Metabolic, gastrointestinal, and CNS neuropeptide effects of brain leptin administration in the rat.
To investigate whether brain leptin involves neuropeptidergic pathways influencing ingestion, metabolism, and gastrointestinal functioning, leptin (3.5 micrograms) was infused daily into the third cerebral ventricular of rats for 3 days. To distinguish between direct leptin effects and those secondary to leptin-induced anorexia, we studied vehicle-infused rats with food available ad libitum and those that were pair-fed to leptin-treated animals. Although body weight was comparably reduced (-8%) and plasma glycerol was comparably increased (142 and 17%, respectively) in leptin-treated and pair-fed animals relative to controls, increases in plasma fatty acids and ketones were only detected (132 and 234%, respectively) in pair-fed rats. Resting energy expenditure (-15%) and gastrointestinal fill (-50%) were reduced by pair-feeding relative to the ad libitum group, but they were not reduced by leptin treatment. Relative to controls, leptin increased hypothalamic mRNA for corticotropin-releasing hormone (CRH; 61%) and for proopiomelanocortin (POMC; 31%) but did not reduce mRNA for neuropeptide Y. These results suggest that CNS leptin prevents metabolic/gastrointestinal responses to caloric restriction by activating hypothalamic CRH- and POMC-containing pathways and raise the possibility that these peripheral responses to CNS leptin administration contribute to leptin's anorexigenic action.
van Dijk
G
G
Department of Animal Physiology, University of Groningen, 9750 AA Haren, The Netherlands. g.van.dijk@bio.rug.nl
Seeley
R J
RJ
Thiele
T E
TE
Friedman
M I
MI
Ji
H
H
Wilkinson
C W
CW
Burn
P
P
Campfield
L A
LA
Tenenbaum
R
R
Baskin
D G
DG
Woods
S C
SC
Schwartz
M W
MW
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001786:Blood Glucose; D001835:Body Weight / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005223:Fats / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006003:Glycogen / Q000097:blood; D006120:Grooming / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D017403:In Situ Hybridization; D007328:Insulin / Q000097:blood; D020738:Leptin; D008297:Male; D010084:Oxidation-Reduction; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020318:Rats, Long-Evans; D012146:Rest / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005223:Fats; D007328:Insulin; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D014280:Triglycerides; D011333:Pro-Opiomelanocortin; D006003:Glycogen; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone