Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction

PLoS One. 2018 Dec 11;13(12):e0208396. doi: 10.1371/journal.pone.0208396. eCollection 2018.


Increase in saturated fatty acid (SFA) content in membrane phospholipids dramatically affects membrane properties and cellular functioning. We sought to determine whether exogenous SFA from the diet directly affects the degree of membrane phospholipid unsaturation in adult hearts and if these changes correlate with contractile dysfunction. Although both SFA-rich high fat diets (HFDs) and monounsaturated FA (MUFA)-rich HFDs cause the same degree of activation of myocardial FA uptake, triglyceride turnover, and mitochondrial FA oxidation and accumulation of toxic lipid intermediates, the former induced more severe diastolic dysfunction than the latter, which was accompanied with a decrease in membrane phospholipid unsaturation, induction of unfolded protein response (UPR), and a decrease in the expression of Sirt1 and stearoyl-CoA desaturase-1 (SCD1), catalyzing the conversion of SFA to MUFA. When the SFA supply in the heart overwhelms the cellular capacity to use it for energy, excess exogenous SFA channels to membrane phospholipids, leading to UPR induction, and development of diastolic dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomyopathies / metabolism*
  • Cardiomyopathies / pathology
  • Cells, Cultured
  • Diastole
  • Diet, High-Fat
  • Down-Regulation
  • Fatty Acids, Monounsaturated / analysis
  • Fatty Acids, Monounsaturated / metabolism
  • Male
  • Membrane Lipids / analysis
  • Membrane Lipids / metabolism*
  • Membranes / chemistry
  • Membranes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Myocardium / chemistry
  • Myocardium / metabolism
  • Phospholipids / analysis
  • Phospholipids / metabolism*
  • Triglycerides / analysis
  • Triglycerides / metabolism
  • Unfolded Protein Response / physiology


  • Fatty Acids, Monounsaturated
  • Membrane Lipids
  • Phospholipids
  • Triglycerides

Grants and funding

This work was supported by grants from the Japan Science and Technology Agency PRESTO to Motoaki Sano (2013-2015), the Japan Society for the Promotion of Science KAKENHI to Motoaki Sano (15H04825, 15H01160), to Tsunehisa Yamamoto (16K21358), and the Takeda Science Foundation to Tsunehisa Yamamoto. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.