A mouse model for a partially inactive obesity-associated human MC3R variant

We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) M...

Descripción completa

Detalles Bibliográficos
Autores principales: Lee, Bonggi, Koo, Jashin, Yun Jun, Joo, Gavrilova, Oksana, Lee, Yongjun, Seo, Arnold Y., Taylor-Douglas, Dezmond C., Adler-Wailes, Diane C., Chen, Faye, Gardner, Ryan, Koutzoumis, Dimitri, Sherafat Kazemzadeh, Roya, Roberson, Robin B., Yanovski, Jack A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738366/
https://www.ncbi.nlm.nih.gov/pubmed/26818770
http://dx.doi.org/10.1038/ncomms10522
_version_ 1782413599310872576
author Lee, Bonggi
Koo, Jashin
Yun Jun, Joo
Gavrilova, Oksana
Lee, Yongjun
Seo, Arnold Y.
Taylor-Douglas, Dezmond C.
Adler-Wailes, Diane C.
Chen, Faye
Gardner, Ryan
Koutzoumis, Dimitri
Sherafat Kazemzadeh, Roya
Roberson, Robin B.
Yanovski, Jack A.
author_facet Lee, Bonggi
Koo, Jashin
Yun Jun, Joo
Gavrilova, Oksana
Lee, Yongjun
Seo, Arnold Y.
Taylor-Douglas, Dezmond C.
Adler-Wailes, Diane C.
Chen, Faye
Gardner, Ryan
Koutzoumis, Dimitri
Sherafat Kazemzadeh, Roya
Roberson, Robin B.
Yanovski, Jack A.
author_sort Lee, Bonggi
collection PubMed
description We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3R(hWT/hWT). MC3R(hDM/hDM) mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs. MC3R(hDM/hDM) impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development.
format Online
Article
Text
id pubmed-4738366
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-47383662016-03-04 A mouse model for a partially inactive obesity-associated human MC3R variant Lee, Bonggi Koo, Jashin Yun Jun, Joo Gavrilova, Oksana Lee, Yongjun Seo, Arnold Y. Taylor-Douglas, Dezmond C. Adler-Wailes, Diane C. Chen, Faye Gardner, Ryan Koutzoumis, Dimitri Sherafat Kazemzadeh, Roya Roberson, Robin B. Yanovski, Jack A. Nat Commun Article We previously reported children homozygous for two MC3R sequence variants (C17A+G241A) have greater fat mass than controls. Here we show, using homozygous knock-in mouse models in which we replace murine Mc3r with wild-type human (MC3R(hWT/hWT)) and double-mutant (C17A+G241A) human (MC3R(hDM/hDM)) MC3R, that MC3R(hDM/hDM) have greater weight and fat mass, increased energy intake and feeding efficiency, but reduced length and fat-free mass compared with MC3R(hWT/hWT). MC3R(hDM/hDM) mice do not have increased adipose tissue inflammatory cell infiltration or greater expression of inflammatory markers despite their greater fat mass. Serum adiponectin levels are increased in MC3R(hDM/hDM) mice and MC3R(hDM/hDM) human subjects. MC3R(hDM/hDM) bone- and adipose tissue-derived mesenchymal stem cells (MSCs) differentiate into adipocytes that accumulate more triglyceride than MC3R(hWT/hWT) MSCs. MC3R(hDM/hDM) impacts nutrient partitioning to generate increased adipose tissue that appears metabolically healthy. These data confirm the importance of MC3R signalling in human metabolism and suggest a previously-unrecognized role for the MC3R in adipose tissue development. Nature Publishing Group 2016-01-28 /pmc/articles/PMC4738366/ /pubmed/26818770 http://dx.doi.org/10.1038/ncomms10522 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lee, Bonggi
Koo, Jashin
Yun Jun, Joo
Gavrilova, Oksana
Lee, Yongjun
Seo, Arnold Y.
Taylor-Douglas, Dezmond C.
Adler-Wailes, Diane C.
Chen, Faye
Gardner, Ryan
Koutzoumis, Dimitri
Sherafat Kazemzadeh, Roya
Roberson, Robin B.
Yanovski, Jack A.
A mouse model for a partially inactive obesity-associated human MC3R variant
title A mouse model for a partially inactive obesity-associated human MC3R variant
title_full A mouse model for a partially inactive obesity-associated human MC3R variant
title_fullStr A mouse model for a partially inactive obesity-associated human MC3R variant
title_full_unstemmed A mouse model for a partially inactive obesity-associated human MC3R variant
title_short A mouse model for a partially inactive obesity-associated human MC3R variant
title_sort mouse model for a partially inactive obesity-associated human mc3r variant
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738366/
https://www.ncbi.nlm.nih.gov/pubmed/26818770
http://dx.doi.org/10.1038/ncomms10522
work_keys_str_mv AT leebonggi amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT koojashin amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT yunjunjoo amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT gavrilovaoksana amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT leeyongjun amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT seoarnoldy amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT taylordouglasdezmondc amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT adlerwailesdianec amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT chenfaye amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT gardnerryan amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT koutzoumisdimitri amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT sherafatkazemzadehroya amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT robersonrobinb amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT yanovskijacka amousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT leebonggi mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT koojashin mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT yunjunjoo mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT gavrilovaoksana mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT leeyongjun mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT seoarnoldy mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT taylordouglasdezmondc mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT adlerwailesdianec mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT chenfaye mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT gardnerryan mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT koutzoumisdimitri mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT sherafatkazemzadehroya mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT robersonrobinb mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant
AT yanovskijacka mousemodelforapartiallyinactiveobesityassociatedhumanmc3rvariant

Ejemplares similares