Vagal afferents contribute to sympathoexcitation-driven metabolic dysfunctions

J Endocrinol. 2019 Mar 1;240(3):483-496. doi: 10.1530/JOE-18-0623.

Abstract

Multiple crosstalk between peripheral organs and the nervous system are required to maintain physiological and metabolic homeostasis. Using Vav3-deficient mice as a model for chronic sympathoexcitation-associated disorders, we report here that afferent fibers of the hepatic branch of the vagus nerve are needed for the development of the peripheral sympathoexcitation, tachycardia, tachypnea, insulin resistance, liver steatosis and adipose tissue thermogenesis present in those mice. This neuronal pathway contributes to proper activity of the rostral ventrolateral medulla, a sympathoregulatory brainstem center hyperactive in Vav3-/- mice. Vagal afferent inputs are also required for the development of additional pathophysiological conditions associated with deregulated rostral ventrolateral medulla activity. By contrast, they are dispensable for other peripheral sympathoexcitation-associated disorders sparing metabolic alterations in liver.

Keywords: GABAergic signals; adipose tissue; brainstem; diabetes; hypertension; liver; metabolic syndrome; sympathetic system; thermogenesis; ventrolateral medulla.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Afferent Pathways*
  • Animals
  • Brain Stem / metabolism
  • Brain Stem / physiopathology
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Medulla Oblongata / metabolism*
  • Medulla Oblongata / physiopathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proto-Oncogene Proteins c-vav / genetics
  • Proto-Oncogene Proteins c-vav / metabolism
  • Sympathetic Nervous System / metabolism
  • Sympathetic Nervous System / physiopathology*
  • Thermogenesis
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiopathology*

Substances

  • Proto-Oncogene Proteins c-vav
  • Vav2 protein, mouse
  • Vav3 protein, mouse