Imperial College London
Alternate

Professor Dame Amanda Fisher

Faculty of Medicine, Institute of Clinical Sciences

Visiting Professor
 
 
 
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Contact

 

amanda.fisher

 
 
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Assistant

 

Ms Alessandra Lisini +44 (0)20 3313 8236

 
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Location

 

CRB (Clinical Research Building)Hammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Millership:2018:10.1016/j.molmet.2018.09.001,
author = {Millership, S and Tunster, SJ and Van, de Pette M and Choudhury, A and Irvine, E and Christian, M and Fisher, AG and John, RM and Scott, J and Withers, DJ},
doi = {10.1016/j.molmet.2018.09.001},
journal = {Molecular Metabolism},
pages = {97--106},
title = {Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice},
url = {http://dx.doi.org/10.1016/j.molmet.2018.09.001},
volume = {18},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - ObjectiveImprinted genes are crucial for the growth and development of fetal and juvenile mammals. Altered imprinted gene dosage causes a variety of human disorders, with growth and development during these crucial early stages strongly linked with future metabolic health in adulthood. Neuronatin (Nnat) is a paternally expressed imprinted gene found in neuroendocrine systems and white adipose tissue and is regulated by the diet and leptin. Neuronatin expression is downregulated in obese children and has been associated with stochastic obesity in C57BL/6 mice. However, our recent studies of Nnat null mice on this genetic background failed to display any body weight or feeding phenotypes but revealed a defect in glucose-stimulated insulin secretion due to the ability of neuronatin to potentiate signal peptidase cleavage of preproinsulin. Nnat deficiency in beta cells therefore caused a lack of appropriate storage and secretion of mature insulin.MethodsTo further explore the potential role of Nnat in the regulation of body weight and adiposity, we studied classical imprinting-related phenotypes such as placental, fetal, and postnatal growth trajectory patterns that may impact upon subsequent adult metabolic phenotypes.ResultsHere we find that, in contrast to the lack of any body weight or feeding phenotypes on the C57BL/6J background, deletion of Nnat in mice on 129S2/Sv background causes a postnatal growth restriction with reduced adipose tissue accumulation, followed by catch up growth after weaning. This was in the absence of any effect on fetal growth or placental development. In adult 129S2/Sv mice, Nnat deletion was associated with hyperphagia, reduced energy expenditure, and partial leptin resistance. Lack of neuronatin also potentiated obesity caused by either aging or high fat diet feeding.ConclusionsThe imprinted gene Nnat plays a key role in postnatal growth, adult energy homeostasis, and the pathogenesis of obesity via catch up growth effects, but this role
AU  - Millership,S
AU  - Tunster,SJ
AU  - Van,de Pette M
AU  - Choudhury,A
AU  - Irvine,E
AU  - Christian,M
AU  - Fisher,AG
AU  - John,RM
AU  - Scott,J
AU  - Withers,DJ
DO  - 10.1016/j.molmet.2018.09.001
EP  - 106
PY  - 2018///
SN  - 2212-8778
SP  - 97
TI  - Neuronatin deletion causes postnatal growth restriction and adult obesity in 129S2/Sv mice
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2018.09.001
UR  - http://hdl.handle.net/10044/1/63165
VL  - 18
ER  -
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