Peroxisome Proliferator-Activated Receptor Gamma Agonists
Modulate High-Fat Diet- and Carbon Tetrachloride-Induced
Non-Alcoholic Fatty Liver Disease Pathophysiology and
Transcriptional Expression of Inflammatory Markers in a Murine Model
Syeda Momna Ishtiaq1, Junaid Ali Khan1*, Faqir
Muhammad1 and Muhammad Shahid2
1Institute
of Physiology and Pharmacology, University of Agriculture,
Faisalabad-38040, Punjab, Pakistan
2Department
of Biochemistry, University of Agriculture, Faisalabad-38040,
Punjab, Pakistan
*Corresponding author:
junaidali.khan@uaf.edu.pk
Abstract
The objectives
of the present
study were to investigatethe effect of induced activation of peroxisome proliferator-activated
receptor gamma (PPARγ) through ligands, rosiglitazone (RG), kaempferol (KEM) and
GW9662 (GW) in pathophysiological
alterations
andinflammation by regulating the
expression of PPARγ-regulated genes in a rat model of nonalcoholic fatty liver
disease (NAFLD). Male wistar rats (N=45)were fed high fat diet (HFD; 35%) in combination with single dose of carbon
tetrachloride (CCl4; 0.5ml/kg/intraperitoneally)to induce NAFLD. The effects of synthetic PPARγ agonist; RG (15mg/kg) and
PPARγ antagonist; GW (10mg/kg) were evaluated in comparison with putative
natural ligand; KEM (12mg/kg). Co-administration of HFD and CCl4
mimicked NAFLD as evident by elevation of hepatic injury markers and lipid
profile in serum. The results of AST/ALT ratio and AST to platelet ratio index
indicated NAFLD without advanced liver disease. RG and KEM, in contrast to GW,
countered NAFLD-associated effects by ameliorating hepatic injury markers,
insulin resistance and lipid profile. KEM and RG treatment increased the
expression of IL-33, an anti-inflammatory cytokine, while the expression of
TNFα, a pro-inflammatory cytokine was non-significantly decreased. The results
suggested that PPARγ activation by agonist ligands might contribute towards
amelioration of NAFLD-associated pathophysiology of metabolic syndrome and
hepatic inflammation through regulation of IL-33 and TNFα.
To Cite This Article:
Ishtiaq SM, Khan JA, Muhammad F andShahid M, 2022.
Peroxisome proliferator-activated receptor gamma agonists modulate high-fat
diet- and carbon tetrachloride-induced non-alcoholic fatty liver disease
pathophysiology and transcriptional expression of inflammatory markers in a
murine model.
Pak Vet J, 42(3): 292-299. http://dx.doi.org/10.29261/pakvetj/2022.017