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Leptin regulates the reward value of nutrient

Nature Neuroscience volume 14, pages 1562–1568 (2011)Cite this article

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Abstract

We developed an assay for quantifying the reward value of nutrient and used it to analyze the effects of metabolic state and leptin. In this assay, mice chose between two sippers, one of which dispensed water and was coupled to optogenetic activation of dopaminergic (DA) neurons and the other of which dispensed natural or artificial sweeteners. This assay measured the reward value of sweeteners relative to lick-induced optogenetic activation of DA neurons. Mice preferred optogenetic stimulation of DA neurons to sucralose, but not to sucrose. However, the mice preferred sucralose plus optogenetic stimulation versus sucrose. We found that food restriction increased the value of sucrose relative to sucralose plus optogenetic stimulation, and that leptin decreased it. Our data suggest that leptin suppresses the ability of sucrose to drive taste-independent DA neuronal activation and provide new insights into the mechanism of leptin's effects on food intake.

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Figure 1: Optogenetic activation of DA neurons.
Figure 2: The optogenetic licking assay drives voluntary ingestion in nondeprived mice.
Figure 3: Sucrose has higher value than sucralose.
Figure 4: Optogenetic activation of DA neurons reverses the preference of sucrose over sucralose and elicits activation of DA neurons.
Figure 5: Fasting increases the value of sucrose, and leptin reverses this effect.
Figure 6: Leptin corrects the fasting-induced increase in the value of sucrose via the CNS.
Figure 7: Leptin supresses post-ingestive sucrose-induced DA neuron activation.

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Acknowledgements

We thank F. Pestilli for helping with the bootstrap analysis. We thank the Klarman Family Foundation for Eating Disorders (KFFfED) for supporting this work. A.I.D. was supported by Fundação para a Ciência e Tecnologia (Portugal) and KFFfED. J.V. was supported by KFFfED. X.R. and I.E.d.A. were supported by US National Institutes of Health grant DC009997 to I.E.d.A. F.Z., V.G. and K.D. were supported by the US National Institutes of Health (grant MH075957), the Gatsby Foundation and Defense Advanced Research Projects Agency. H.U.V. was partially supported by the Nancy M. and Samuel C. Fleming Research Scholar Award in Intercampus Collaborations.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Genetics, Rockefeller University, New York, New York, USA

    Ana I Domingos, Jake Vaynshteyn & Jeffrey Friedman

  2. Department of Radiology, Weill Cornell Medical College, New York, New York, USA

    Henning U Voss

  3. The J. B. Pierce Laboratory and Department of Psychiatry, Yale University School of Medicine, Yale University, New Haven, Connecticut, USA

    Xueying Ren & Ivan E de Araujo

  4. Department of Bioengineering, Stanford University, Stanford, California, USA

    Viviana Gradinaru, Feng Zang & Karl Deisseroth

  5. Howard Hughes Medical Institute, Stanford University, Stanford, California, USA

    Karl Deisseroth

  6. CNC Program, Stanford University, Stanford, California, USA

    Karl Deisseroth

  7. Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA

    Karl Deisseroth

  8. Howard Hughes Medical Institute, Rockefeller University, New York, New York, USA

    Jeffrey Friedman

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  1. Ana I Domingos
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  4. Xueying Ren
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Contributions

A.I.D. contributed to all data. J.V. collected behavioral data. H.U.V. collected and analyzed the ofMRI data and generated the graphs and statistical parametric maps in Figure 1c,d. F.Z., V.G. and K.D. provided viral vectors. X.R. and I.E.d.A. contributed to Figure 2a. A.D., I.E.d.A. and J.F. wrote the manuscript.

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Correspondence to Jeffrey Friedman.

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The authors declare no competing financial interests.

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Domingos, A., Vaynshteyn, J., Voss, H. et al. Leptin regulates the reward value of nutrient. Nat Neurosci 14, 1562–1568 (2011). https://doi.org/10.1038/nn.2977

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