Attenuation of leptin-mediated effects by monosodium glutamate-induced arcuate nucleus damage.
Leptin is a protein secreted by adipocytes that is important in regulating appetite and adiposity. Recent studies have suggested the presence of leptin receptors in the arcuate nucleus of the hypothalamus (ANH). Neonatal administration of monosodium glutamate (MSG) damages the ANH, resulting in obesity and neuroendocrine dysfunction. Neonatal administration of MSG was utilized to test the hypothesis that the anatomic site for many of leptin's actions is the ANH. Female control (n = 6) and MSG-treated rats (n = 7) were implanted for 14 days with osmotic minipumps containing phosphate-buffered saline or leptin (1 mg.kg-1.day-1). Leptin suppressed (P < 0.05) body weight gain in controls but did not suppress weight gain in MSG-treated rats. Leptin decreased (P < 0.05) fat depots in controls but had no effect in MSG-treated rats. Night feeding was suppressed (P < 0.05) in leptin-treated control rats. MSG-treated rats showed a suppression in food intake that was of a smaller magnitude and appeared later in the course of leptin treatment. These findings suggest that leptin mediates some physiological actions related to fat mobilization via receptors located in the ANH.
Dawson
R
R
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610, USA.
Pelleymounter
M A
MA
Millard
W J
WJ
Liu
S
S
Eppler
B
B
D000273:Adipose Tissue / Q000187:drug effects* / Q000254:growth & development; D000818:Animals; D000831:Animals, Newborn; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects*; D002940:Circadian Rhythm; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007263:Infusions, Parenteral; D020738:Leptin; D009765:Obesity / Q000139:chemically induced / Q000503:physiopathology*; D011247:Pregnancy; D011506:Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012970:Sodium Glutamate / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D015430:Weight Gain / Q000187:drug effects
D020738:Leptin; D011506:Proteins; D012970:Sodium Glutamate