Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis
Accumulating evidence from both animal and human studies suggests that activation of beige fat increases cellular energy expenditure, ultimately reducing adiposity. Here, we report the central role of adipocyte-derived lysyl oxidase (Lox) in the formation of thermogenic beige fat. Mice exposed to co...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2022-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220301264 |
| _version_ | 1797728708216225792 |
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| author | Chun Xing Duo Jiang Yang Liu Qiqun Tang Haiyan Huang |
| author_facet | Chun Xing Duo Jiang Yang Liu Qiqun Tang Haiyan Huang |
| author_sort | Chun Xing |
| collection | DOAJ |
| description | Accumulating evidence from both animal and human studies suggests that activation of beige fat increases cellular energy expenditure, ultimately reducing adiposity. Here, we report the central role of adipocyte-derived lysyl oxidase (Lox) in the formation of thermogenic beige fat. Mice exposed to cold or a β3 agonist showed drastically lower Lox expression in thermogenically activated beige fat. Importantly, inhibition of Lox activity with BAPN stimulated biogenesis of beige fat in inguinal white adipose tissue (iWAT) under housing conditions and potentiated cold-induced adaptive thermogenesis and beiging in both iWAT and epididymal white adipose tissue (eWAT). Notably, white adipocytes with Lox repression undergo transdifferentiation into beige adipocytes which can be suppressed by tumor necrosis factor-α (TNFα) via ERK activation. This work provides new insight into the molecular control to expand beige fat by Lox inhibition and suggest the potential for utilizing inhibitor of Lox to treat the emerging epidemics of obesity and diabetes. |
| first_indexed | 2024-03-12T11:17:54Z |
| format | Article |
| id | doaj.art-a6f4be68763f4b3aa0dedf42c22bf8a6 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T11:17:54Z |
| publishDate | 2022-01-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Genes and Diseases |
| spelling | doaj.art-a6f4be68763f4b3aa0dedf42c22bf8a62023-09-02T01:48:04ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-01-0191140150Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesisChun Xing0Duo Jiang1Yang Liu2Qiqun Tang3Haiyan Huang4Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai 200032, PR ChinaKey Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai 200032, PR ChinaKey Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai 200032, PR ChinaKey Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai 200032, PR ChinaCorresponding author. Fax: +86 21 64033738.; Key Laboratory of Metabolism and Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University School of Basic Medical Sciences, Shanghai 200032, PR ChinaAccumulating evidence from both animal and human studies suggests that activation of beige fat increases cellular energy expenditure, ultimately reducing adiposity. Here, we report the central role of adipocyte-derived lysyl oxidase (Lox) in the formation of thermogenic beige fat. Mice exposed to cold or a β3 agonist showed drastically lower Lox expression in thermogenically activated beige fat. Importantly, inhibition of Lox activity with BAPN stimulated biogenesis of beige fat in inguinal white adipose tissue (iWAT) under housing conditions and potentiated cold-induced adaptive thermogenesis and beiging in both iWAT and epididymal white adipose tissue (eWAT). Notably, white adipocytes with Lox repression undergo transdifferentiation into beige adipocytes which can be suppressed by tumor necrosis factor-α (TNFα) via ERK activation. This work provides new insight into the molecular control to expand beige fat by Lox inhibition and suggest the potential for utilizing inhibitor of Lox to treat the emerging epidemics of obesity and diabetes.http://www.sciencedirect.com/science/article/pii/S2352304220301264Adaptive thermogenesisBATBeige fatLysyl oxidaseTNFα |
| spellingShingle | Chun Xing Duo Jiang Yang Liu Qiqun Tang Haiyan Huang Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis Genes and Diseases Adaptive thermogenesis BAT Beige fat Lysyl oxidase TNFα |
| title | Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| title_full | Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| title_fullStr | Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| title_full_unstemmed | Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| title_short | Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| title_sort | lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis |
| topic | Adaptive thermogenesis BAT Beige fat Lysyl oxidase TNFα |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220301264 |
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