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Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18276-9. Epub 2007 Nov 6.

Leptin replacement alters brain response to food cues in genetically leptin-deficient adults.

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  • 1Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90024, USA.

Abstract

A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity.

PMID:
17986612
PMCID:
PMC2084333
DOI:
10.1073/pnas.0706481104
[PubMed - indexed for MEDLINE]
Free PMC Article
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