Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat

Andrew A. Butler, Daniel L. Marks, Wei Fan, Cynthia M. Kuhn, Maria Bartolome, Roger D. Cone

Research output: Contribution to journalArticlepeer-review

277 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalNature Neuroscience
Issue number6
StatePublished - 2001

ASJC Scopus subject areas

  • Neuroscience(all)


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