Leptin is a physiologically important regulator of food intake.
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.


METHODS
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.


CONCLUSIONS
Endogenous leptin acting within the brain plays a physiologically important role in the control of food intake in lean rats.
Brunner
L
L
Novartis Pharma AG Basel, Switzerland.
Nick
H P
HP
Cumin
F
F
Chiesi
M
M
Baum
H P
HP
Whitebread
S
S
Stricker-Krongrad
A
A
Levens
N
N
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001835:Body Weight / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D000939:Epitopes; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D020738:Leptin; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D011506:Proteins / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013997:Time Factors
D000906:Antibodies; D000939:Epitopes; D007074:Immunoglobulin G; D020738:Leptin; D011506:Proteins