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Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice

Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27 (−/−) mice and Fsp27/lep double...

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Autores principales: Toh, Shen Yon, Gong, Jingyi, Du, Guoli, Li, John Zhong, Yang, Shuqun, Ye, Jing, Yao, Huilan, Zhang, Yinxin, Xue, Bofu, Li, Qing, Yang, Hongyuan, Wen, Zilong, Li, Peng
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483355/
https://www.ncbi.nlm.nih.gov/pubmed/18682832
http://dx.doi.org/10.1371/journal.pone.0002890
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author Toh, Shen Yon
Gong, Jingyi
Du, Guoli
Li, John Zhong
Yang, Shuqun
Ye, Jing
Yao, Huilan
Zhang, Yinxin
Xue, Bofu
Li, Qing
Yang, Hongyuan
Wen, Zilong
Li, Peng
author_facet Toh, Shen Yon
Gong, Jingyi
Du, Guoli
Li, John Zhong
Yang, Shuqun
Ye, Jing
Yao, Huilan
Zhang, Yinxin
Xue, Bofu
Li, Qing
Yang, Hongyuan
Wen, Zilong
Li, Peng
author_sort Toh, Shen Yon
collection PubMed
description Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27 (−/−) mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27 (−/−) mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27 (−/−) mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27 (−/−) and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27 (−/−) mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1α were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27 (−/−) mice. Remarkably, Fsp27 (−/−) MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.
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spelling pubmed-24833552008-08-06 Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice Toh, Shen Yon Gong, Jingyi Du, Guoli Li, John Zhong Yang, Shuqun Ye, Jing Yao, Huilan Zhang, Yinxin Xue, Bofu Li, Qing Yang, Hongyuan Wen, Zilong Li, Peng PLoS One Research Article Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27 (−/−) mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs) from wildtype and Fsp27 (−/−) mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT) and white adipose tissue (WAT) and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27 (−/−) mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27 (−/−) and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27 (−/−) mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1α were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27 (−/−) mice. Remarkably, Fsp27 (−/−) MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3). Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity. Public Library of Science 2008-08-06 /pmc/articles/PMC2483355/ /pubmed/18682832 http://dx.doi.org/10.1371/journal.pone.0002890 Text en Toh 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Toh, Shen Yon
Gong, Jingyi
Du, Guoli
Li, John Zhong
Yang, Shuqun
Ye, Jing
Yao, Huilan
Zhang, Yinxin
Xue, Bofu
Li, Qing
Yang, Hongyuan
Wen, Zilong
Li, Peng
Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title_full Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title_fullStr Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title_full_unstemmed Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title_short Up-Regulation of Mitochondrial Activity and Acquirement of Brown Adipose Tissue-Like Property in the White Adipose Tissue of Fsp27 Deficient Mice
title_sort up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483355/
https://www.ncbi.nlm.nih.gov/pubmed/18682832
http://dx.doi.org/10.1371/journal.pone.0002890
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