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Neurotensin agonists in the regulation of food intake

International Journal of Obesity volume 38, page 474 (2014)Cite this article

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We read with interest the review by Hussain and Bloom1 regarding the important interactions between the gut and brain. Unfortunately, neurotensin was dismissed by the authors as a putative target for anti-obesity therapy based on a single citation.2 Cooke et al.2 injected native neurotensin intraperitoneally, and found the effect to be transient. This finding was consistent with tachyphylaxis as well as the rapid degradation of neurotensin given peripherally.

In contrast, neurotensin analog agonists (mostly based on NT8-13) are able to penetrate the central nervous system following peripheral administration. These compounds have sustained effects on food intake. Work from our laboratory3 demonstrated a persistent, dose-dependent reduction in weight gain in both Sprague–Dawley and genetically obese Zucker rats. These trials were from 15 to 38 days with intraperitoneal administration of NT69L, which binds nonselectively to NTS1 and NTS2 receptors. More recently, Feifel et al.4 found that daily intraperitoneal injections of PD149163, another NT8-13 analog, suppressed food intake and body weight over 10 days, without the development of tolerance.

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References

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Authors and Affiliations

  1. Department of Psychiatry and Psychology, Neuropsychopharmacology Laboratory, Mayo Foundation for Medical Education and Research, Mayo Clinic, Jacksonville, FL, USA

    P Fredrickson, M Boules & E Richelson

Authors
  1. P Fredrickson
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  2. M Boules
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  3. E Richelson
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Corresponding author

Correspondence to P Fredrickson.

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Competing interests

The authors are co-inventors of neurotensin analogs, for which U.S. Patents have been issued and licensed by Mayo Clinic Medical Ventures to a commercial firm (Sarentis Therapeutics Inc.).

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Fredrickson, P., Boules, M. & Richelson, E. Neurotensin agonists in the regulation of food intake. Int J Obes 38, 474 (2014). https://doi.org/10.1038/ijo.2013.129

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