Prostaglandin mediates endotoxaemia-induced hypophagia by activation of pro-opiomelanocortin and corticotrophin-releasing factor neurons in rats

Exp Physiol. 2009 Mar;94(3):371-9. doi: 10.1113/expphysiol.2008.045435. Epub 2008 Dec 12.


Corticotrophin-releasing factor (CRF) and alpha-melanocyte-stimulating hormone (alpha-MSH), both of which are synthesized by hypothalamic neurons, play an essential role in the control of energy homeostasis. Neuroendocrine and behavioural responses induced by lipopolyssacharide (LPS) have been shown to involve prostaglandin-mediated pathways. This study investigated the effects of prostaglandin on CRF and alpha-MSH neuronal activities in LPS-induced anorexia. Male Wistar rats were pretreated with indomethacin (10 mg kg(-1); i.p.) or vehicle; 15 min later they received LPS (500 microg kg(-1); i.p.) or saline injection. Food intake, hormone responses and Fos-CRF and Fos-alpha-MSH immunoreactivity in the paraventricular and arcuate nuclei, respectively, were evaluated. In comparison with saline treatment, LPS administration induced lower food intake and increased plasma ACTH and corticosterone levels, as well as an increase in Fos-CRF and Fos-alpha-MSH double-labelled neurons in vehicle-pretreated rats. In contrast, indomethacin treatment partly reversed the hypophagic effect, blunted the hormonal increase and blocked the Fos-CRF and Fos-alpha-MSH hypothalamic double labelling increase in response to the LPS stimulus. These data demonstrate that the activation of pro-opiomelanocortin and CRF hypothalamic neurons following LPS administration is at least partly mediated by the prostaglandin pathway and is likely to be involved in the modulation of feeding behaviour during endotoxaemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Animals
  • Anorexia / chemically induced
  • Anorexia / metabolism
  • Anorexia / physiopathology
  • Appetite Regulation / drug effects
  • Appetite Regulation / physiology*
  • Corticosterone / metabolism
  • Corticotropin-Releasing Hormone / metabolism*
  • Cyclooxygenase Inhibitors / pharmacology
  • Disease Models, Animal
  • Endotoxemia / metabolism*
  • Hypothalamus / metabolism*
  • Indomethacin / pharmacology
  • Lipopolysaccharides
  • Male
  • Neurons / metabolism*
  • Pro-Opiomelanocortin / metabolism*
  • Prostaglandins / metabolism*
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Wistar
  • alpha-MSH / metabolism


  • Cyclooxygenase Inhibitors
  • Lipopolysaccharides
  • Prostaglandins
  • Proto-Oncogene Proteins c-fos
  • alpha-MSH
  • Pro-Opiomelanocortin
  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone
  • Indomethacin