Arcuate nucleus proopiomelanocortin neurons mediate the acute anorectic actions of leukemia inhibitory factor via gp130.
The proinflammatory cytokine leukemia inhibitory factor (LIF) is induced in disease states and is known to inhibit food intake when administered centrally. However, the neural pathways underlying this effect are not well understood. We demonstrate that LIF acutely inhibits food intake by directly activating pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. We show that arcuate POMC neurons express the LIF-R, and that LIF stimulates the release of the anorexigenic peptide, alpha-MSH from ex vivo hypothalami. Transgenic mice lacking gp130, the signal transducing subunit of the LIF-R complex, specifically in POMC neurons fail to respond to LIF. Furthermore, LIF does not stimulate the release of alpha-MSH from the transgenic hypothalamic explants. These findings indicate that POMC neurons mediate the acute anorectic actions of central LIF administration and provide a mechanistic link between inflammation and food intake.
Grossberg
Aaron J
AJ
Department of Pediatrics, Oregon Health and Science University, Mail Code L-481, Portland, Oregon 97239, USA.
Scarlett
Jarrad M
JM
Zhu
XinXia
X
Bowe
Darren D
DD
Batra
Ayesha K
AK
Braun
Theodore P
TP
Marks
Daniel L
DL
D000818:Animals; D000855:Anorexia / Q000235:genetics / Q000503:physiopathology*; D001111:Arcuate Nucleus of Hypothalamus / Q000502:physiology*; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D050822:Cytokine Receptor gp130 / Q000502:physiology*; D017930:Genes, Reporter; D005838:Genotype; D053583:Interleukin-1beta / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011333:Pro-Opiomelanocortin / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000521:alpha-MSH / Q000502:physiology
D020934:Ciliary Neurotrophic Factor; D053583:Interleukin-1beta; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D050822:Cytokine Receptor gp130; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin