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A phosphatidylinositol 3-kinase–phosphodiesterase 3B–cyclic AMP pathway in hypothalamic action of leptin on feeding

Nature Neuroscience volume 5, pages 727–728 (2002)Cite this article

Abstract

Using male Sprague-Dawley rats implanted with third intracerebroventricular (ICV) cannulae, we found that cilostamide, a phosphodiesterase 3 (PDE3) inhibitor, (i) reversed the established effects of leptin on food intake and body weight, (ii) blocked, at the hypothalamic level, the leptin-induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (Stat3) and (iii) blocked the DNA binding of p-Stat3. Additionally, ICV administration of leptin increased hypothalamic phosphatidylinositol 3-kinase (PI3K) and PDE3B activities and decreased cyclic AMP (cAMP) concentration. These results indicate that a PI3K–PDE3B–cAMP pathway interacting with the Janus kinase 2 (Jak2)–Stat3 pathway constitutes a critical component of leptin signaling in the hypothalamus.

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Figure 1: Cilostamide, a PDE3 inhibitor, reverses the satiety action of leptin in male rats that are fed ad libitum, but RO-20-1724, a PDE4 inhibitor, does not.
Figure 2: Cilostamide reversed the effect of leptin on body weight.
Figure 3: Cilostamide reverses the effect of leptin on Stat3 activation in the hypothalamus.

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Acknowledgements

This work was supported by a National Institutes of Health grant DK 52844 (to A.S.) and a Career & Development Award from the American Diabetes Association (to A.Z.).

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  1. Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, 3550 Terrace Street, Pittsburgh, 15261, Pennsylvania, USA

    Allan Z. Zhao, Jjing-Ning Huan, Sandhya Gupta, Rekha Pal & Abhiram Sahu

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  1. Allan Z. Zhao
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  2. Jjing-Ning Huan
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Correspondence to Abhiram Sahu.

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Zhao, A., Huan, JN., Gupta, S. et al. A phosphatidylinositol 3-kinase–phosphodiesterase 3B–cyclic AMP pathway in hypothalamic action of leptin on feeding. Nat Neurosci 5, 727–728 (2002). https://doi.org/10.1038/nn885

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