Autor(es)

de Souza, Gabriel O. ; Chaves, Fernanda M. ; Silva, Josiane N. ; Pedroso, Joao A. B. ; Metzger, Martin ; Frazao, Renata ; Donato Jr, Jose

• 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