Saroglitazar improved hepatic steatosis and fibrosis by modulating inflammatory cytokines and adiponectin in an animal model of non-alcoholic steatohepatitis

• Published in: BMC pharmacology & toxicology 2021-10, Vol.22 (1), p.53-9, Article 53
• Main Authors: Akbari, Rasoul, Behdarvand, Tahereh, Afarin, Reza, Yaghooti, Hamid, Jalali, Mohammad Taha, Mohammadtaghvaei, Narges
• Format: Article
• Language: English
• Subjects: Adiponectin; Agonists; Alanine Transaminase - blood; Animal models; Animals; Apoptosis; Aspartate Aminotransferases - blood; Body fat; Body weight; Bone morphogenetic proteins; Cytokines; Cytokines - genetics; Disease Models, Animal; Enzymes; Fatty acids; Fatty liver; Fenofibrate; Fibrosis; Gene expression; Gene Expression Regulation - drug effects; Global health; Growth factors; Inflammation; Insulin resistance; Interleukin 6; Interleukins; Laboratory animals; Leptin; Lipids; Liver; Liver - drug effects; Liver - pathology; Liver Cirrhosis - blood; Liver Cirrhosis - drug therapy; Liver Cirrhosis - genetics; Liver Cirrhosis - pathology; Liver diseases; Male; MCP-1; Medical research; Metabolic disorders; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; NASH; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - pathology; Oxidative stress; Peroxisome proliferator-activated receptors; Phenylpropionates - pharmacology; Phenylpropionates - therapeutic use; Pioglitazone; PPAR alpha - agonists; PPAR gamma - agonists; PPAR- α/γ; Public health; Pyrroles - pharmacology; Pyrroles - therapeutic use; Rats; Rats, Wistar; Saroglitazar; Serum levels; Steatosis; TGF-β; TNF- α; Transforming growth factor-b; Transforming growth factors; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Variance analysis; World health
• ISSN: 2050-6511; 2050-6511
• DOI: 10.1186/s40360-021-00524-8

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have become significant global health concerns. In the present study, we aimed to investigate the effects of saroglitazar, a dual PPARα/γ agonist, fenofibrate, a PPAR-α agonist, and pioglitazone, a PPAR-γ agonist on an animal model of NASH. Male Wistar rats were fed a high-fat (HF) emulsion via gavage for 7 weeks to induce NASH. The HF-treated rats were grouped into four groups to receive saroglitazar, pioglitazone, fenofibrate, or vehicle. We measured body and liver weight, liver enzymes, serum levels of adiponectin and leptin. We also performed histopathological examinations and gene expression analysis of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF- α), transforming growth factor-beta (TGF-β), and monocyte chemoattractant protein 1 (MCP-1). Body weight was markedly normalized by both saroglitazar and fenofibrate, while the liver index only decreased significantly with saroglitazar. Saroglitazar corrected ALT, AST, leptin, and adiponectin levels better than pioglitazone and fenofibrate. All PPAR agonists significantly attenuated the upregulation of the proinflammatory and TGF-β genes, which correlated with the improved steatosis, inflammation of liver tissue, and fibrotic lesions. As documented by our results, the dual activation of PPARα/γ by saroglitazar could effectively improve steatosis, fibrosis, and aspects of necro-inflammation in the HF-induced NASH model more than fenofibrate and pioglitazone, and it can be more beneficial in the management of NASH.