Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

Abstract Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Irene Cimino, Debra Rimmington, Y. C. Loraine Tung, Katherine Lawler, Pierre Larraufie, Richard G. Kay, Samuel Virtue, Brian Y. H. Lam, Luca Fagnocchi, Marcella K. L. Ma, Vladimir Saudek, Ilona Zvetkova, Antonio Vidal-Puig, Giles S. H. Yeo, I. Sadaf Farooqi, J. Andrew Pospisilik, Fiona M. Gribble, Frank Reimann, Stephen O’Rahilly, Anthony P. Coll
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e7d5a888c2a540aeac4077803967b5d5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e7d5a888c2a540aeac4077803967b5d5
record_format	dspace
spelling	oai:doaj.org-article:e7d5a888c2a540aeac4077803967b5d52021-12-02T17:51:31ZMurine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity10.1038/s41598-021-96278-82045-2322https://doaj.org/article/e7d5a888c2a540aeac4077803967b5d52021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96278-8https://doaj.org/toc/2045-2322Abstract Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat +/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat +/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat +/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat +/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat +/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat +/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.Irene CiminoDebra RimmingtonY. C. Loraine TungKatherine LawlerPierre LarraufieRichard G. KaySamuel VirtueBrian Y. H. LamLuca FagnocchiMarcella K. L. MaVladimir SaudekIlona ZvetkovaAntonio Vidal-PuigGiles S. H. YeoI. Sadaf FarooqiJ. Andrew PospisilikFiona M. GribbleFrank ReimannStephen O’RahillyAnthony P. CollNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irene Cimino Debra Rimmington Y. C. Loraine Tung Katherine Lawler Pierre Larraufie Richard G. Kay Samuel Virtue Brian Y. H. Lam Luca Fagnocchi Marcella K. L. Ma Vladimir Saudek Ilona Zvetkova Antonio Vidal-Puig Giles S. H. Yeo I. Sadaf Farooqi J. Andrew Pospisilik Fiona M. Gribble Frank Reimann Stephen O’Rahilly Anthony P. Coll Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
description	Abstract Neuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat +/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat +/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat +/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat +/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat +/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat +/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.
format	article
author	Irene Cimino Debra Rimmington Y. C. Loraine Tung Katherine Lawler Pierre Larraufie Richard G. Kay Samuel Virtue Brian Y. H. Lam Luca Fagnocchi Marcella K. L. Ma Vladimir Saudek Ilona Zvetkova Antonio Vidal-Puig Giles S. H. Yeo I. Sadaf Farooqi J. Andrew Pospisilik Fiona M. Gribble Frank Reimann Stephen O’Rahilly Anthony P. Coll
author_facet	Irene Cimino Debra Rimmington Y. C. Loraine Tung Katherine Lawler Pierre Larraufie Richard G. Kay Samuel Virtue Brian Y. H. Lam Luca Fagnocchi Marcella K. L. Ma Vladimir Saudek Ilona Zvetkova Antonio Vidal-Puig Giles S. H. Yeo I. Sadaf Farooqi J. Andrew Pospisilik Fiona M. Gribble Frank Reimann Stephen O’Rahilly Anthony P. Coll
author_sort	Irene Cimino
title	Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
title_short	Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
title_full	Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
title_fullStr	Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
title_full_unstemmed	Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
title_sort	murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e7d5a888c2a540aeac4077803967b5d5
work_keys_str_mv	AT irenecimino murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT debrarimmington murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT yclorainetung murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT katherinelawler murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT pierrelarraufie murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT richardgkay murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT samuelvirtue murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT brianyhlam murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT lucafagnocchi murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT marcellaklma murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT vladimirsaudek murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT ilonazvetkova murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT antoniovidalpuig murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT gilesshyeo murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT isadaffarooqi murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT jandrewpospisilik murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT fionamgribble murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT frankreimann murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT stephenorahilly murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity AT anthonypcoll murineneuronatindeficiencyisassociatedwithahypervariablefoodintakeandbimodalobesity
_version_	1718379259716698112

Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

Ejemplares similares