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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:


The objectives of the present study were to investigate the effect of induced activation of peroxisome proliferator-activated receptor gamma (PPARγ) through ligands, rosiglitazone (RG), kaempferol (KEM) and GW9662 (GW) in pathophysiological alterations and inflammation 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 and Shahid 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.


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