A new look on brain mechanisms of acute illness anorexia.
Bacterial lipopolysaccharide (LPS) and other microbial substances trigger the organism's acute phase response and cause acute illness anorexia. Pro-inflammatory cytokines are major endogenous mediators of acute illness anorexia, but how LPS or cytokines stimulate the brain to inhibit eating is not fully resolved. One emerging mechanism involves the activation of the enzyme cyclooxygenase-2 (COX-2) in blood-brain barrier endothelial cells and the subsequent release of prostaglandin E2 (PGE2). Serotonin neurons in the midbrain raphe are targets of PGE2, and serotonergic projections from the midbrain raphe to the hypothalamus appear to be crucial for LPS anorexia. That is, raphe projections activate (1) the corticotrophin-releasing hormone neurons in the paraventricular nucleus which then elicit the stress response and (2) the pro-opiomelanocortin neurons in the arcuate nucleus which then release alphaMSH and elicit anorexia. Here we review available data to support a role for this brain mechanism in acute illness anorexia by center staging PGE2 signaling pathways that converge on central neural circuits that control normal eating. In addition, we review interactions between gonadal hormones and immune function that lead to sex differences in acute illness anorexia. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
Asarian
Lori
L
Institute of Food, Nutrition and Health, ETH Zurich, 8603, Schwerzenbach, Switzerland.
Langhans
Wolfgang
W
D000208:Acute Disease; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000473:pathology*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D008070:Lipopolysaccharides / Q000009:adverse effects; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics
D008070:Lipopolysaccharides; D012701:Serotonin; D051546:Cyclooxygenase 2; D015232:Dinoprostone