Cargando…
GNB3 overexpression causes obesity and metabolic syndrome
The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716578/ https://www.ncbi.nlm.nih.gov/pubmed/29206867 http://dx.doi.org/10.1371/journal.pone.0188763 |
_version_ | 1783283977908387840 |
---|---|
author | Ozdemir, Alev Cagla Wynn, Grace M. Vester, Aimee Weitzmann, M. Neale Neigh, Gretchen N. Srinivasan, Shanthi Rudd, M. Katharine |
author_facet | Ozdemir, Alev Cagla Wynn, Grace M. Vester, Aimee Weitzmann, M. Neale Neigh, Gretchen N. Srinivasan, Shanthi Rudd, M. Katharine |
author_sort | Ozdemir, Alev Cagla |
collection | PubMed |
description | The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes. |
format | Online Article Text |
id | pubmed-5716578 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-57165782017-12-15 GNB3 overexpression causes obesity and metabolic syndrome Ozdemir, Alev Cagla Wynn, Grace M. Vester, Aimee Weitzmann, M. Neale Neigh, Gretchen N. Srinivasan, Shanthi Rudd, M. Katharine PLoS One Research Article The G-protein beta subunit 3 (GNB3) gene has been implicated in obesity risk; however, the molecular mechanism of GNB3-related disease is unknown. GNB3 duplication is responsible for a syndromic form of childhood obesity, and an activating DNA sequence variant (C825T) in GNB3 is also associated with obesity. To test the hypothesis that GNB3 overexpression causes obesity, we created bacterial artificial chromosome (BAC) transgenic mice that carry an extra copy of the human GNB3 risk allele. Here we show that GNB3-T/+ mice have increased adiposity, but not greater food intake or a defect in satiety. GNB3-T/+ mice have elevated fasting plasma glucose, insulin, and C-peptide, as well as glucose intolerance, indicating type 2 diabetes. Fasting plasma leptin, triglycerides, cholesterol and phospholipids are elevated, suggesting metabolic syndrome. Based on a battery of behavioral tests, GNB3-T/+ mice did not exhibit anxiety- or depressive-like phenotypes. GNB3-T/+ and wild-type animals have similar activity levels and heat production; however, GNB3-T/+ mice exhibit dysregulation of acute thermogenesis. Finally, Ucp1 expression is significantly lower in white adipose tissue (WAT) in GNB3-T/+ mice, suggestive of WAT remodeling that could lead to impaired cellular thermogenesis. Taken together, our study provides the first functional link between GNB3 and obesity, and presents insight into novel pathways that could be applied to combat obesity and type 2 diabetes. Public Library of Science 2017-12-05 /pmc/articles/PMC5716578/ /pubmed/29206867 http://dx.doi.org/10.1371/journal.pone.0188763 Text en © 2017 Ozdemir et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ozdemir, Alev Cagla Wynn, Grace M. Vester, Aimee Weitzmann, M. Neale Neigh, Gretchen N. Srinivasan, Shanthi Rudd, M. Katharine GNB3 overexpression causes obesity and metabolic syndrome |
title | GNB3 overexpression causes obesity and metabolic syndrome |
title_full | GNB3 overexpression causes obesity and metabolic syndrome |
title_fullStr | GNB3 overexpression causes obesity and metabolic syndrome |
title_full_unstemmed | GNB3 overexpression causes obesity and metabolic syndrome |
title_short | GNB3 overexpression causes obesity and metabolic syndrome |
title_sort | gnb3 overexpression causes obesity and metabolic syndrome |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5716578/ https://www.ncbi.nlm.nih.gov/pubmed/29206867 http://dx.doi.org/10.1371/journal.pone.0188763 |
work_keys_str_mv | AT ozdemiralevcagla gnb3overexpressioncausesobesityandmetabolicsyndrome AT wynngracem gnb3overexpressioncausesobesityandmetabolicsyndrome AT vesteraimee gnb3overexpressioncausesobesityandmetabolicsyndrome AT weitzmannmneale gnb3overexpressioncausesobesityandmetabolicsyndrome AT neighgretchenn gnb3overexpressioncausesobesityandmetabolicsyndrome AT srinivasanshanthi gnb3overexpressioncausesobesityandmetabolicsyndrome AT ruddmkatharine gnb3overexpressioncausesobesityandmetabolicsyndrome |