Paradoxical leanness in the imprinting-centre deletion mouse model for Prader-Willi syndrome
| Autor: | David M, Golding, Daniel J, Rees, Jennifer R, Davies, Dinko, Relkovic, Hannah V, Furby, Irina A, Guschina, Anna L, Hopkins, Jeffrey S, Davies, James L, Resnick, Anthony R, Isles, Timothy, Wells |
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| Rok vydání: | 2016 |
| Předmět: |
Male
congenital hereditary and neonatal diseases and abnormalities Prader–Willi syndrome Adipose Tissue White Research food hoarding Body Weight nutritional and metabolic diseases Thermogenesis fat mass DNA Methylation nervous system diseases Disease Models Animal Mice Phenotype Adipose Tissue Brown Thinness Mutation Animals Prader-Willi Syndrome Sequence Deletion |
| Zdroj: | The Journal of Endocrinology |
| ISSN: | 1479-6805 |
| Popis: | 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-ICdel 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-ICdel 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-ICdel mice under thermoneutral conditions (30°C) suppressed the thermogenic activity in PWS-ICdel males, but failed to elevate the abdominal WAT weight, possibly due to a normalisation of caloric intake. Interestingly, PWS-ICdel 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-ICdel 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. |
| Databáze: | OpenAIRE |
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