Characterization of the Hyperphagic Response to Dietary Fat in the MC4R Knockout Mouse

• DOI: 10.1210/en.2010-0716
• Publication Date: 2011-01-15T01:36:36Z
• Authors: Dollada Srisai; Matthew P. Gillum; Brandon L. Panaro; Xian-Man Zhang; Naiphinich Kotcha...; Gerald I. Shulman; Kate L. J. Ellacott; Roger D. Cone
• Keywords: Melanocortin 4 receptor; Knockout mouse

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 MC4R. This study validates MC4R+/− a model that, like MC4R−/−, also exhibits sustained response to dietary fat. Furthermore, both saturated monounsaturated fats elicit this response. N-acylphosphatidylethanolamine (NAPE) is lipid induced after several hours high-fat feeding, if dysregulated, might explain feeding behavior syndrome. Remarkably, MC4R−/− mice produce elevated levels NAPE are fully responsive anorexigenic activity oleoylethanolamide. Interestingly, additional differences N-acylethanolamine (NAE) biochemistry were seen animals, including reduced plasma NAE hypothalamic fatty acid amide hydrolase expression. Thus, while expression or does not hyperphagia syndrome, alterations family lipids evident. Analysis microstructure fat indicates that involves defective satiation an increased rate food intake, suggesting satiety enhanced reward value