Chronic ethanol consumption increases plasma leptin levels and alters leptin receptors in the hypothalamus and the perigonadal fat of C57BL/6 mice.
BACKGROUND
Leptin, a protein secreted from adipocytes, and leptin receptors, expressed in the hypothalamus and fat tissue, regulate energy balance and adiposity. Leptin receptors exist as several forms that are delineated by the length of their cytoplasmic domains. Only the longest form is physiologically active through stimulation of the signal transducers and activators of transcription (STAT) second messenger system. Previous studies demonstrated that chronic ethanol consumption increases body adiposity and circulating leptin levels. This study examined the effect of chronic alcohol intake on the expression of leptin receptors and associated STAT second messengers in the hypothalamus and fat tissue.


METHODS
Female C57BL/6 mice were given water or 20% w/v ethanol and Purina 5001 laboratory chow ad libitum for 2 or 5 weeks. Plasma leptin levels were determined by radioimmunoassay and body adiposity was evaluated by measuring the amount of perigonadal fat. Expression of leptin receptors as well as STAT molecules in whole-cell lysates of the hypothalamus and the perigonadal fat were assayed by Western blot analysis.


RESULTS
Plasma leptin and perigonadal fat were increased after 5 weeks. The overall expression of leptin receptors was increased while the expression of the physiologically active long form of leptin receptor was decreased in the hypothalamus and the perigonadal fat of ethanol-consuming mice. Ethanol consumption also decreased hypothalamic expression of STAT3, a protein associated with leptin receptor activation in this region of the brain. In contrast, STAT1, a protein associated with leptin receptor activation in adipose tissue, was significantly elevated in the perigonadal fat of ethanol-consuming mice.


CONCLUSIONS
Chronic ethanol consumption increases the circulating level of leptin, and this is accompanied by altered expression of leptin-sensing molecules in the hypothalamus and peripheral adipose tissue. These results suggest that chronic ethanol intake affects metabolism by altering the leptin system that regulates energy balance.
Obradovic
Tanja
T
Cancer Prevention & Research Center, College of Pharmacy, and the Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164, USA.
Meadows
Gary G
GG
D000273:Adipose Tissue / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001823:Body Composition; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D007031:Hypothalamus / Q000737:chemistry / Q000378:metabolism*; D020738:Leptin / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000032:analysis
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C494080:Stat1 protein, mouse; C494087:Stat3 protein, mouse; D015534:Trans-Activators; C515447:leptin receptor, mouse; D000431:Ethanol