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Leptin-mediated hypothalamic pathway of cholecystokinin (CCK-8) to regulate body weight in free-feeding rats.
- Source :
-
Endocrinology [Endocrinology] 2008 Apr; Vol. 149 (4), pp. 1994-2000. Date of Electronic Publication: 2007 Dec 20. - Publication Year :
- 2008
-
Abstract
- Regulation of body weight (BW) results from the interplay between different hormonal systems acting at central and peripheral level. This study aims at characterizing the involvement of cholecystokinin (CCK) in BW and energy balance regulation. We have characterized, in free-feeding rats, the effect of CCK-8 on 1) food intake, BW, and adiposity; 2) skeletal muscle metabolism; 3) leptin signaling pathway within the arcuate nucleus of the hypothalamus; and 4) the permeability of brain barriers to leptin. We demonstrate here that CCK-8 acutely decreases BW by a mechanism partially dependent on central leptin pathways, based on the following results: 1) the effect of CCK was less intense in rats lacking functional leptin receptors (Zucker fa/fa), 2) CCK-8 facilitated the uptake of leptin from peripheral circulation to cerebrospinal fluid (CSF), 3) the concentration of leptin in CSF of rats receiving CCK was more elevated in those animals showing higher loss of BW, and 4) CCK activated leptin signaling pathways within the hypothalamus as well as phosphorylation of AMP-activated protein kinase in skeletal muscle. We also suggest that gain of BW may be linked to individual susceptibility to the effect of CCK, because we observed that in animals treated with this hormone, the increase of BW negatively correlated with leptin concentration within the CSF. Our data show that CCK has a negative impact on energy balance and suggest that CCK facilitates the access of leptin to hypothalamic areas, thus allowing leptin to act on hypothalamic targets involved in BW control.
- Subjects :
- AMP-Activated Protein Kinases
Acetyl-CoA Carboxylase metabolism
Adipose Tissue drug effects
Adiposity
Animals
Eating drug effects
Leptin cerebrospinal fluid
Male
Multienzyme Complexes metabolism
Muscle, Skeletal enzymology
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-fos analysis
Rats
Rats, Sprague-Dawley
STAT3 Transcription Factor analysis
Body Weight drug effects
Hypothalamus physiology
Leptin physiology
Sincalide pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0013-7227
- Volume :
- 149
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Endocrinology
- Publication Type :
- Academic Journal
- Accession number :
- 18096657
- Full Text :
- https://doi.org/10.1210/en.2007-1286