A dipeptidyl peptidase IV inhibitory peptide relieves palmitic acid-induced endoplasmic reticulum stress in HepG2 cells independent of inhibiting dipeptidyl peptidase IV activity

  • Food Funct. 2021 Nov 1;12(21):10773-10782. doi: 10.1039/d1fo02283k.
Ritian Jin  1  2  3 ,  Haowei Ren  1  2  3 ,  Minhe Liao  1  2  3 ,  Jiaqi Shang  1  2  3 ,  Dangfeng Wang  4  5 ,  Meng Li  1  2 ,  Ning Liu  1  2  3
Affiliations
  • 1. College of Food Science, Northeast Agricultural University, Harbin, 150030, China. [email protected].
  • 2. Key Lab of Dairy Science, Ministry of Education, Northeast Agricultural University, Harbin, 150030, China.
  • 3. Harbin Tengning Technology Co., Ltd, Harbin, 150010, China.
  • 4. College of Food Science and Technology, Bohai University, Food Safety Key Lab of Liaoning Province, National & Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Jinzhou, Liaoning, 121013, China.
  • 5. College of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.
PMID: 34609396 DOI: 10.1039/d1fo02283k
Abstract

The peptide VLATSGPG (VLA) is known to inhibit Dipeptidyl Peptidase IV (DPP-IV), although its mechanism in relieving endoplasmic reticulum (ER) stress is unclear. In this study, we found that treating HepG2 cells with 1.0 mM VLA reduced DPP-IV activity by 73.7 ± 4.8% without changing the DPP-IV mRNA expression level. In addition, 1.0 and 0.5 mM VLA alleviated palmitic acid (PA)-induced cell death and intracellular calcium imbalances. The levels of apoptosis-related proteins (Caspase-3, caspase-9, and CHOP) were reduced by VLA treatment, which was presumed to be related to ER stress. Further studies confirmed that VLA alleviated PA-induced morphological damage to the ER and reduced the levels of the ER stress marker proteins (BIP, p-PERK, and p-IRE1α). VLA alleviated PA-induced ER stress in HepG2 cells independent of DPP-IV enzymatic activity inhibition. These findings have implications for developing novel treatment approaches for liver diseases caused by ER stress.

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