Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans
Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanism...
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MDPI AG
2017-06-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/22/7/1062 |
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| author | Yanli Wang Cangsang Xie Zhiqing Diao Bin Liang |
| author_facet | Yanli Wang Cangsang Xie Zhiqing Diao Bin Liang |
| author_sort | Yanli Wang |
| collection | DOAJ |
| description | Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK) encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-12T04:43:03Z |
| publishDate | 2017-06-01 |
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| spelling | doaj.art-ffb96bd34dae47e698dbd06e2ba9ecf52022-12-22T03:47:34ZengMDPI AGMolecules1420-30492017-06-01227106210.3390/molecules22071062molecules22071062Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegansYanli Wang0Cangsang Xie1Zhiqing Diao2Bin Liang3Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, ChinaKey Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, ChinaCalcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK) encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents.http://www.mdpi.com/1420-3049/22/7/1062calcineurintacrolimusAMP-activated protein kinase (AMPK)triglyceride lipase ATGLlipolysis |
| spellingShingle | Yanli Wang Cangsang Xie Zhiqing Diao Bin Liang Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans Molecules calcineurin tacrolimus AMP-activated protein kinase (AMPK) triglyceride lipase ATGL lipolysis |
| title | Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans |
| title_full | Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans |
| title_fullStr | Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans |
| title_full_unstemmed | Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans |
| title_short | Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans |
| title_sort | calcineurin antagonizes ampk to regulate lipolysis in caenorhabditis elegans |
| topic | calcineurin tacrolimus AMP-activated protein kinase (AMPK) triglyceride lipase ATGL lipolysis |
| url | http://www.mdpi.com/1420-3049/22/7/1062 |
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