Sulforaphane improves abnormal lipid metabolism via both ERS-dependent XBP1/ACC &SCD1 and ERS-independent SREBP/FAS pathways

Sicong Tian, Baolong Li, Peng Lei, Xiuli Yang, Xiaohong Zhang, Yongping Bao, Yujuan Shan

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Abstract

Scope: To investigate the effect of sulforaphane (SFN) on the abnormal lipid metabolism and underlying mechanisms. 
Methods and results: Models with abnormal lipid metabolism were established both in rats and human hepatocytes. Hepatic steatosis was detected by H&E and oil red O staining. The structure of endoplasmic reticulum was visualized by transmission electron microscopy. The expressions of X-box binding protein 1 (XBP1), protein kinase-like ER kinase (PERK), sterol regulatory element binding protein-1c (SREBP1c) and lipogenic enzymes were determined by real-time PCR and western blot analysis. SFN lowered the content of triglyceride and cholesterol. SFN alleviated the swelling of endoplasmic reticulum (ER) and decreased the perimeter of ER. SFN significantly decreased the expressions of acetyl CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase 1 (SCD1) and fatty acid synthase. SFN inhibited SREBP1c by blocking the PERK. Meanwhile, SFN suppressed ACC1 and SCD1 via blocking the formation of splicing-type XBP1. The key roles of XBP1 and SREBP1c in SFN-reduced lipid droplets were confirmed by a timed sequence of measurement according to time points. 
Conclusion: SFN improved abnormal lipid metabolism via both ER stress -dependent and -independent pathways.
Original languageEnglish
Article number1700737
JournalMolecular Nutrition & Food Research
Volume62
Issue number6
Early online date23 Feb 2018
DOIs
Publication statusPublished - Mar 2018

Keywords

  • endoplasmic reticulum stress
  • lipid metabolism
  • lipogenic enzymes
  • sterol regulatory element binding protein-1C
  • sulforaphane

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