Conditional microglial depletion in rats leads to reversible anorexia and weight loss by disrupting gustatory circuitry

Brain Behav Immun. 2019 Mar;77:77-91. doi: 10.1016/j.bbi.2018.12.008. Epub 2018 Dec 19.


Microglia are highly sensitive to dietary influence, becoming activated acutely and long-term by high fat diet. However, their role in regulating satiety and feeding in healthy individuals remains unclear. Here we show that microglia are essential for the normal regulation of satiety and metabolism in rats. Short-term microglial depletion in a Cx3cr1-Dtr rat led to a dramatic weight loss that was largely accounted for by an acute reduction in food intake. This weight loss and anorexia were not likely due to a sickness response since the rats did not display peripheral or central inflammation, withdrawal, anxiety-like behavior, or nausea-associated pica. Hormonal and hypothalamic anatomical changes were largely compensatory to the suppressed food intake, which occurred in association with disruption of the gustatory circuitry at the paraventricular nucleus of the thalamus. Thus, microglia are important in supporting normal feeding behaviors and weight, and regulating preference for palatable food. Inhibiting this circuitry is able to over-ride strong compensatory drives to eat, providing a potential target for satiety control.

Keywords: Arcuate nucleus; Cx3cr1-Dtr rat; Energy expenditure; Ghrelin; Hypothalamus; Inflammation; Leptin; Microglia; Neuropeptide Y; Paraventricular thalamic nucleus; Satiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / metabolism
  • Appetite / physiology
  • Body Weight
  • Brain / metabolism
  • Diet
  • Disease Models, Animal
  • Eating / physiology
  • Energy Metabolism / physiology
  • Feeding Behavior / physiology*
  • Ghrelin / metabolism
  • Hypothalamus / metabolism
  • Male
  • Microglia / physiology*
  • Midline Thalamic Nuclei / metabolism
  • Midline Thalamic Nuclei / physiology
  • Neuropeptide Y / metabolism
  • Rats
  • Rats, Wistar
  • Satiety Response / physiology*
  • Weight Loss


  • Ghrelin
  • Neuropeptide Y