Acute effects of ethanol on feeding behavior and leptin-induced STAT3 phosphorylation in rat hypothalamus.
OBJECTIVE
Drinking ethanol stimulates the appetite, producing a positive energy balance. The mechanism by which ethanol regulates the appetite in the central nervous system, however, has not been fully understood. The aim of this study is to investigate the interaction of ethanol with the satiety effect of leptin, a hormone which suppresses the appetite in the hypothalamic region.


METHODS
: Leptin (7.5 micro g) or the same dose of phosphate buffer saline (PBS) was administered into the third ventricle (i.c.v.), 30 min after an intraperitoneal injection (i.p.) of ethanol (0.5 g/kg body weight) or the same dose of PBS.


METHODS
Adult male Sprague-Dawley rats weighing 290-320 g were used.


METHODS
Food intake was measured 2, 12 and 24 h after leptin i.c.v. infusion. The tyrosine phosphorylation of signal transducer and activator transcription factor 3 (STAT3) in the hypothalamus was analyzed by Western blotting.


RESULTS
The cumulative food intakes in the saline/leptin group (saline i.p.+leptin i.c.v.) were markedly reduced to about 45% of the saline/PBS group (saline i.p.+PBS i.c.v.) at 2, 12 and 24 h time points (P<0.05, 0.001, and 0.005, respectively). As compared with the saline/leptin group, those of the ethanol/leptin group (ethanol i.p.+leptin i.c.v.) were significantly increased to the level seen in the saline/PBS group at 12 and 24 h time points (P<0.05, and P<0.005 vs the saline/leptin group, respectively). Ethanol administration resulted in about a 50% reduction of the leptin-induced STAT3 tyrosine phosphorylation seen in the hypothalamic protein as compared to that of the saline/leptin group.


CONCLUSIONS
These findings suggest that ethanol-induced enhancement of the appetite may, in part, result from leptin resistance transiently caused by ethanol to attenuate the leptin signal transduction.
Fujita
N
N
The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Sakamaki
H
H
Uotani
S
S
Takahashi
R
R
Kuwahara
H
H
Kita
A
A
Oshima
K
K
Yamasaki
H
H
Yamaguchi
Y
Y
Eguchi
K
K
D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D007031:Hypothalamus / Q000378:metabolism*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*
D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; D020738:Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators; D000431:Ethanol