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Neurexin-3 in the paraventricular nucleus of the hypothalamus regulates body weight and glucose homeostasis independently of food intake.
Mu, Mingdao; Sun, Haoyu; Geng, Shuyan; Xu, Tianxiang; Sun, Chuanyao; Zhang, Zixu; Meng, Sibie; Li, Moyi; Liu, An; Yang, Zhiyuan; Xie, Wei.
Afiliación
  • Mu M; School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, P. R. China. mumingdao@qq.com.
  • Sun H; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China. mumingdao@qq.com.
  • Geng S; School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, P. R. China.
  • Xu T; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
  • Sun C; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
  • Zhang Z; School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, P. R. China.
  • Meng S; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
  • Li M; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
  • Liu A; School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, P. R. China.
  • Yang Z; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
  • Xie W; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, P. R. China.
Mol Brain ; 17(1): 49, 2024 Aug 01.
Article en En | MEDLINE | ID: mdl-39090731
ABSTRACT
Neurexin-3 (Nrxn3) has been genetically associated with obesity, but the underlying neural mechanisms remain poorly understood. This study aimed to investigate the role of Nrxn3 in the paraventricular nucleus of the hypothalamus (PVN) in regulating energy balance and glucose homeostasis. We found that Nrxn3 expression in the PVN was upregulated in response to metabolic stressors, including cold exposure and fasting. Using Cre-loxP technology, we selectively ablated Nrxn3 in CaMKIIα-expressing neurons of the PVN in male mice. This genetic manipulation resulted in marked weight gain attributable to increased adiposity and impaired glucose tolerance, without affecting food intake. Our findings identify PVN CaMKIIα-expressing neurons as a critical locus where Nrxn3 modulates energy balance by regulating adipogenesis and glucose metabolism, independently of appetite. These results reveal a novel neural mechanism potentially linking Nrxn3 dysfunction to obesity pathogenesis, suggesting that targeting PVN Nrxn3-dependent neural pathways may inform new therapeutic approaches for obesity prevention and treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Hipotalámico Paraventricular / Peso Corporal / Ingestión de Alimentos / Glucosa / Homeostasis / Proteínas del Tejido Nervioso Límite: Animals Idioma: En Revista: Mol Brain Asunto de la revista: BIOLOGIA MOLECULAR / CEREBRO Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Núcleo Hipotalámico Paraventricular / Peso Corporal / Ingestión de Alimentos / Glucosa / Homeostasis / Proteínas del Tejido Nervioso Límite: Animals Idioma: En Revista: Mol Brain Asunto de la revista: BIOLOGIA MOLECULAR / CEREBRO Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido