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Molecules 2017, 22(7), 1062; doi:10.3390/molecules22071062

Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans

1,†
,
1,2,†
,
1,3
and
1,*
1
Key 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, China
2
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, China
3
School of Life Sciences, Anhui University, Hefei 230601, China
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 May 2017 / Accepted: 22 June 2017 / Published: 26 June 2017
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Abstract

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. View Full-Text
Keywords: calcineurin; tacrolimus; AMP-activated protein kinase (AMPK); triglyceride lipase ATGL; lipolysis calcineurin; tacrolimus; AMP-activated protein kinase (AMPK); triglyceride lipase ATGL; lipolysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wang, Y.; Xie, C.; Diao, Z.; Liang, B. Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans. Molecules 2017, 22, 1062.

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