title: Physical Activity, Energy Expenditure, and Defense of Body Weight in Melanocortin 4 Receptor-Deficient Male Rats.
abstract: Melanocortin 4 receptor (MC4R) variants contribute to human obesity, and rats lacking functional MC4R (Mc4rK314X/K314X) are obese. We investigated the hypothesis that low energy expenditure (EE) and physical activity contribute to this obese phenotype in male rats, and determined whether lack of functional MC4R conferred protection from weight loss during 50% calorie restriction. Though Mc4rK314X/K314Xrats showed low brown adipose Ucp1 expression and were less physically active than rats heterozygous for the mutation (Mc4r+/K314X) or wild-type (Mc4r+/+) rats, we found no evidence of lowered EE in Mc4rK314X/K314Xrats once body weight was taken into account using covariance. Mc4rK314X/K314Xrats had a significantly higher respiratory exchange ratio. Compared to Mc4r+/+rats, Mc4rK314X/K314Xand Mc4r+/K314Xrats lost less lean mass during calorie restriction, and less body mass when baseline weight was accounted for. Limited regional overexpression of Mc3r was found in the hypothalamus. Although lower physical activity levels in rats with nonfunctional MC4R did not result in lower total EE during free-fed conditions, rats lacking one or two functional copies of Mc4r showed conservation of mass, particularly lean mass, during energy restriction. This suggests that variants affecting MC4R function may contribute to individual differences in the metabolic response to food restriction.
authors.affiliation: College of Agriculture and Veterinary Medicine, Al-Qassim University, Buraydah, Al-Qassim Province, Saudi Arabia.|Department of Biological Sciences, Kent State University, Kent, OH, 44242, US.
authors.forename: Tariq I
authors.initials: TI
authors.lastname: Almundarij
authors.affiliation: School of Biomedical Sciences, Kent State University, Kent, OH, 44242, US.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Smyers
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH, 44242, US.
authors.forename: Addison
authors.initials: A
authors.lastname: Spriggs
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH, 44242, US.
authors.forename: Lydia A
authors.initials: LA
authors.lastname: Heemstra
authors.affiliation: Department of Natural Sciences, Malone University, Canton, OH, 44709, US.
authors.forename: Lisa
authors.initials: L
authors.lastname: Beltz
authors.affiliation: School of Biomedical Sciences, Kent State University, Kent, OH, 44242, US.|Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, US.
authors.forename: Eric
authors.initials: E
authors.lastname: Dyne
authors.affiliation: Department of Natural Sciences, Malone University, Canton, OH, 44709, US.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Ridenour
authors.affiliation: Department of Biological Sciences, Kent State University, Kent, OH, 44242, US.|School of Biomedical Sciences, Kent State University, Kent, OH, 44242, US.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Novak
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000235:genetics*; D031204:Caloric Restriction / Q000379:methods; D004734:Energy Metabolism / Q000235:genetics*; D015870:Gene Expression; D006579:Heterozygote; D006720:Homozygote; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D010641:Phenotype; D010805:Physical Conditioning, Animal; D051381:Rats; D055647:Rats, Transgenic; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency* / Q000235:genetics; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D044105:Receptor, Melanocortin, Type 4; C000604373:Ucp1 protein, rat; D000071256:Uncoupling Protein 1; C000613745:melanocortin receptor type 4, rat