Enterostatin inhibition of dietary fat intake is modulated through the melanocortin system.
Enterostatin injected into the amygdala selectively reduces dietary fat intake by an action that involves a serotonergic component in the paraventricular nucleus. We have investigated the role of melanocortin signaling in the response to enterostatin by studies in melanocortin 4 receptor (MC4R) knock out mice and by the use of the MC4R and MC3R antagonist SHU9119, and by neurochemical phenotyping of enterostatin activated cells. We also determined the effect of enterostatin in vivo on the expression of AgRP in the hypothalamus and amygdala of rats and in culture on a GT1-7 neuronal cell line. Enterostatin had no effect on food intake in MC4R knock out mice. SHU9119 i.c.v. blocked the feeding response to amygdala enterostatin in rats. Amygdala enterostatin induced fos activation in alpha-melanocyte stimulating hormone (alpha-MSH) neurons in the arcuate nucleus. Enterostatin also reduced the expression of AgRP in the hypothalamus and amygdala and in GT1-7 cells. These data suggest enterostatin inhibits dietary fat intake through a melanocortin signaling pathway.
Lin
Ling
L
Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
Park
Miejung
M
York
David A
DA
D054369:Agouti-Related Protein; D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D002460:Cell Line; D003089:Colipases / Q000494:pharmacology*; D017931:DNA Primers / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D004792:Enzyme Precursors; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011498:Protein Precursors / Q000494:pharmacology*; D044104:Receptor, Melanocortin, Type 3 / Q000037:antagonists & inhibitors / Q000502:physiology; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D000521:alpha-MSH / Q000378:metabolism
D054369:Agouti-Related Protein; D003089:Colipases; D017931:DNA Primers; D004041:Dietary Fats; D004792:Enzyme Precursors; D036341:Intercellular Signaling Peptides and Proteins; C470053:Mc3r protein, mouse; D011498:Protein Precursors; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C103272:SHU 9119; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; C037107:procolipase; D009074:Melanocyte-Stimulating Hormones