Arcuate AgRP, but not POMC neurons, modulate paraventricular CRF synthesis and release in response to fasting

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Alves Fernandes, Alan Carlos ; de Oliveira, Franciane Pereira ; Fernandez, Gimena ; Vieira, Luane da Guia ; Rosa, Cristiane Gugelmin ; do Nascimento, Tais ; Franca, Suzelei de Castro ; Donato Jr, Jose ; Vella, Kristen R. ; Antunes-Rodrigues, Jose ; Mecawi, Andre ; Perello, Mario ; Kagohara Elias, Lucila Leico ; Rorato, Rodrigo

• Tipo de documento: Artigo Científico
• Fonte: CELL AND BIOSCIENCE; v. 12, n. 1, p. 14-pg., 2022-07-28.

Resumo

Background The activation of the hypothalamic-pituitary-adrenal (HPA) axis is essential for metabolic adaptation in response to fasting. However, the neurocircuitry connecting changes in the peripheral energy stores to the activity of hypothalamic paraventricular corticotrophin-releasing factor (CRFPVN) neurons, the master controller of the HPA axis activity, is not completely understood. Our main goal was to determine if hypothalamic arcuate nucleus (ARC) POMC and AgRP neurons can communicate fasting-induced changes in peripheral energy stores, associated to a fall in plasma leptin levels, to CRFPVN neurons to modulate the HPA axis activity in mice. Results We observed increased plasma corticosterone levels associate with increased CRFPVN mRNA expression and increased CRFPVN neuronal activity in 36 h fasted mice. These responses were associated with a fall in plasma leptin levels and changes in the mRNA expression of Agrp and Pomc in the ARC. Fasting-induced decrease in plasma leptin partially modulated these responses through a change in the activity of ARC neurons. The chemogenetic activation of POMCARC by DREADDs did not affect fasting-induced activation of the HPA axis. DREADDs inhibition of AgRPARC neurons reduced the content of CRFPVN and increased its accumulation in the median eminence but had no effect on corticosterone secretion induced by fasting. Conclusion Our data indicate that AgRPARC neurons are part of the neurocircuitry involved in the coupling of PVNCRF activity to changes in peripheral energy stores induced by prolonged fasting. (AU)

• Processo FAPESP: 16/17968-6 - Circuitaria e fenótipos neuronais hipotalâmicos envolvidos no acoplamento da atividade do eixo hipotálamo-hipófise-adrenal às alterações da homeostase energética
• Beneficiário: Rodrigo César Rorato
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/27581-0 - Controle da secreção de vasopressina na gestação e suas implicações na fisiopatologia da Pré-Eclâmpsia
• Beneficiário: Andre de Souza Mecawi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores