Chronic exposure to low dose bacterial lipopolysaccharide inhibits leptin signaling in vagal afferent neurons

Physiol Behav. 2015 Feb;139:188-94. doi: 10.1016/j.physbeh.2014.10.032. Epub 2014 Nov 6.


Bacterially derived factors are implicated in the causation and persistence of obesity. Ingestion of a high fat diet in rodents and obesity in human subjects is associated with chronic elevation of low plasma levels of lipopolysaccharide (LPS), a breakdown product of Gram-negative bacteria. The terminals of vagal afferent neurons are positioned within the gut mucosa to convey information from the gut to the brain to regulate food intake and are responsive to LPS. We hypothesized that chronic elevation of LPS could alter vagal afferent signaling. We surgically implanted osmotic mini-pumps that delivered a constant, low-dose of LPS into the intraperitoneal cavity of rats (12.5 μg/kg/hr for 6 weeks). LPS-treated rats developed hyperphagia and showed marked changes in vagal afferent neuron function. Chronic LPS treatment reduced vagal afferent leptin signaling, characterized by a decrease in leptin-induced STAT3 phosphorylation. In addition, LPS treatment decreased cholecystokinin-induced satiety. There was no alteration in leptin signaling in the hypothalamus. These findings offer a mechanism by which a change in gut microflora can promote hyperphagia, possibly leading to obesity.

Keywords: Vagal afferent neurons; metabolic endotoxemia; suppressor of cytokine signaling 3; toll-like receptor 4.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blotting, Western
  • Eating / physiology*
  • Hyperphagia / physiopathology
  • Immunohistochemistry
  • Leptin / metabolism*
  • Lipopolysaccharides / toxicity*
  • Male
  • Neurons, Afferent / physiology*
  • Nodose Ganglion / physiopathology*
  • Peroxidase / metabolism
  • Rats, Wistar
  • Satiation / physiology
  • Sincalide / administration & dosage
  • Sincalide / metabolism
  • Weight Gain / physiology


  • Leptin
  • Lipopolysaccharides
  • Peroxidase
  • Sincalide