FADD is a key regulator of lipid metabolism
Abstract FADD, a classical apoptotic signaling adaptor, was recently reported to have non‐apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR‐α is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP...
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| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2016-06-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.201505924 |
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| author | Hongqin Zhuang Xueshi Wang Daolong Zha Ziyi Gan Fangfang Cai Pan Du Yunwen Yang Bingya Yang Xiangyu Zhang Chun Yao Yuqiang Zhou Chizhou Jiang Shengwen Guan Xuerui Zhang Jing Zhang Wenhui Jiang Qingang Hu Zi‐Chun Hua |
| author_facet | Hongqin Zhuang Xueshi Wang Daolong Zha Ziyi Gan Fangfang Cai Pan Du Yunwen Yang Bingya Yang Xiangyu Zhang Chun Yao Yuqiang Zhou Chizhou Jiang Shengwen Guan Xuerui Zhang Jing Zhang Wenhui Jiang Qingang Hu Zi‐Chun Hua |
| author_sort | Hongqin Zhuang |
| collection | DOAJ |
| description | Abstract FADD, a classical apoptotic signaling adaptor, was recently reported to have non‐apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR‐α is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP140, which is a corepressor for PPAR‐α, and FADD phosphorylation‐mimic mutation (FADD‐D) or FADD deficiency abolishes RIP140‐mediated transcriptional repression, leading to the activation of PPAR‐α. FADD‐D‐mutant mice exhibit significantly decreased adipose tissue mass and triglyceride accumulation. Also, they exhibit increased energy expenditure with enhanced fatty acid oxidation in adipocytes due to the activation of PPAR‐α. Similar metabolic phenotypes, such as reduced fat formation, insulin resistance, and resistance to HFD‐induced obesity, are shown in adipose‐specific FADD knockout mice. Additionally, FADD‐D mutation can reverse the severe genetic obesity phenotype of ob/ob mice, with elevated fatty acid oxidation and oxygen consumption in adipose tissue, improved insulin resistance, and decreased triglyceride storage. We conclude that FADD is a master regulator of glucose and fat metabolism with potential applications for treatment of insulin resistance and obesity. |
| format | Article |
| id | doaj-art-e70cdb2e805b45e7a77b0401ac41530c |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2016-06-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-e70cdb2e805b45e7a77b0401ac41530c2025-08-20T04:03:06ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842016-06-018889591810.15252/emmm.201505924FADD is a key regulator of lipid metabolismHongqin Zhuang0Xueshi Wang1Daolong Zha2Ziyi Gan3Fangfang Cai4Pan Du5Yunwen Yang6Bingya Yang7Xiangyu Zhang8Chun Yao9Yuqiang Zhou10Chizhou Jiang11Shengwen Guan12Xuerui Zhang13Jing Zhang14Wenhui Jiang15Qingang Hu16Zi‐Chun Hua17The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityChangzhou High‐Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc.The State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityThe State Key Laboratory of Pharmaceutical Biotechnology, College of Life Science and School of Stomatology, Affiliated Stomatological Hospital, Nanjing UniversityAbstract FADD, a classical apoptotic signaling adaptor, was recently reported to have non‐apoptotic functions. Here, we report the discovery that FADD regulates lipid metabolism. PPAR‐α is a dietary lipid sensor, whose activation results in hypolipidemic effects. We show that FADD interacts with RIP140, which is a corepressor for PPAR‐α, and FADD phosphorylation‐mimic mutation (FADD‐D) or FADD deficiency abolishes RIP140‐mediated transcriptional repression, leading to the activation of PPAR‐α. FADD‐D‐mutant mice exhibit significantly decreased adipose tissue mass and triglyceride accumulation. Also, they exhibit increased energy expenditure with enhanced fatty acid oxidation in adipocytes due to the activation of PPAR‐α. Similar metabolic phenotypes, such as reduced fat formation, insulin resistance, and resistance to HFD‐induced obesity, are shown in adipose‐specific FADD knockout mice. Additionally, FADD‐D mutation can reverse the severe genetic obesity phenotype of ob/ob mice, with elevated fatty acid oxidation and oxygen consumption in adipose tissue, improved insulin resistance, and decreased triglyceride storage. We conclude that FADD is a master regulator of glucose and fat metabolism with potential applications for treatment of insulin resistance and obesity.https://doi.org/10.15252/emmm.201505924FADDlipid metabolismobesityPPAR‐α |
| spellingShingle | Hongqin Zhuang Xueshi Wang Daolong Zha Ziyi Gan Fangfang Cai Pan Du Yunwen Yang Bingya Yang Xiangyu Zhang Chun Yao Yuqiang Zhou Chizhou Jiang Shengwen Guan Xuerui Zhang Jing Zhang Wenhui Jiang Qingang Hu Zi‐Chun Hua FADD is a key regulator of lipid metabolism EMBO Molecular Medicine FADD lipid metabolism obesity PPAR‐α |
| title | FADD is a key regulator of lipid metabolism |
| title_full | FADD is a key regulator of lipid metabolism |
| title_fullStr | FADD is a key regulator of lipid metabolism |
| title_full_unstemmed | FADD is a key regulator of lipid metabolism |
| title_short | FADD is a key regulator of lipid metabolism |
| title_sort | fadd is a key regulator of lipid metabolism |
| topic | FADD lipid metabolism obesity PPAR‐α |
| url | https://doi.org/10.15252/emmm.201505924 |
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