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CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance

Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CR...

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Autores principales: Tian, Xiaoxiang, Yan, Chenghui, Liu, Meili, Zhang, Quanyu, Liu, Dan, Liu, Yanxia, Li, Shaohua, Han, Yaling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411056/
https://www.ncbi.nlm.nih.gov/pubmed/28459882
http://dx.doi.org/10.1371/journal.pone.0176873
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author Tian, Xiaoxiang
Yan, Chenghui
Liu, Meili
Zhang, Quanyu
Liu, Dan
Liu, Yanxia
Li, Shaohua
Han, Yaling
author_facet Tian, Xiaoxiang
Yan, Chenghui
Liu, Meili
Zhang, Quanyu
Liu, Dan
Liu, Yanxia
Li, Shaohua
Han, Yaling
author_sort Tian, Xiaoxiang
collection PubMed
description Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CREG1 leads to early embryonic death, suggesting that it is essential for early development. In the analysis of Creg1 heterozygous mice, we unexpectedly observed that they developed obesity as they get older. In this study, we further studied this phenotype by feeding wild type (WT) and Creg1 heterozygote (Creg1(+/-)) mice a high fat diet (HFD) for 16 weeks. Our data showed that Creg1(+/-) mice exhibited a more prominent obesity phenotype with no change in food intake compared with WT controls when challenged with HFD. Creg1 haploinsufficiency also exacerbated HFD-induced liver steatosis, dyslipidemia and insulin resistance. In addition, HFD markedly increased pro-inflammatory cytokines in plasma and epididymal adipose tissue in Creg1(+/-) mice as compared with WT controls. The activation level of NF-κB, a major regulator of inflammatory response, in epididymal adipose tissue was also elevated in parallel with the cytokines in Creg1(+/-) mice. These pro-inflammatory responses elicited by CREG1 reduction were confirmed in 3T3-L1-derived adipocytes with CREG1 depletion by siRNA transfection. Given that adipose tissue inflammation has been shown to play a key role in obesity-induced insulin resistance and metabolic syndrome, our results suggest that Creg1 haploinsufficiency confers increased susceptibility of adipose tissue to inflammation, leading to aggravated obesity and insulin resistance when challenged with HFD. This study uncovered a novel function of CREG1 in metabolic disorders.
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spelling pubmed-54110562017-05-12 CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance Tian, Xiaoxiang Yan, Chenghui Liu, Meili Zhang, Quanyu Liu, Dan Liu, Yanxia Li, Shaohua Han, Yaling PLoS One Research Article Cellular repressor of E1A-stimulated genes 1 (CREG1) is a small glycoprotein whose physiological function is unknown. In cell culture studies, CREG1 promotes cellular differentiation and maturation. To elucidate its physiological functions, we deleted the Creg1 gene in mice and found that loss of CREG1 leads to early embryonic death, suggesting that it is essential for early development. In the analysis of Creg1 heterozygous mice, we unexpectedly observed that they developed obesity as they get older. In this study, we further studied this phenotype by feeding wild type (WT) and Creg1 heterozygote (Creg1(+/-)) mice a high fat diet (HFD) for 16 weeks. Our data showed that Creg1(+/-) mice exhibited a more prominent obesity phenotype with no change in food intake compared with WT controls when challenged with HFD. Creg1 haploinsufficiency also exacerbated HFD-induced liver steatosis, dyslipidemia and insulin resistance. In addition, HFD markedly increased pro-inflammatory cytokines in plasma and epididymal adipose tissue in Creg1(+/-) mice as compared with WT controls. The activation level of NF-κB, a major regulator of inflammatory response, in epididymal adipose tissue was also elevated in parallel with the cytokines in Creg1(+/-) mice. These pro-inflammatory responses elicited by CREG1 reduction were confirmed in 3T3-L1-derived adipocytes with CREG1 depletion by siRNA transfection. Given that adipose tissue inflammation has been shown to play a key role in obesity-induced insulin resistance and metabolic syndrome, our results suggest that Creg1 haploinsufficiency confers increased susceptibility of adipose tissue to inflammation, leading to aggravated obesity and insulin resistance when challenged with HFD. This study uncovered a novel function of CREG1 in metabolic disorders. Public Library of Science 2017-05-01 /pmc/articles/PMC5411056/ /pubmed/28459882 http://dx.doi.org/10.1371/journal.pone.0176873 Text en © 2017 Tian 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
Tian, Xiaoxiang
Yan, Chenghui
Liu, Meili
Zhang, Quanyu
Liu, Dan
Liu, Yanxia
Li, Shaohua
Han, Yaling
CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title_full CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title_fullStr CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title_full_unstemmed CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title_short CREG1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
title_sort creg1 heterozygous mice are susceptible to high fat diet-induced obesity and insulin resistance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5411056/
https://www.ncbi.nlm.nih.gov/pubmed/28459882
http://dx.doi.org/10.1371/journal.pone.0176873
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