Leptin is a physiologically important regulator of food intake

被引:47
作者
Brunner, L [1 ]
Nick, HP [1 ]
Cumin, F [1 ]
Chiesi, M [1 ]
Baum, HP [1 ]
Whitebread, S [1 ]
StrickerKrongrad, A [1 ]
Levens, N [1 ]
机构
[1] NOVARTIS PHARMA AG, METAB & CARDIOVASC DIS RES, OBES PHARMACOL, OBES MOL & CELL BIOL, BASEL, SWITZERLAND
关键词
Zucker fatty fa/fa rats; leptin antibodies; leptin; lean rats; leptin receptors;
D O I
10.1038/sj.ijo.0800529
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE: These studies were designed to test the hypothesis that endogenous leptin, acting within the brain plays a physiologically important role in the control of food intake in lean rats. DESIGN: Antibodies directed against mouse leptin were raised in rabbits. The purified IgG fractions prepared from pre-immune and immune sera were injected into the right lateral ventricle of lean Sprague-Dawley rats and obese Zucker fatty fa/fa rats. Changes in food intake were measured over the following 20 h period. RESULTS: The anti-leptin antibodies recognized a major epitope in the C-terminal region of the leptin molecule. The antibodies bound both mouse and rat leptin with high affinity, but did not bind human leptin, or a selected range of other hormones and neurotransmitters known to affect food intake. In competition studies, the binding of mouse, but not human leptin to the human Ob-Rb receptor was prevented by the antibodies. This indicates that the antibodies can block the action of leptin by preventing its binding to the Ob-Rb receptor, Injection of the anti-leptin antibodies into the brain of lean rats led to an increase in food intake during the first hour after injection which was not compensated during the following 19 h period. Injection of the anti-leptin antibodies did not affect food intake in Zucker fatty fa/fa rats which express an abnormal Ob-Rb receptor. CONCLUSION: Endogenous leptin acting within the brain plays a physiologically important role in the control of food intake in lean rats.
引用
收藏
页码:1152 / 1160
页数:9
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