models provide tools capable of addressing these fundamental questions and offer hope of one day approaching a ‘grand unifying theory’ of energy homeostasis.