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C75 inhibits food intake by increasing CNS glucose metabolism

Nature Medicine volume 9, pages 483–485 (2003)Cite this article

To the editor

Energy homeostasis in mammals, including humans, is a robust process that matches caloric intake to caloric expenditure. Individuals detect and respond to sources of energy in their environment, and they ingest more or fewer food calories as appropriate for their needs. At a different level, individual cells have intricate and regulated pathways that monitor their metabolic needs and actively change their uptake and use of different energy sources (particularly fats and carbohydrates). Studies using compounds that alter metabolism, such as 2-deoxyglucose or the fatty-acid synthase (FAS) inhibitor C75 (refs. 1–6), show that cells of the central nervous system (CNS) have the ability to detect changes in available energy in the local environment and initiate appropriate behavioral and physiological responses. Considerable interest has been focused on the precise mechanism(s) enabling the cellular detection of metabolic status and its translation into neuronal signals. Recent reports that C75 decreases food intake and body weight imply that the FAS pathway is a key component of the connection between neuronal CNS metabolism and neuronal signaling1,2,3,4,5,6. Rats and mice respond to central (third-cerebral ventricular (i.c.v.)) or peripheral (intraperitoneal (i.p.)) C75 administration by reducing food intake, body weight and fat mass; this is true in genetically and diet-induced obese animals. Animals administered C75 eat little food, yet have a hypothalamic neuropeptide profile characteristic of the fed state1,2,3,4,5.

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Figure 1: Models in which CNS reliance on glucose metabolism is reduced, and effects of C75 are attenuated.

References

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Acknowledgements

These studies were supported by National Institutes of Health grants DK54890 and DK17844 and by Procter & Gamble. This work was approved by the University of Cincinnati Institutional Animal Care and Use Committee.

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Authors and Affiliations

  1. Department of Psychiatry, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

    Matthew D. Wortman, Deborah J. Clegg, Stephen C. Woods & Randy J. Seeley

  2. Department of Endocrinology, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA

    David D'Alessio

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  1. Matthew D. Wortman
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  2. Deborah J. Clegg
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Correspondence to Matthew D. Wortman.

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Our lab receives funds from an unrestricted education grant from Proctor & Gamble.

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Wortman, M., Clegg, D., D'Alessio, D. et al. C75 inhibits food intake by increasing CNS glucose metabolism. Nat Med 9, 483–485 (2003). https://doi.org/10.1038/nm0503-483

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