Low-Level Saturated Fatty Acid Palmitate Benefits Liver Cells by Boosting Mitochondrial Metabolism via CDK1-SIRT3-CPT2 Cascade

Lin Liu, Bowen Xie, Ming Fan, Demet Candas-Green, Joy X. Jiang, Ryan Wei, Yinsheng Wang, Hong Wu Chen, Yiyang Hu, Jian Jian Li

Research output: Contribution to journalArticle

Abstract

Saturated fatty acids (SFAs) (the “bad” fat), especially palmitate (PA), in the human diet are blamed for potential health risks such as obesity and cancer because of SFA-induced lipotoxicity. However, epidemiological results demonstrate a latent benefit of SFAs, and it remains elusive whether a certain low level of SFAs is physiologically essential for maintaining cell metabolic hemostasis. Here, we demonstrate that although high-level PA (HPA) indeed induces lipotoxic effects in liver cells, low-level PA (LPA) increases mitochondrial functions and alleviates the injuries induced by HPA or hepatoxic agent carbon tetrachloride (CCl4). LPA treatment in mice enhanced liver mitochondrial activity and reduced CCl4 hepatotoxicity with improved blood levels of aspartate aminotransferase (AST), alanine transaminase (ALT), and mitochondrial aspartate transaminase (m-AST). LPA-mediated mitochondrial homeostasis is regulated by CDK1-mediated SIRT3 phosphorylation, which in turn deacetylates and dimerizes CPT2 to enhance fatty acid oxidation. Thus, an advantageous effect is suggested by the consumption of LPA that augments mitochondrial metabolic homeostasis via CDK1-SIRT3-CPT2 cascade.

Original languageEnglish (US)
Pages (from-to)196-209.e9
JournalDevelopmental Cell
Volume52
Issue number2
DOIs
StatePublished - Jan 27 2020

Keywords

  • CCl
  • CDK1
  • CPT2
  • fatty acid oxidation
  • hepatotoxicity
  • metabolism
  • mitochondria
  • palmitate
  • saturated fatty acid
  • SIRT3

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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