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Gap junctions regulate the activity of AgRP neurons and diet-induced obesity in male mice

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Autor(es):
de Souza, Gabriel O. ; Chaves, Fernanda M. ; Silva, Josiane N. ; Pedroso, Joao A. B. ; Metzger, Martin ; Frazao, Renata ; Donato Jr, Jose
Número total de Autores: 7
Tipo de documento: Artigo Científico
Fonte: Journal of Endocrinology; v. 255, n. 2, p. 16-pg., 2022-11-01.
Resumo

Recent studies indicated an important role of connexins, gap junction proteins, in the regulation of metabolism. However, most of these studies focused on the glial expression of connexins, whereas the actions of connexins in neurons are still poorly investigated. Thus, the present study had the objective to investigate the possible involvement of gap junctions, and in particular connexin 43 (CX43), for the central regulation of energy homeostasis. Initially, we demonstrated that hypothalamic CX43 expression was suppressed in fasted mice. Using whole-cell patch-clamp recordings, we showed that pharmacological blockade of gap junctions induced hyperpolarization and decreased the frequency of action potentials in 50-70% of agouti-related protein (AgRP)-expressing neurons, depending on the blocker used (carbenoxolone disodium, TAT-Gap19 or Gap 26). When recordings were performed with a biocytin-filled pipette, this intercellular tracer was detected in surrounding cells. Then, an AgRP-specific CX43 knockout (AgRP & UDelta;CX43) mouse was generated. AgRP & UDelta;CX43 mice exhibited no differences in body weight, adiposity, food intake, energy expenditure and glucose homeostasis. Metabolic responses to 24 h fasting or during refeeding were also not altered in AgRP & UDelta;CX43 mice. However, AgRP & UDelta;CX43 male, but not female mice, exhibited a partial protection against high-fat diet-induced obesity, even though no significant changes in energy intake or expenditure were detected. In summary, our findings indicate that gap junctions regulate the activity of AgRP neurons, and AgRP-specific CX43 ablation is sufficient to mildly prevent diet-induced obesity specifically in males. (AU)

Processo FAPESP: 21/11551-4 - Estudo dos circuitos hipotalâmicos que regulam o metabolismo e o sistema endócrino
Beneficiário:Josiane do Nascimento Silva
Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 19/21707-1 - Influência da privação alimentar na excitabilidade de neurônios que expressam o gene Kiss1
Beneficiário:Renata Frazão
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 17/21854-9 - Estudo dos efeitos de citocinas pró- e anti-inflamatórias sobre propriedades biofísicas de neurônios POMC e AgRP do núcleo arqueado do hipotálamo
Beneficiário:Fernanda Machado Chaves
Modalidade de apoio: Bolsas no Brasil - Doutorado
Processo FAPESP: 20/01318-8 - Sistema nervoso central como um alvo do hormônio do crescimento para a regulação de múltiplas funções biológicas
Beneficiário:Jose Donato Junior
Modalidade de apoio: Auxílio à Pesquisa - Temático
Processo FAPESP: 17/16473-6 - Processamento de estímulos aversivos: circuitaria entre o núcleo tegmental laterodorsal, a habênula, e os núcleos dorsal e mediano da rafe
Beneficiário:Martin Andreas Metzger
Modalidade de apoio: Auxílio à Pesquisa - Regular