| First Author | Golding DM | Year | 2017 |
| Journal | J Endocrinol | Volume | 232 |
| Issue | 1 | Pages | 123-135 |
| PubMed ID | 27799465 | Mgi Jnum | J:272083 |
| Mgi Id | MGI:6282591 | Doi | 10.1530/JOE-16-0367 |
| Citation | Golding DM, et al. (2017) Paradoxical leanness in the imprinting-centre deletion mouse model for Prader-Willi syndrome. J Endocrinol 232(1):123-135 |
| abstractText | 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 degrees C increase in interscapular surface body temperature. Maintenance of PWS-IC(del) mice under thermoneutral conditions (30 degrees 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. |
