In 2024, new insights identified a cluster of leptin-targeted neurons and integrative networks that link sensory inputs (heat and food perception) with feeding centres and peripheral systems. Key findings revealed hypothalamic site-specific adaptive mechanisms, in which nutritional state-dependent remodelling of extracellular compounds and neuropeptide transmission calibrate appetite via the arcuate nucleus.
Key advances
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AKT-dependent hepatic phosphorylation of MFF Ser131 triggers transient mitochondrial fragmentation, which regulates glucose production via proopiomelanocortin neurons in response to food cues or refeeding2.
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Tanycytes serve as integrative cellular foci that link thermosensing and feeding centres in the arcuate nucleus to limit feeding, as part of the thermodefensive response during fever or disease-induced hyperthermia3.
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Fast-acting leptin-targeted neurons expressing BNC2 in the arcuate nucleus rapidly induce satiety, and act as precise counterparts to agouti-related protein (AgRP) neurons by directly inhibiting them via GABAA receptors6.
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A stochastic, state-dependent release of αMSH and NPY from the arcuate nucleus calibrates the rate of satiation by modulating PVHMC4R neuronal activity through competitive neuropeptide signalling that regulates intracellular levels of cAMP8.
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A pathological hypothalamic assembly between the perineural net and AgRP circuitry (neurofibrosis), compromises insulin penetration and signalling in the arcuate nucleus, which contributes to insulin resistance and obesity progression9.
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References
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Garcia-Caceres, C. Advances in appetite regulation by the arcuate nucleus. Nat Rev Endocrinol 21, 71–72 (2025). https://doi.org/10.1038/s41574-024-01079-4
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DOI: https://doi.org/10.1038/s41574-024-01079-4
