Activation of the sympathetic nervous system by galanin-like peptide--a possible link between leptin and metabolism.
The effects of leptin upon body weight (BW) cannot be explained by its anorectic actions alone. Part of the metabolic changes elicited by leptin includes sympathetic nervous system activation leading to increased energy expenditure. Galanin-like peptide (GALP), a recently described hypothalamic neuropeptide, is up-regulated by leptin and has anorectic effects in the mouse. We postulated that GALP mediates effects of leptin upon metabolism. To test this hypothesis, we administered GALP centrally to the leptin-deficient ob/ob mouse. Acutely, GALP induced a decrease in food intake and BW, both of which remained significant relative to controls for 4 d. Chronic GALP administration resulted in a sustained decrease in BW and an increase in core body temperature, despite significant recovery of food intake. In a pair-fed model, chronic GALP treatment resulted in a greater decrease in BW than that seen in controls. Furthermore, GALP treatment resulted in increased body temperature and uncoupling protein 1 mRNA and protein in brown adipose tissue compared with controls. The expression of pro-opiomelanocortin (POMC) mRNA in the arcuate nucleus was decreased after chronic GALP treatment. These observations suggest that leptin's activation of the sympathetic nervous system, and ultimately thermogenesis, may be partially mediated by GALP through a melanocortin-independent mechanism.
Hansen
Karl R
KR
Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington 98195, USA.
Krasnow
Stephanie M
SM
Nolan
Michael A
MA
Fraley
Gregory S
GS
Baumgartner
James W
JW
Clifton
Donald K
DK
Steiner
Robert A
RA
D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D044089:Galanin-Like Peptide / Q000008:administration & dosage*; D007276:Injections, Intraventricular; D007473:Ion Channels; D020738:Leptin / Q000172:deficiency / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008660:Metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology*; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D044089:Galanin-Like Peptide; D007473:Ion Channels; D020738:Leptin; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; C000604372:Ucp1 protein, mouse; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; D011333:Pro-Opiomelanocortin