RT Journal Article
SR Electronic
T1 The Melanocortin-3 Receptor Is Required for Entrainment to Meal Intake
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12946
OP 12955
DO 10.1523/JNEUROSCI.3615-08.2008
VO 28
IS 48
A1 Gregory M. Sutton
A1 Diego Perez-Tilve
A1 Ruben Nogueiras
A1 Jidong Fang
A1 Jason K. Kim
A1 Roger D. Cone
A1 Jeffrey M. Gimble
A1 Matthias H. Tschöp
A1 Andrew A. Butler
YR 2008
UL http://www.jneurosci.org/content/28/48/12946.abstract
AB Entrainment of anticipatory activity and wakefulness to nutrient availability is a poorly understood component of energy homeostasis. Restricted feeding (RF) paradigms with a periodicity of 24 h rapidly induce entrainment of rhythms anticipating food presentation that are independent of master clocks in the suprachiasmatic nucleus (SCN) but do require other hypothalamic structures. Here, we report that the melanocortin system, which resides in hypothalamic structures required for food entrainment, is required for expression of food entrainable rhythms. Food anticipatory activity was assessed in wild-type (WT) and melanocortin-3 receptor-deficient (Mc3r−/−) C57BL/J mice by wheel running, spontaneous locomotory movement, and measurement of wakefulness. WT mice housed in wheel cages subject to RF exhibited increased wheel activity during the 2 h preceding meal presentation, which corresponded with an increase in wakefulness around meal time and reduced wakefulness during the dark. WT mice also exhibited increased x- and z-movements centered around food initiation. The activity-based responses to RF were significantly impaired in mice lacking Mc3r. RF also failed to increase wakefulness in the 2 h before food presentation in Mc3r−/− mice. Food entrainment requires expression of Neuronal PAS domain 2 (Npas2) and Period2 (Per2) genes, components of the transcriptional machinery maintaining a clock rhythm. Analysis of cortical gene expression revealed severe abnormalities in rhythmic expression of clock genes (Bmal1, Npas2, Per2) under ad libitum and RF conditions. In summary, Mc3r are required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for normal regulation of cortical clock function.