Intraventricular Leptin Reduces Food Intake and Body Weight of Lean Rats but Not Obese Zucker Rats

R. J. Seeley; G. van Dijk; L. A. Campfield; F. J. Smith; P. Burn; J. A. Nelligan; S. M. Bell; D. G. Baskin; S. C. Woods; M. W. Schwartz

doi:10.1055/s-2007-979874

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 1996; 28(12): 664-668
DOI: 10.1055/s-2007-979874

Originals Basic

Intraventricular Leptin Reduces Food Intake and Body Weight of Lean Rats but Not Obese Zucker Rats

R. J. Seeley¹ , G. van Dijk¹ , L. A. Campfield⁴ , F. J. Smith⁴ , P. Burn⁴ , J. A. Nelligan¹ , S. M. Bell¹ , D. G. Baskin³ , S. C. Woods¹ ^, ² , M. W. Schwartz²

¹Department of Psychology, University of Washington and Seattle Veterans Affairs Medical Center, Seattle, WA, U.S.A.
²Department of Medicine, University of Washington and Seattle Veterans Affairs Medical Center, Seattle, WA, U.S.A.
³Department of Biological Structure, University of Washington and Seattle Veterans Affairs Medical Center, Seattle, WA, U.S.A.
⁴Department of Metabolic Diseases, Hoffmann-La Roche Inc., Nutley, NJ, U.S.A.

Abstract

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Abstract

The protein encoded by the obese (ob) gene, leptin, is secreted from adipose tissue and is proposed to act in the brain as an important regulator of food intake and body weight. To investigate the direct effects of leptin within the CNS, we injected 3.5 µg of either mouse or human leptin into the third ventricle (ICV) of lean Long-Evans rats or obese (fa/fa) Zucker rats, in which obesity results from a mutation in the leptin receptor gene. CV administration of leptin reduced 4-h food intake in both deprived and non-deprived lean rats. In addition, repeated ICV administration produced a long-lasting reduction in body weight while peripheral administration of the same dose had no effect. ICV administration of the same dose of leptin into the third ventricle of obese Zucker rats did not reduce food intake. These results are consistent with the hypothesis that leptin has direct actions in the CNS as an afferent signal related to the state of energy stores in adipose tissue. Furthermore, insensitivity to these central effects of leptin may be an important determinant of obesity.

Key words

ob gene product - body energy balance - central nervous system - obesity - Zucker rat

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