1. Academic Validation
  2. CKIP-1 augments autophagy in steatotic hepatocytes by inhibiting Akt/mTOR signal pathway

CKIP-1 augments autophagy in steatotic hepatocytes by inhibiting Akt/mTOR signal pathway

  • Exp Cell Res. 2020 Dec 1;397(1):112341. doi: 10.1016/j.yexcr.2020.112341.
Li Li 1 Ping Xie 2 Wenjun Lin 1 Jinsheng Liu 3 Jing Chen 1 Zihao Guo 1 Chuxuan Bin 1 Wei An 4 Chuan Zhang 5 Yutao Zhan 6
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
  • 2 Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, 100069, China.
  • 3 Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
  • 4 Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing, 100069, China. Electronic address: anwei@ccmu.edu.cn.
  • 5 Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. Electronic address: digestivezhang@163.com.
  • 6 Department of Gastroenterology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China. Electronic address: yutaozhan@263.net.
Abstract

Nonalcoholic fatty liver disease (NAFLD), which is characterized by aberrant accumulation of intrahepatic triglycerides and lipid droplets (LDs) in the liver cells, is becoming increasingly prevalent at an alarming rate worldwide. LDs can be consumed by either hydrolysis or Autophagy, which is shown to be of importance in the regulation of hepatic lipid metabolism. We have shown that deficiency of pleckstrin homology domain-containing Casein Kinase 2 interacting protein-1 (CKIP-1), a scaffold protein that interacts with various proteins in multiple signal pathways, in mice aggravates high-fat diet induced fatty liver. However, its underlying mechanisms remain largely unknown. In this study, we found that the mRNA and protein levels of CKIP-1 decreased dramatically in steatotic HepG2 cells induced by oleic acid (OA) treatment. Coincidently, hepatic Autophagy was also dynamically regulated in steatotic HepG2 cells. In addition, overexpression of CKIP-1 activated Autophagy by suppression of Akt/mTOR signaling, which in turn reduced lipid accumulation. Moreover, these phenomena were reversed in CKIP-1-shRNA transfected steatotic hepatocytes. To further evaluate the potential role of CKIP-1 in Autophagy, we determined the level of Autophagy related proteins in CKIP-1 knockout mice. These results supported our findings in vitro. In summary, we found CKIP-1 to be a positive regulator of hepatic Autophagy and a promising therapeutic target for treatment of NAFLD.

Keywords

Akt/mTOR signal pathway; Autophagy; Casein kinase 2 interacting protein-1 (CKIP-1); Nonalcoholic fatty liver disease (NAFLD).

Figures
Products