Publication: Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse
Issued Date
2011-03-01
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ISSN
00137227
00137227
00137227
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2-s2.0-79951934947
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Mahidol University
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SCOPUS
Bibliographic Citation
Endocrinology. Vol.152, No.3 (2011), 890-902
Suggested Citation
Dollada Srisai, Matthew P. Gillum, Brandon L. Panaro, Xian Man Zhang, Naiphinich Kotchabhakdi, Gerald I. Shulman, Kate L.J. Ellacott, Roger D. Cone Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse. Endocrinology. Vol.152, No.3 (2011), 890-902. doi:10.1210/en.2010-0716 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/11582
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Title
Characterization of the hyperphagic response to dietary fat in the MC4R knockout mouse
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Abstract
Defective melanocortin signaling causes hyperphagic obesity in humans and the melanocortin-4 receptor knockout mouse (MC4R -/- ). The human disease most commonly presents, however, as haploinsufficiency of the MC4R. This study validates the MC4R +/- mouse as a model of the human disease in that, like the MC4R -/- , the MC4R +/- mouse also exhibits a sustained hyperphagic response to dietary fat. Furthermore, both saturated and monounsaturated fats elicit this response. N-acylphosphatidylethanolamine (NAPE) is a signaling lipid induced after several hours of high-fat feeding, that, if dysregulated, might explain the feeding behavior in melanocortin obesity syndrome. Remarkably, however, MC4R -/- mice produce elevated levels of NAPE and are fully responsive to the anorexigenic activity of NAPE and oleoylethanolamide. Interestingly, additional differences in N-acylethanolamine (NAE) biochemistry were seen in MC4R -/- animals, including reduced plasma NAE levels and elevated hypothalamic levels of fatty acid amide hydrolase expression. Thus, while reduced expression of NAPE or NAE does not explain the high-fat hyperphagia in the melanocortin obesity syndrome, alterations in this family of signaling lipids are evident. Analysis of the microstructure of feeding behavior in response to dietary fat in the MC4R -/- and MC4R +/- mice indicates that the high-fat hyperphagia involves defective satiation and an increased rate of food intake, suggesting defective satiety signaling and enhanced reward value of dietary fat. Copyright © 2011 by The Endocrine Society.