Open Access

Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders

  • Authors:
    • Zhi-Sen Pan
    • Yan-Ling Chen
    • Kai-Jia Tang
    • Zhang-Zhou Liu
    • Jia-Li Liang
    • Yan-Hao Guan
    • Xiao-Yi Xin
    • Chang-Hui Liu
    • Chuang-Peng Shen
  • View Affiliations

  • Published online on: May 15, 2023     https://doi.org/10.3892/etm.2023.12019
  • Article Number: 320
  • Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pachymic acid (Pac), a major bioactive constituent of Poria cocos, is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)‑palmitic acid (PA)‑induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver‑specific SIRT6‑deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA‑induced lipid deposition in MPHs in a dose‑dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA‑incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA‑induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA‑induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.
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July-2023
Volume 26 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Pan Z, Chen Y, Tang K, Liu Z, Liang J, Guan Y, Xin X, Liu C and Shen C: Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders. Exp Ther Med 26: 320, 2023.
APA
Pan, Z., Chen, Y., Tang, K., Liu, Z., Liang, J., Guan, Y. ... Shen, C. (2023). Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders. Experimental and Therapeutic Medicine, 26, 320. https://doi.org/10.3892/etm.2023.12019
MLA
Pan, Z., Chen, Y., Tang, K., Liu, Z., Liang, J., Guan, Y., Xin, X., Liu, C., Shen, C."Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders". Experimental and Therapeutic Medicine 26.1 (2023): 320.
Chicago
Pan, Z., Chen, Y., Tang, K., Liu, Z., Liang, J., Guan, Y., Xin, X., Liu, C., Shen, C."Pachymic acid modulates sirtuin 6 activity to alleviate lipid metabolism disorders". Experimental and Therapeutic Medicine 26, no. 1 (2023): 320. https://doi.org/10.3892/etm.2023.12019