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Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats
- Source :
- Scientific Reports
- Publication Year :
- 2016
- Publisher :
- Nature Publishing Group, 2016.
-
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.
- Subjects :
- 0301 basic medicine
Male
medicine.medical_specialty
Adipose Tissue, White
Drinking
Adipose tissue
White adipose tissue
Carbohydrate metabolism
Biology
Kidney
Energy homeostasis
Article
Rats, Mutant Strains
Animals, Genetically Modified
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Eating
Gene Knockout Techniques
Adipocyte
Internal medicine
medicine
Animals
Homeostasis
Receptor
Multidisciplinary
Body Weight
Lipids
Rats
030104 developmental biology
Endocrinology
Glucose
chemistry
Liver
Receptor, Melanocortin, Type 4
Female
Melanocortin
Energy Metabolism
Receptor, Melanocortin, Type 3
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....e8a85f055ea4e998ba91d558b593fdd7