Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat.
In response to moderately increased dietary fat content, melanocortin-4 receptor-null mutant (MC4R-/-) mice exhibit hyperphagia and accelerated weight gain compared to wild-type mice. An increased feed efficiency (weight gain/kcal consumed) argues that mechanisms in addition to hyperphagia are instrumental in causing weight gain. We report two specific defects in coordinating energy expenditure with food intake in MC4R-/- mice. Wild-type mice respond to an increase in the fat content of the diet by rapidly increasing diet-induced thermogenesis and by increasing physical activity, neither of which are observed in MC4R-/- mice. Leptin-deficient and MC3R-/- mice regulate metabolic rate similarly to wild-type mice in this protocol. Melanocortinergic pathways involving MC4-R-regulated neurons, which rapidly respond to signals not requiring changes in leptin, thus seem to be important in regulating metabolic and behavioral responses to dietary fat.
Butler
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Vollum Institute, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA.
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Fan
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Kuhn
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Bartolome
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Cone
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D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D003433:Crosses, Genetic; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism; D005247:Feeding Behavior; D005260:Female; D006706:Homeostasis; D006963:Hyperphagia / Q000235:genetics*; D020738:Leptin / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005082:Physical Exertion; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D022722:Thermogenesis; D015430:Weight Gain
D004041:Dietary Fats; D020738:Leptin; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; D018043:Receptors, Corticotropin