Vagal sensory neuron-derived FGF3 controls insulin secretion

Area of Science:

• Neuroscience
• Metabolic Research
• Endocrinology

Background:

• Vagal nerve stimulation shows promise for chronic conditions, including metabolic disorders.
• The precise cellular and molecular mechanisms underlying vagal nerve stimulation's benefits are not fully understood.
• Understanding these pathways is crucial for optimizing therapeutic strategies.

Purpose of the Study:

• To investigate the molecular pathways involved in vagal nerve stimulation for metabolic disorders.
• To identify specific factors within the vagal nerve that influence metabolic regulation.
• To elucidate the role of fibroblast growth factor 3 (Fgf3) in vagal nerve-mediated metabolic control.

Main Methods:

• Measured Fgf3 mRNA levels in mouse vagal ganglia under metabolic stress.
• Utilized systemic and vagal sensory overexpression of Fgf3 in mouse models.
• Performed genetic ablation of Fgf3 in pancreatic vagal afferents.
• Investigated the effects of vagal afferent electrostimulation on glucose metabolism.

Main Results:

• Fgf3 mRNA was upregulated in vagal ganglia during acute metabolic stress.
• Fgf3 overexpression enhanced glucose-stimulated insulin secretion (GSIS), improved glucose tolerance, and increased energy expenditure.
• These effects were mediated by pancreas-projecting vagal sensory neurons.
• Fgf3 ablation in these neurons worsened diet-induced glucose intolerance.
• Vagal afferent stimulation improved GSIS and glucose clearance independently of efferent signals.

Conclusions:

• Vagal afferent signaling plays a direct role in regulating glucose-stimulated insulin secretion.
• Fibroblast growth factor 3 (Fgf3) is identified as a novel vagal sensory-derived factor.
• Fgf3 influences pancreatic beta-cell activity and overall metabolic homeostasis.