AI Article Synopsis
- The locus coeruleus (LC) contains VGlut2 neurons and plays a role in regulating body weight, but the role of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) and their connections to the LC remain poorly understood.
- Researchers used specific knockout techniques in chimeric mice and studied central nervous system projections to uncover the weight gain effects when MC4R was disabled in VGlut2 neurons.
- The study found that the PVN-LC connection and its excitatory pathways are crucial for weight management, suggesting that targeting these neural circuits may have potential in obesity treatments.
Article Abstract
The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVN and LC regulation of body weight, and axonal projections of LC neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LC circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LC neurons. The PVN → LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.
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| http://dx.doi.org/10.1096/fj.202201786R | DOI Listing |
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