Research Information System
Şahin A. , Kartal Özer N. (Executive)
Project Supported by Higher Education Institutions, 2015 - 2017
Aim: The aim
of this study is to investigate the effect of varying oxysterol
levels on liver lipid metabolism and ER stress in NAFLD model of high
cholesterol diet, and the role of vitamin E in this process. Material and Methods: 24 male albino rabbits were assigned randomly
to 4 groups: 1) Control; normal rabbit chow 2) Cholesterol; 2% cholesterol containing
chow 3) Cholesterol+Vitamin E; 2% cholesterol food with daily i.m. injections
of vitamin E and 4) Vitamin E; normal food + daily i.m. injections of vitamin E.
After 8 weeks, blood samples and liver tissues were collected. Liver
tissues were examined macroscopically. In
sections obtained from high cholesterol fed rabbits liver tissues were
photographed NAFL formation with oil red staining and immunohistochemically
development of inflammation and steatosis with α-SMA, RAM11, col1A1 and 4HNE
markers on a light microscope. Endoplasmic reticulum stress (pIRE1, pPERK, Grp78 and Grp94),
lipid metabolism alteration (transcription factor of PPARα, PPARγ, SREBP1 and
SREBP2) and oxysterol-related (LXRα and ABCA1) proteins were determined by
immunoblotting technique. Oxysterol
levels were measured by LC-MS/MS using the MRM method. Results: Expression of pIRE1 and Grp94 protein
significantly increased in the hypercholesterolemic group, but significantly
decreased in the cholesterol + vitamin E group. While SREBP1, SREBP2 and PPARγ
expressions were increased in cholesterol group, these proteins were
significantly decreased in cholesterol + vitamin E group. LXRα decreased in
cholesterol group but ABCA1 was not change. While vitamin E administration was further
decreasing LXRα, ABCA1 expression significantly increased. Oxysterols; 24(S)-OHC,
25-OHC and 7-KC increased in cholesterol group, but no change were found for
27-OHC and 7α-OHC. While 24(S)-OHC, 25-OHC and 7-KC were significantly
decreased with vitamin E supplementation, 27-OHC and 7α-OHC were significantly
increased. Conclusion: Our results
suggest that NAFLD develped in high cholesterol fed rabbits by increased
accumulation of lipids in the liver, thus affects oxysterol levels, and that
varying levels of oxysterols play a role in triggering ER stress, and vitamin E
administration is thought to play a role in reducing NAFLD development in this
process.
Key Words: Non-alcoholic
fatty liver disease, oxysterol, ER stress