دورية أكاديمية
Paradoxical leanness in the imprinting-centre deletion mouse model for Prader-Willi syndrome.
| العنوان: | Paradoxical leanness in the imprinting-centre deletion mouse model for Prader-Willi syndrome. |
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| المؤلفون: | Golding DM; School of BiosciencesCardiff University, Cardiff, UK., Rees DJ; Institute of Life SciencesCollege of Medicine, Swansea University, Swansea, UK., Davies JR; Behavioural Genetics GroupMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Schools of Medicine & Psychology, Cardiff University, Cardiff, UK., Relkovic D; Behavioural Genetics GroupMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Schools of Medicine & Psychology, Cardiff University, Cardiff, UK., Furby HV; Behavioural Genetics GroupMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Schools of Medicine & Psychology, Cardiff University, Cardiff, UK., Guschina IA; School of BiosciencesCardiff University, Cardiff, UK., Hopkins AL; School of BiosciencesCardiff University, Cardiff, UK., Davies JS; Institute of Life SciencesCollege of Medicine, Swansea University, Swansea, UK., Resnick JL; Center for Mammalian GeneticsUniversity of Florida, College of Medicine, Gainesville, Florida, USA., Isles AR; Behavioural Genetics GroupMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Schools of Medicine & Psychology, Cardiff University, Cardiff, UK., Wells T; School of BiosciencesCardiff University, Cardiff, UK wellst@cardiff.ac.uk. |
| المصدر: | The Journal of endocrinology [J Endocrinol] 2017 Jan; Vol. 232 (1), pp. 123-135. Date of Electronic Publication: 2016 Oct 31. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: BioScientifica Country of Publication: England NLM ID: 0375363 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1479-6805 (Electronic) Linking ISSN: 00220795 NLM ISO Abbreviation: J Endocrinol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Jan. 2011- : Bristol, UK : BioScientifica Original Publication: Bristol, UK : Society for Endocrinology |
| مواضيع طبية MeSH: | Mutation* , Phenotype*, Adipose Tissue, White/*metabolism , Body Weight/*physiology , Prader-Willi Syndrome/*genetics , Thinness/*genetics, Adipose Tissue, Brown/metabolism ; Animals ; DNA Methylation ; Disease Models, Animal ; Male ; Mice ; Sequence Deletion ; Thermogenesis/physiology |
| مستخلص: | Prader-Willi syndrome (PWS), a neurodevelopmental disorder caused by loss of paternal gene expression from 15q11-q13, is characterised by growth retardation, hyperphagia and obesity. However, as single gene mutation mouse models for this condition display an incomplete spectrum of the PWS phenotype, we have characterised the metabolic impairment in a mouse model for 'full' PWS, in which deletion of the imprinting centre (IC) abolishes paternal gene expression from the entire PWS cluster. We show that PWS-IC del mice displayed postnatal growth retardation, with reduced body weight, hyperghrelinaemia and marked abdominal leanness; proportionate retroperitoneal, epididymal/omental and inguinal white adipose tissue (WAT) weights being reduced by 82%, 84% and 67%, respectively. PWS-IC del mice also displayed a 48% reduction in proportionate interscapular brown adipose tissue (isBAT) weight with significant 'beiging' of abdominal WAT, and a 2°C increase in interscapular surface body temperature. Maintenance of PWS-IC del mice under thermoneutral conditions (30°C) suppressed the thermogenic activity in PWS-IC del males, but failed to elevate the abdominal WAT weight, possibly due to a normalisation of caloric intake. Interestingly, PWS-IC del mice also showed exaggerated food hoarding behaviour with standard and high-fat diets, but despite becoming hyperphagic when switched to a high-fat diet, PWS-IC del mice failed to gain weight. This evidence indicates that, unlike humans with PWS, loss of paternal gene expression from the PWS cluster in mice results in abdominal leanness. Although reduced subcutaneous insulation may lead to exaggerated heat loss and thermogenesis, abdominal leanness is likely to arise from a reduced lipid storage capacity rather than increased energy utilisation in BAT. (© 2017 The authors.) |
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| معلومات مُعتمدة: | G0801418 United Kingdom MRC_ Medical Research Council; MR/L010305/1 United Kingdom MRC_ Medical Research Council; BB/J016756/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
| فهرسة مساهمة: | Keywords: Prader–Willi syndrome; fat mass; food hoarding; thermogenesis |
| تواريخ الأحداث: | Date Created: 20161102 Date Completed: 20170626 Latest Revision: 20220129 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC5118940 |
| DOI: | 10.1530/JOE-16-0367 |
| PMID: | 27799465 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1479-6805 |
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| DOI: | 10.1530/JOE-16-0367 |