title: Meal pattern analysis in neural-specific proopiomelanocortin-deficient mice.
abstract: The central melanocortin system, consisting of melanocortin peptides, agouti gene related peptide and their receptors plays a critical role in the homeostatic control of energy balance. Loss of function mutations in the genes encoding proopiomelanocortin or melanocortin MC(4) receptors cause profound obesity and hyperphagia. However, little is known about the functional relationship of melanocortin neurocircuits to the temporal organization of meal-taking behavior. We used an operant paradigm that combined lever pressing for food pellet deliveries with free water intake monitored by lickometers to quantify meal patterns in mutant mice that selectively lack proopiomelanocortin expression in hypothalamic neurons (nPOMCKO). Compared to wildtype siblings, nPOMCKO mice consumed 50% more food and water daily and exhibited a more stereotyped feeding pattern characterized by reduced inter-meal and inter-mouse variations. Average meals were larger in size but shorter in duration, with no change in meal number. Consequently, intermeal intervals were prolonged in nPOMCKO mice. Similar patterns were observed in pre-obese juvenile and frankly obese adult mice suggesting that neither age nor degree of obesity was responsible for the altered phenotypes. Spontaneous locomotion and wheel running were decreased in nPOMCKO mice, but circadian variations in locomotor and feeding activity were conserved. These data show that hyperphagia in male nPOMCKO mice is due to increased meal size but not meal number, and this pattern is established by age of 5weeks. The combination of larger, more rapidly consumed meals and prolonged intermeal intervals suggests that proopiomelanocortin peptides are necessary for normal meal termination, but not the maintenance of satiety.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, United States.
authors.forename: Christian D
authors.initials: CD
authors.lastname: Richard
authors.forename: Virginie
authors.initials: V
authors.lastname: Tolle
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
mesh_terms: D000375:Aging / Q000378:metabolism / Q000502:physiology; D000818:Animals; D003216:Conditioning, Operant; D005247:Feeding Behavior / Q000502:physiology / Q000523:psychology; D055786:Gene Knockout Techniques; D006963:Hyperphagia / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D009043:Motor Activity; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D009928:Organ Specificity; D010902:Pituitary Gland / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000172:deficiency* / Q000235:genetics; D012420:Running
chemical_list: D011333:Pro-Opiomelanocortin