RT Journal Article
T1 Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.
A1 Ramírez, Sara
A1 Gómez-Valadés, Alicia G
A1 Schneeberger, Marc
A1 Varela, Luis
A1 Haddad-Tóvolli, Roberta
A1 Altirriba, Jordi
A1 Noguera, Eduard
A1 Drougard, Anne
A1 Flores-Martínez, Álvaro
A1 Imbernón, Mónica
A1 Chivite, Iñigo
A1 Pozo, Macarena
A1 Vidal-Itriago, Andrés
A1 Garcia, Ainhoa
A1 Cervantes, Sara
A1 Gasa, Rosa
A1 Nogueiras, Ruben
A1 Gama-Pérez, Pau
A1 Garcia-Roves, Pablo M
A1 Cano, David A
A1 Knauf, Claude
A1 Servitja, Joan-Marc
A1 Horvath, Tamas L
A1 Gomis, Ramon
A1 Zorzano, Antonio
A1 Claret, Marc
K1 MFN1
K1 OPA1
K1 POMC neurons
K1 ROS
K1 diabetes
K1 hypothalamus
K1 mitochondria
AB Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release.
YR 2017
FD 2017
LK http://hdl.handle.net/10668/11279
UL http://hdl.handle.net/10668/11279
LA en
DS RISalud
RD Apr 7, 2025