The Effect of Empagliflozin on Endoplasmic reticulum Stress in Fatty Liver Disease in Animal Model

Postgraduate Thesis uoadl:2898849 252 Read counter

Unit:
Κατεύθυνση Κλινική Χημεία
Library of the School of Science
Deposit date:
2020-03-06
Year:
2020
Author:
Papoutsi Aikaterini
Supervisors info:
Εύη Λιανίδου, Καθηγήτρια Αναλυτικής Χημείας - Κλινικής Χημείας, Τμήμα Χημείας, ΕΚΠΑ
Original Title:
Η Επίδραση της Εμπαγλιφλοζίνης στο Στρες του Ενδοπλασματικού Δικτύου στη Λιπώδη Διήθηση του Ήπατος σε Ζωικό Μοντέλο Μυός
Languages:
Greek
Translated title:
The Effect of Empagliflozin on Endoplasmic reticulum Stress in Fatty Liver Disease in Animal Model
Summary:
Non-alcoholic fatty liver disease is characterized by the accumulation of lipids in the liver and it is increasingly occurring in the population due to the adoption of bad eating habits. It is usually present in patients with type 2 diabetes mellitus and/or metabolic syndrome. SGLT2 inhibitors are a class of antidiabetic drugs that have been shown to have a positive effect on fatty infiltration.
In this study, we aimed to compare the effect of long-term and short-term administration of an SGLT2 inhibitor on parameters associated with non-alcoholic fatty liver disease. In particular, we investigated the effect of empagliflozin on diet-induced endoplasmic reticulum stress in the liver of ApoE (-/-) mice. Biochemical markers were measured at the onset and at the end of the interventions. The mRNA levels of genes that are involved in ER stress including eIF2α, ATF4, GRP78, CHOP, GRP94, Xbp1, IRE1 were measured by qPCR and the protein levels of eIF2α, p-eIF2α and CHOP by Western Blot. Liver sections were stained with H&E and histomorphometric analysis was performed. For both interventions (short-term and long-term), the results showed that there was a statistically significant reduction in fasting glucose and total cholesterol levels, but no significant changes were observed in LDL cholesterol and triglyceride levels compared to the control group. Histomorphometry indicated that long-term administration of empagliflozin significantly induced lipid accumulation and inflammation in liver, compared to Control group, while short-term administration reduced the concentration of hepatic lipids. The results from qPCR and Western Blot revealed that short-term administration of empagliflozin reduced gene expression of eIF2α, ATF4, GRP78, CHOP, GRP94, Xbp1 and IRE1 and protein expression of CHOP, eIF2α and eIF2α respectively (p≤0.05). In contrast, long-term administration significantly increased the levels of mRNA expression of GRP78, IRE1 and eIF2α (p≤0.05), while mRNA levels of Xbp1, GRP94, CHOP and ATF4 were also increased but not statistically significant. Western Blot results showed an increase in protein expression of eIF2α, p-eIF2α and CHOP with no statistical significance.
So, our study revealed that long-term administration of empagliflozin in ApoE (-/-) atherosclerosis mouse model promotes NAFLD and induces lipid accumulation and inflammation in the liver, at least partially via inducing the expression of genes involved in ER stress. In contrast, short-term administration of empagliflozin in the same animal model suppresses fatty infiltration and ER stress.
Main subject category:
Science
Keywords:
non-alcoholic fatty liver disease, sodium/glucose cotransporter 2 inhibitors, empagliflozin, fatty infiltration, endoplasmic reticulum stress
Index:
Yes
Number of index pages:
3
Contains images:
Yes
Number of references:
60
Number of pages:
117
Η Επίδραση της Εμπαγλιφλοζίνης στο Στρες του Ενδοπλασματικού Δικτύου στη Λιπώδη Διήθηση του Ήπατος σε Ζωικό Μοντέλο Μυός.pdf (3 MB) Open in new window