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Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance
The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478538/ https://www.ncbi.nlm.nih.gov/pubmed/22807031 http://dx.doi.org/10.2337/db12-0169 |
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author | Liu, Meilian Xiang, Ruihua Wilk, Sarah Ann Zhang, Ning Sloane, Lauren B. Azarnoush, Kian Zhou, Lijun Chen, Hongzhi Xiang, Guangda Walter, Christi A. Austad, Steven N. Musi, Nicolas DeFronzo, Ralph A. Asmis, Reto Scherer, Philipp E. Dong, Lily Q. Liu, Feng |
author_facet | Liu, Meilian Xiang, Ruihua Wilk, Sarah Ann Zhang, Ning Sloane, Lauren B. Azarnoush, Kian Zhou, Lijun Chen, Hongzhi Xiang, Guangda Walter, Christi A. Austad, Steven N. Musi, Nicolas DeFronzo, Ralph A. Asmis, Reto Scherer, Philipp E. Dong, Lily Q. Liu, Feng |
author_sort | Liu, Meilian |
collection | PubMed |
description | The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad(−/−)). In addition, the fDsbA-L/Ad(−/−) mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. |
format | Online Article Text |
id | pubmed-3478538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-34785382013-11-01 Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance Liu, Meilian Xiang, Ruihua Wilk, Sarah Ann Zhang, Ning Sloane, Lauren B. Azarnoush, Kian Zhou, Lijun Chen, Hongzhi Xiang, Guangda Walter, Christi A. Austad, Steven N. Musi, Nicolas DeFronzo, Ralph A. Asmis, Reto Scherer, Philipp E. Dong, Lily Q. Liu, Feng Diabetes Obesity Studies The antidiabetic and antiatherosclerotic effects of adiponectin make it a desirable drug target for the treatment of metabolic and cardiovascular diseases. However, the adiponectin-based drug development approach turns out to be difficult due to extremely high serum levels of this adipokine. On the other hand, a significant correlation between adiponectin multimerization and its insulin-sensitizing effects has been demonstrated, suggesting a promising alternative therapeutic strategy. Here we show that transgenic mice overexpressing disulfide bond A oxidoreductase-like protein in fat (fDsbA-L) exhibited increased levels of total and the high-molecular-weight form of adiponectin compared with wild-type (WT) littermates. The fDsbA-L mice also displayed resistance to diet-induced obesity, insulin resistance, and hepatic steatosis compared with WT control mice. The protective effects of DsbA-L overexpression on diet-induced insulin resistance, but not increased body weight and fat cell size, were significantly decreased in adiponectin-deficient fDsbA-L mice (fDsbA-L/Ad(−/−)). In addition, the fDsbA-L/Ad(−/−) mice displayed greater activity and energy expenditure compared with adiponectin knockout mice under a high-fat diet. Taken together, our results demonstrate that DsbA-L protects mice from diet-induced obesity and insulin resistance through adiponectin-dependent and independent mechanisms. In addition, upregulation of DsbA-L could be an effective therapeutic approach for the treatment of obesity and its associated metabolic disorders. American Diabetes Association 2012-11 2012-10-16 /pmc/articles/PMC3478538/ /pubmed/22807031 http://dx.doi.org/10.2337/db12-0169 Text en © 2012 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. |
spellingShingle | Obesity Studies Liu, Meilian Xiang, Ruihua Wilk, Sarah Ann Zhang, Ning Sloane, Lauren B. Azarnoush, Kian Zhou, Lijun Chen, Hongzhi Xiang, Guangda Walter, Christi A. Austad, Steven N. Musi, Nicolas DeFronzo, Ralph A. Asmis, Reto Scherer, Philipp E. Dong, Lily Q. Liu, Feng Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title | Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title_full | Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title_fullStr | Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title_full_unstemmed | Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title_short | Fat-Specific DsbA-L Overexpression Promotes Adiponectin Multimerization and Protects Mice From Diet-Induced Obesity and Insulin Resistance |
title_sort | fat-specific dsba-l overexpression promotes adiponectin multimerization and protects mice from diet-induced obesity and insulin resistance |
topic | Obesity Studies |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3478538/ https://www.ncbi.nlm.nih.gov/pubmed/22807031 http://dx.doi.org/10.2337/db12-0169 |
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