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Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism

Author

Listed:
  • Yoon Keun Cho

    (Seoul National University)

  • Young Cheol Yoon

    (Seoul National University)

  • Hyeonyeong Im

    (Seoul National University)

  • Yeonho Son

    (Seoul National University)

  • Minsu Kim

    (Seoul National University)

  • Abhirup Saha

    (Seoul National University)

  • Cheoljun Choi

    (Seoul National University)

  • Jaewon Lee

    (Seoul National University)

  • Sumin Lee

    (Seoul National University)

  • Jae Hyun Kim

    (Kangwon National University)

  • Yun Pyo Kang

    (Seoul National University)

  • Young-Suk Jung

    (Pusan National University)

  • Hong Koo Ha

    (Pusan National University)

  • Je Kyung Seong

    (Seoul National University)

  • James G. Granneman

    (Wayne State University)

  • Sung Won Kwon

    (Seoul National University)

  • Yun-Hee Lee

    (Seoul National University)

Abstract

Dysregulation of adipose tissue plasmalogen metabolism is associated with obesity-related metabolic diseases. We report that feeding mice a high-fat diet reduces adipose tissue lysoplasmalogen levels and increases transmembrane protein 86 A (TMEM86A), a putative lysoplasmalogenase. Untargeted lipidomic analysis demonstrates that adipocyte-specific TMEM86A-knockout (AKO) increases lysoplasmalogen content in adipose tissue, including plasmenyl lysophosphatidylethanolamine 18:0 (LPE P-18:0). Surprisingly, TMEM86A AKO increases protein kinase A signalling pathways owing to inhibition of phosphodiesterase 3B and elevation of cyclic adenosine monophosphate. TMEM86A AKO upregulates mitochondrial oxidative metabolism, elevates energy expenditure, and protects mice from metabolic dysfunction induced by high-fat feeding. Importantly, the effects of TMEM86A AKO are largely reproduced in vitro and in vivo by LPE P-18:0 supplementation. LPE P-18:0 levels are significantly lower in adipose tissue of human patients with obesity, suggesting that TMEM86A inhibition or lysoplasmalogen supplementation might be therapeutic approaches for preventing or treating obesity-related metabolic diseases.

Suggested Citation

  • Yoon Keun Cho & Young Cheol Yoon & Hyeonyeong Im & Yeonho Son & Minsu Kim & Abhirup Saha & Cheoljun Choi & Jaewon Lee & Sumin Lee & Jae Hyun Kim & Yun Pyo Kang & Young-Suk Jung & Hong Koo Ha & Je Kyun, 2022. "Adipocyte lysoplasmalogenase TMEM86A regulates plasmalogen homeostasis and protein kinase A-dependent energy metabolism," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31805-3
    DOI: 10.1038/s41467-022-31805-3
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    References listed on IDEAS

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    1. Florian Wagner, 2015. "GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-26, November.
    2. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
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    1. Cheoljun Choi & Yujin L. Jeong & Koung-Min Park & Minji Kim & Sangseob Kim & Honghyun Jo & Sumin Lee & Heeseong Kim & Garam Choi & Yoon Ha Choi & Je Kyung Seong & Sik Namgoong & Yeonseok Chung & Young, 2024. "TM4SF19-mediated control of lysosomal activity in macrophages contributes to obesity-induced inflammation and metabolic dysfunction," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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