Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice.
We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 microg/kg) and sulfated CCK-8 (3.5 microg/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0. 3-fold respectively). Injections of leptin-CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin-CCK to regulate food intake.
Wang
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L
CURE/Digestive Diseases Research Center, West Los Angeles VA Medical Center, Department of Medicine and Brain Research Institute, University of California, Los Angeles, CA 90073, USA.
Martínez
V
V
Barrachina
M D
MD
Taché
Y
Y
D000273:Adipose Tissue; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002766:Cholecystokinin / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D020738:Leptin; D008032:Limbic System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011506:Proteins / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D011994:Recombinant Proteins / Q000494:pharmacology; D012249:Rhombencephalon / Q000187:drug effects
D020738:Leptin; D009419:Nerve Tissue Proteins; D011506:Proteins; D016760:Proto-Oncogene Proteins c-fos; D011994:Recombinant Proteins; D002766:Cholecystokinin