title: Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats.
abstract: Melanocortin-3 and 4 receptors (MC3R and MC4R) can regulate energy homeostasis, but their respective roles especially the functions of MC3R need more exploration. Here Mc3r and Mc4r single and double knockout (DKO) rats were generated using CRISPR-Cas9 system. Metabolic phenotypes were examined and data were compared systematically. Mc3r KO rats displayed hypophagia and decreased body weight, while Mc4r KO and DKO exhibited hyperphagia and increased body weight. All three mutants showed increased white adipose tissue mass and adipocyte size. Interestingly, although Mc3r KO did not show a significant elevation in lipids as seen in Mc4r KO, DKO displayed even higher lipid levels than Mc4r KO. DKO also showed more severe glucose intolerance and hyperglycaemia than Mc4r KO. These data demonstrated MC3R deficiency caused a reduction of food intake and body weight, whereas at the same time exhibited additive effects on top of MC4R deficiency on lipid and glucose metabolism. This is the first phenotypic analysis and systematic comparison of Mc3r KO, Mc4r KO and DKO rats on a homogenous genetic background. These mutant rats will be important in defining the complicated signalling pathways of MC3R and MC4R. Both Mc4r KO and DKO are good models for obesity and diabetes research.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: You
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Handan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Tongtong
authors.initials: T
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Roumei
authors.initials: R
authors.lastname: Xing
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Yanjiao
authors.initials: Y
authors.lastname: Shao
authors.affiliation: School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Dali
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.
authors.forename: Huaqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, Shanghai 200241, China.|Institute of Biosciences and Technology, Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, Houston, Texas 77030, USA.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D052436:Adipose Tissue, White / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified; D001835:Body Weight; D004326:Drinking; D004435:Eating; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005260:Female; D055786:Gene Knockout Techniques; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007668:Kidney / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D044104:Receptor, Melanocortin, Type 3 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D044105:Receptor, Melanocortin, Type 4 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism
chemical_list: D008055:Lipids; D044104:Receptor, Melanocortin, Type 3; D044105:Receptor, Melanocortin, Type 4; C514973:melanocortin 3 receptor, rat; C000613745:melanocortin receptor type 4, rat; D005947:Glucose