Leptin is a physiologically important regulator of food intake

Abstract

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 puri®ed 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 faafa 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 af®nity, 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 ®rst 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 faafa 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.

A peptide leptin antagonist reduces food intake in rodents

“…This conclusion is in accord with previous ®ndings, showing that polyclonal antibodies directed against leptin increase food intake in free-feeding lean rats. 22 The results of the present studies clearly show R128Q leptin to be an antagonist of leptin in vitro, but to behave as an agonist in vivo. The reason for this paradox is unclear at the present time.…”

“…Previous studies in free-feeding lean rats have shown that the injection of rabbit anti-mouse leptin antibodies into the brain markedly increases food intake during the light phase. 22 No increase in food intake was observed in obese Zucker faafa rats expressing a defective functional leptin receptor. These observations imply that the presence of leptin in the brain contributes tonically to the inhibition of food intake observed at this time.…”

“…guide cannulas, aimed at the right lateral ventricle, were stereotaxically implanted and correct placement was tested as previously described. 22 Injections were made in conscious free-moving rats.…”

“…These observations suggest, that in fed rats, endogenous leptin plays a physiologically important role to suppress food intake. 22 However, additional studies using other means of blocking the actions of leptin are needed before this conclusion can de®nitely be accepted.…”

“…13,16 ± 19 Although leptin can induce a decrease in food intake and body weight when injected either centrally or peripherally, the role of the endogenous peptide in the control of food intake and body weight remains unclear. In the only study to have directly addressed this question, 22 polyclonal antibodies directed against leptin were injected intracerebroventricularly (i.c.v.) into free-feeding rats, at the beginning of the light phase, when these animals normally do not eat.…”